Ministry of Health, Labour and Welfare Clinical Research Grant for
Work-related Injuries and Illness

Epidemiological Study of Health Eﬀects inFukushima Nuclear Emergency Workers(Epidemiological study on emergency workers at TEPCO Fukushima Daiichi Nuclear Power Plant)

Phase 2 (FY 2019 - FY 2023)

Third-Party Evaluation Committee Report

Chairperson Ginji Endo

March 2023

TABLE OF CONTENTS
Introduction .......................................................................................................................... 57◆Third-Party Evaluation Committee Report
Chapter I

Evaluation for the Second Phase Study

1. Securing of study participants, research implementation system, and healthinvestigation results . ..................................................................................................... 59
2. Scientific evaluation
1) Baseline survey .......................................................................................................... 60
2) Statistical power and analytical methods .................................................................. 61
3) Dose evaluation ......................................................................................................... 64
4) Investigation of cause of death .................................................................................. 66
5) Cancer morbidity investigation ................................................................................. 66
6) Thyroid cancer investigation . ................................................................................... 67
7) Cataract investigation ............................................................................................... 68
8) Psychological impact investigation ........................................................................... 69
9) Health management database ................................................................................... 70
Chapter II

Suggestions for the Third Phase Study

1) Research management structure ............................................................................... 71
2) Follow-up of the cohort and subcommittee and study organization ......................... 71
3) Statistical power and analytical methods .................................................................. 75
4) Dose evaluation ......................................................................................................... 76
5) Investigation of cause of death .................................................................................. 76
6) Cancer morbidity investigation ................................................................................. 76
7) Thyroid cancer investigation . ................................................................................... 778) Cataract investigation ............................................................................................... 78
9) Psychological impact investigation ........................................................................... 78
10) Health management database ................................................................................. 79
Chapter III

Evaluation of the Second Phase Study and Suggestions for the Third Phase
Study [Summary] ............................................................................................ 80

Attachment: Research management structure ...................................................................... 85◆Headquarters and Sub-Investigation Committee Reports
1. Epidemiological Survey Headquarters .............................................................................. 87
2. The Clinical Investigation Subcommittee (I) ................................................................... 90
3. The Clinical Investigation Subcommittee (II) .................................................................. 94
4. The Analysis and Evaluation Subcommittee . ................................................................. 100
5. The Radiation Dose Evaluation Subcommittee .............................................................. 103
6. The Cause of Death/Cancer Morbidity Investigation Subcommittee ............................ 107
7. The Thyroid Cancer Investigation Subcommittee . ........................................................ 112
8. The Cataract Investigation Subcommittee ..................................................................... 116
9. The Psychological Impact Subcommittee ....................................................................... 120
10. The Health Management Database Subcommittee ...................................................... 122

Introduction
The Epidemiological Study of Health Effects in Fukushima Nuclear Emergency Workers was
initiated at the National Institute for Occupational Safety and Health, Japan in 2019, with thesupport of a clinical research grant from the Ministry of Health, Labour and Welfare (MHLW)
for work-related injuries and illness.
This study aims to conduct a long-term follow-up investigation on approximately 20,000
emergency workers who were involved in the response to the Tokyo Electric Power Company's
Fukushima Daiichi Nuclear Power Plant accident, which occurred in March 2011. The study
seeks to elucidate the health effects of radiation exposure and other related factors throughout
their lifetimes.
Based on the guidelines of the research grant, which stipulate the need to establish
an independent committee (the third-party committee) comprising researchers withinternationally recognized expertise, and to receive evaluation from an international
standpoint, we formed a third-party committee in 2022. The committee consisted of experts
recommended by relevant academic societies and was tasked with evaluating the study
conducted from 2019 onwards. Committee meetings were held as follows.
At the committee meetings, the research team's progress reports were presented by theheadquarters and co-investigators. These reports were thoroughly examined and discussed
under the leadership of the committee chair, who was elected through mutual selection. The
committee worked independently to compile this report, ensuring its originality and integrity.
Lastly, we sincerely thank Prof. Ginji Endo for serving as the Chairperson of the ThirdParty Committee and Prof. Masayuki Tatemichi for his invaluable contributions as Deputy
Chairperson in compiling this report. We are also grateful to all the committee members fortheir valuable and accurate opinions.
Date and time of the Third-Party Evaluation Committee meetings
The 1st meeting 13:30-17:30 on Monday, Nov. 28, 2022 at FUKURACIA Yaesu Tokyo
The 2nd meeting 13:30-17:30 on Wednesday, Dec. 7, 2022 at FUKURACIA Yaesu Tokyo
The 3rd meeting 13:30-17:30 on Monday, Feb. 20, 2023 at FUKURACIA Yaesu Tokyo
List of Third-Party Evaluation Committee Members
Hirotsugu Ueshima
Ginji Endo*

Specially Appointed Professor, NCD Epidemiology ResearchCenter, Shiga University of Medical Science

Director, Osaka Occupational Health Service Center, Japan
Industrial Safety & Health Association−57−

Kazuyuki Omae

Professor Emeritus, Keio University

Michiaki Kai

Professor, Nippon Bunri University

Takashi Kitaoka

Professor, Department of Ophthalmology and Visual Sciences,
Graduate School of Biomedical Sciences, Nagasaki University

Kazuo Sakai

Director, Radiation Effects Association

Gen Suzuki

Director, International University of Health and Welfare Clinic

Masayuki Tatemichi**Akizumi Tsutsumi

Professor, Department of Preventive Medicine, Tokai
University School of Medicine

Professor, Department of Public Health, Kitasato University
School of Medicine

Center for Cancer Registries, National Cancer Center InstituteTakahiro Higashi

for Cancer Control

Professor, Department of Public Health, School of Medicine,
The University of Tokyo*: Chairperson, **: Deputy Chairperson
March 31, 2023
National Institute of Occupational Safety and Health, Japan
Director of the Research Center for Prevention from Radiation Hazards of Workers“Epidemiological Study of Health Effects in Fukushima Nuclear Emergency Workers ”
Toshiteru Okubo / Principal Investigator−58−

Third-Party Evaluation Committee Report
Chapter I

Evaluation for the Second Phase Study

1. Securing of study participants, research implementation system, and health investigation
results
In the Epidemiological Study of Health Effects in Fukushima Nuclear Emergency Workers(NEWS), the cumulative number of study participants reached 8,023 of the study population(n=19,812) in 6 years from the start of the study, and the cumulative number of workers who
received health examinations reached 6,286, which should be highly evaluated as the effortof researchers.
The handover of operations associated with the transfer of the principal investigator ofthis study (Toshiteru Okubo) from the Radiation Effects Research Foundation (RERF) to
the National Institute of Occupational Safety and Health, Japan (JNIOSH), began withthe transfer of data collected in the first phase (paper documents, electromagnetic records,
and electromagnetic recording media). The task must have required considerable effort andattention, particularly in ensuring privacy protection. Subsequently, the study made use of
the experience gained from previous follow-up surveys conducted on A-bomb survivors at
RERF to recruit participants through a postal survey and obtain their consent for the study.
The study organization, including the researchers, made significant efforts that allowed thestudy to continue smoothly throughout the first and second phases.
The addresses and other personal information of the study participants are provided
annually from the database created and maintained by the government with cooperation ofTokyo Electric Power Co., Ltd. (TEPCO). However, in this study, we also obtain individual
information, such as address changes, through the epidemiological survey, resulting in a time
lag in the information and causing difficulties in contacting the participants directly. For
instance, it has been observed that on multiple occasions, after an individual has notified one
organization of a change in address, another organization contacts the old address before theinformation is provided. Having multiple databases for the same individual is not desirable
for the progress of this type of research, and database sharing is recommended.
The researchers made continuous efforts to recruit participants through various methods,
in addition to the mail survey, and the results are evaluated positively. Although there was adecrease in the number of cooperating health examination institutions, the attempt to secure
the number of examinees through new initiatives, such as the headquarters-sponsoredintensive examinations, is commendable.
The accuracy of laboratory measurement has been improved recently, especially in the−59−nationwide laboratories. Therefore, we agree that the method of consolidating analyticalwork at a single laboratory, which has been conducted so far, may have diminished significanceregarding general laboratory test items considering the advantages and disadvantagesof workload and the time difference due to long-distance transportation. However, it isdesirable that examination items specific to radiation hazards and diagnostic imaging should
be consolidated under the supervision of the principal investigator and managed under thesame conditions. Particularly for images, since differences due to the devices and radiologists
cannot be ignored, it is preferable to manage and store them as electronic data (or film data)
under the supervision of the principal investigator.
2. Scientific evaluation
1) Baseline survey
In the baseline survey, which included 6,031 participants as of December 31, 2022, therelationship between socioeconomic status, lifestyle habits, and the radiation exposure
dose (mSv) during emergency operations was analyzed. To examine the causal relationshipbetween the exposure dose and future disease incidence, mortality, etc., it is crucial toconsider the presence of any differences in basic attributes in relation to radiation exposure
doses, identify potential confounding factors, and understand methods of controlling them.
In this regard, it was revealed that the mean age in the group with the highest exposure
dose ( > 100 mSv) was younger by 2.8 years than the overall mean age (52.2 years). In
the ≥ 100 mSv group, the percentage of TEPCO workers was significantly high at 85.2%,
surpassing the overall percentage of 37%. The characteristic of younger age suggests a
potential association with a lower prevalence of hypertension, diabetes, and cardiovasculardisease, as indicated by the questionnaire, compared to the lower exposure dose groups.
On the other hand, the characteristic of a higher proportion of TEPCO workers is likely to
be associated with a high frequency of medical examinations and a higher detection rate of
disease findings. Specifically, it appears to be related to a higher rate of reporting cataract
and thyroid diseases as past medical history in the questionnaire.
Furthermore, the mean age in the group with a high exposure dose (50-99 mSv) was
younger by 1.9 years than the overall mean age. At the same time, it appeared to be associatedwith a lower proportion of individuals with a college degree or higher education, a higher
marriage rate, a higher prevalence of individuals engaged in leisure-time physical activities,
a higher alcohol consumption rate, and a lower smoking rate.
The analysis based on the results of the baseline survey, including the analysis of otheritems, clearly demonstrates the need for thorough consideration in studying the causal
relationship between exposure dose and the onset of diseases in the future.

−60−2) Statistical power and analytical methods
According to the estimation of statistical power in the first phase, assuming a total of 7,200
study participants and using the calculation of 7,200 × 40 years = 288,000 person-years, it
was determined that even with 40 years of follow-up, the study could not achieve a statisticalpower of 80% to detect a 10% increase in cancer incidence due to radiation exposure, basedon the risk estimate from the epidemiological study of A-bomb survivors. Therefore, it was
concluded that in order to detect the effects of radiation, it would be necessary to follow up
with all participants (approximately 20,000 individuals) for over 40 years. Subsequently,
in the second phase, the statistical power calculation was reassessed for different cancer
types, including thyroid cancer, based on recommendations from the Third-Party Evaluation
Committee.
The power calculation in the second phase showed that with a 40-year follow-up, thestatistical power would be at most around 10% for any type of cancer. It was concluded
that with an extension of the follow-up period from 20 years to 40 years and a doubling of
the expected number of participants, the increase in statistical power would be only a few
percent for cancers in any tissue, and no substantial improvement would be expected.
A number of assumptions are used in the power calculation, and changes in theseassumptions can impact the results of the calculation. For the assumption of excess relativerisk (ERR) of radiation at low doses, calculations of higher ERRs (from 2 to 10 fold) thanpreviously reported have been reported. For overall cancer and thyroid cancer, it has beensuggested that a ERR more than 5 times higher would be detectable. For thyroid cancer,
the ERRs from the reported epidemiological survey of Chernobyl decontamination workers
were used. The Chernobyl survey included screening of the thyroid gland, and the effects
of its overdiagnosis and the effects of insufficient stable iodine intake may have biased the
ERR estimates. The ERR value of 3.8 per Gy used in the calculation of statistical power
for thyroid cancer is higher than the ERR estimated in the A-bomb studies. In studiesof A-bomb survivors, the risk of thyroid cancer due to exposure in adulthood is barely
detectable in analyses that exclude thyroid microcarcinoma (Furukawa et al. Int. J. Cancer:
132, 1222-1226 [2013]).
On the other hand, an analysis focusing on latent thyroid cancer and nodules revealed
a significant correlation with radiation dose (Ezaki et al. https://doi.org/10.1269/jrr.32.
SUPPLEMENT_193). When ultrasound screenings are performed, they can detect microcancers. This presents the potential to detect the presence or absence of radiation effects
on thyroid cancer that were not previously included in the analysis as either micro-cancers
or latent cancers. Reassessment of the statistical power is necessary. However, calculating
the statistical power without considering the influence of confounding factors may lead to−61−

overestimation. At the very least, for lung cancer, it is necessary to calculate the statisticalpower by taking into account the effect of smoking.
Among the emergency workers, there is a group that has been exposed to high levelsof thyroid radiation due to inhalation of radioactive iodine. Therefore, it may be useful
information for future epidemiological studies to estimate the thyroid dose and calculate thestatistical power to detect not only thyroid cancer but also benign thyroid diseases that aresuggested to have a high radiation sensitivity.
It is theoretically impossible to prove the absence of radiation effects throughepidemiological studies. This power calculation conducted in this study demonstrated thechallenges of verifying the risk estimation values reported in epidemiological studies ofA-bomb survivors. However, despite the limitations in statistical power, this study stands
out from large-scale epidemiological studies conducted internationally through its highquality dosimetry measurements and comprehensive investigation of confounding factors.
Leveraging the characteristics of this cohort, similar to the Japanese epidemiological study
on low-dose radiation effects (J-EPISODE) (Kudo et al., Health Phys. 2022), it holds greatsignificance to disseminate evidence-based information from a perspective of worker healthmanagement. This includes the message that improving lifestyle habits can lead to risk
reduction, which goes beyond radiation risks. Further analysis in this regard is expected in
the future.
Based on the detailed power calculation, it is unlikely that sufficient power can be obtainedat present to detect the assumed effects of radiation, even with long-term follow-up for allparticipants. Therefore, it seems to be impossible to prove the absence of radiation effects
from the emergency operations in this accident. Moreover, calculating a significant ERR
large enough to indicate an effect, based on previous findings, is also unlikely. Therefore,
careful consideration should be given to how the analysis results will be interpreted andcommunicated to society. One approach is to interpret the P-value according to its original
meaning and explain that it represents the probability of observing the current values (orvalues more extreme than them) when it is true that there is no radiation effect (i.e., thenull hypothesis is correct). Alternatively, a range of options should be considered, such asreporting the probability of observing a value when a socially acceptable value (e.g., ERR=X
due to lack of exercise) is true. Nevertheless, it is important to acknowledge that interpretingand communicating these findings may be challenging. Given this situation, although it may
extend beyond the role of analysis evaluation, it may be necessary to prepare knowledge
about methods for risk communication in relation to the overall direction.
A significant role of the research team is to investigate the relationship between radiation
exposure and the risk of developing cancer. However, unfortunately, the Analysis and−62−

Evaluation Subcommittee (Shinji Yoshinaga) has pointed out the limited statistical power
due to the small target population and sample size. Therefore, another important investigationis the relationship between radiation exposure and non-cancer diseases, specifically thedeterministic effects expressed by prevalence. There are a large number of participants,
and there are survey items that can be conducted on the entire population. If there is acausal relationship with radiation exposure, it is believed that a sufficient sample size can beobtained. Therefore, it is important to clarify the survey methods for individuals with noncancer diseases and the measurement techniques, and conduct a fundamental examination
to determine which indicators should be used to control the confounding bias in the analysisof the relationship between radiation exposure and non-cancer diseases.
The objective of the Clinical Investigation Subcommittee (II) is to identify the potential
confounding factors in this population for future epidemiological studies that will examine
the association between radiation exposure and the risk of cancer and non-cancer diseases.
From this perspective, the following two objectives listed for this subcommittee's research
are appropriate.
①

To elucidate the health impacts of social factors including employment and living
background, as well as health management conditions such as industrial health andhealthcare environment, on emergency workers.

②

To provide information that enables understanding of the social background of
emergency workers, which is necessary for study evaluation, health examinations, andpost-guidance.

As the outcomes in the second phase, significant associations were observed between
educational background and systolic blood pressure, white blood cell count, HbA1c, γGTP,
and other factors. Even after adjusting for age, an inverse association was observed between
educational background and smoking rates and alcohol drinking habit. Similarly, a reverse
association was observed between annual income and smoking rates. These results support
the general hypothesis that higher education is associated with higher health literacy,
indicating that these social factors can act as confounding factors in analyses with cancer
and non-cancer diseases as endpoints. On the other hand, in other occupational populations,lower educational backgrounds are associated with more fieldwork and higher exposure
doses in lower-income groups. However, in this study population, the group with the highest
exposure dose (>100 mSv) has a higher proportion of TEPCO employees who have higher
educational backgrounds and higher annual incomes. This opposite association compared togeneral radiation workers suggests the need to consider whether an individual is a TEPCO
employee and the possibility of interaction between individual influencing factors when
conducting disease endpoint analyses. In epidemiological analyses with cardiovascular−63−

diseases as endpoints, besides strong risk factors associated with pathophysiology (such as
smoking and heavy drinking), psychological stress is also known as a risk factor. Additionally,
the effect related to disease onset is not necessarily linear, as moderate alcohol intake may
even have a protective effect. It is recommended to evaluate whether the data collected until
the second phase are sufficient for the analysis.
There was a relationship between the evacuation experience and the exposure dose inthis study population. Although no in-depth analysis has been conducted on this aspect,
it is likely that it simply reflects the fact that many employees of TEPCO and affiliatedcompanies, who originally resided in the evacuation area and worked at the nuclear power
plant, were involved in high-exposure operations during emergencies and inevitably had toevacuate. On the other hand, the evacuation experience may be associated with the level ofsocial and psychological stress, as well as the living environment of the residence (urban vs.
rural). Psychosocial stress and living environment in the residential area have been identified
as confounding factors in previous epidemiological studies with cancer and non-cancer
diseases. Therefore, it is necessary to seek more appropriate parameters that are related toevacuation experience.
Health literacy as a social factor includes exercise habits, eating habits, and the rate ofregular health checkup. It seems necessary to confirm whether these factors are covered bythis study.
3) Dose evaluation
In radioepidemiology, organ dose is an important indicator for studying the effects ofradiation exposure. External exposure dose is estimated based on information from theindividual monitor, allowing relatively accurate information to be obtained. However, inthe estimation of internal exposure dose, indirect evaluation of organ dose is based on
the information from whole-body counter (WBC) and analysis of nuclide concentrationin the air. Therefore, it is necessary to evaluate the uncertainty of the estimated values
corresponding to the organ dose levels.
In the first phase, an experiment was conducted to assess whether the effective dose
specified by laws and regulations could be appropriately evaluated based on the indicatedvalue of the personal dosimeter. A RANDO phantom was used to examine the dependence
on the irradiation direction from the source, investigating both ROT (effective dose inrotating irradiation) and ISO (effective dose in isotropic irradiation). The results confirmed
the validity of using the indicated value of the personal dosimeter. In the future, it will benecessary to evaluate organ doses using information such as the dose conversion factor
of ICRP. Furthermore, it is expected to assess the accuracy of organ dose estimation in−64−

situations where the irradiation direction from the source and gamma-ray energy information
following an accident are uncertain.
In the second phase, a study was conducted to estimate the equivalent dose to the crystalline
lens from β-rays using the indicated value of the personal dosimeter. The β/γ dose ratio
was estimated through simulation, and an experiment was performed to assess the β-rayshielding effectiveness of a full-face mask. By calculating the correction factor to convert theindicated value of the personal dosimeter to the equivalent dose of β-rays for the crystalline
lens, it became possible to accurately estimate the β-ray dose to the crystalline lens, which
couldn't be directly measured by the personal dosimeter. However, when estimating thedose to the crystalline lens using this correction factor, it may be necessary to evaluate theuncertainty of the estimated dose (β-ray + γ-ray) for the crystalline lens, considering theuncertainty in the information used for the β/γ dose ratio.
In the evaluation of internal exposure dose, as a result of obtaining detailed information
beyond the effective dose through the MHLW, it becomes possible to estimate the dose
contribution of individual radionuclides from the simple estimation based on combined doseof iodine and cesium. This improvement is expected to enhance the accuracy of estimatingorgan doses resulting from internal exposure. Building upon measurements obtained from
WBC, a foundation has been established to estimate thyroid doses in workers in whom I-131
is not detected, using information such as the ratio of airborne concentrations of I-131 andCs-137. Additionally, an estimation method using the furnace inventory has been developed
to determine the contribution of short half-life radionuclides (such as I-132 and Te-132) tothyroid doses. While this method is effective for estimation of short half-life radionuclides,
it is important to consider that the time of intake significantly affects the nuclide ratio andthe chemical form greatly influences dose estimation. Therefore, evaluating the uncertaintyof the estimation is inevitable. It is expected that the uncertainty of the dose estimation fora given dose level should be evaluated. Furthermore, after the initiation of stable iodine
administration following the accident, the internal exposure to I-131 is suppressed. Thus,in the assessment of thyroid doses based on the I-131/Cs-137 ratio, it is essential to haveinformation regarding the administration of stable iodine and the timing of its intake.
The accuracy of estimation should be further improved according to the level of organ
doses, including thyroid dose, obtained through these estimation methods. Special attention
should be given to the accuracy of estimating thyroid doses in workers whose effective dose
exceeded 250 mSv.
Using the frequency of translocated chromosomes as an indicator, biological dose evaluation
proves to be useful for validating the physically estimated organ dose. An nalysis is being
conducted on 74 workers with an effective dose of ≥ 70 mSv. It is known that smoking−65−history and medical exposure history influence the biological dose estimation. Therefore, it is
not possible to estimate the radiation dose from emergency operations solely on the frequencyof translocation chromosomes. An assessment that takes into account the frequency ofaccumulated natural radiation associated with age, in addition to the number of CT scans
and smoking history (number of cigarettes, etc.), is necessary to improve the accuracy.
Gathering information (medical exposure and number of cigarettes) is essential for enhancing
accuracy. It is expected that the uncertainty of the dose estimation, considering insufficient
information and inter-individual variability, will be evaluated.
4) Investigation of cause of deathWith regard to the investigation of the cause of death in 19,812 emergency workers in the
nuclear power plant accident, it should be highly evaluated that the researchers were working
hard to obtain consent and made efforts as much as possible for the subjects who can befollowed up. Although only 3,646 (18.4%) of the study participants have given consent forthe cause of death investigation, it is important to note that the process of obtaining consent
was initiated midway through the study when it was initially deemed unnecessary. Given thecurrent status of consent acquisition and even considering the potential number of participants
who may provide consent in the future, analyzing the cause of death with such a sample size
appears to be extremely challenging.
Solutions to address this issue will be addressed in the recommendations for the third phase.
5) Cancer morbidity investigation
The question of whether there is an increased incidence of cancer among emergency workers
after the nuclear accident is a matter of significant public concern, highlighting the crucial
importance of accurately understanding cancer morbidity. Consent for the use of the cancer
registries has been obtained from 7,537 participants, and it is important to track cancer
incidence by continually cross-checking with the national cancer registry.
However, the number of participants who have provided consent in this study falls short ofhalf the total number of emergency workers. Consequently, the tracking of participants who
have not given consent poses a challenge, and recommendations are proposed to address
this issue.
Furthermore, cancer cases prior to 2015 will be supplemented by regional cancer registries.
Considering the latency period from radiation exposure to cancer onset, it is likely that the
number of cases during this period is relatively low. Nevertheless, for the sake of ensuring
data integrity, it is deemed valuable to investigate cancer incidence in all 47 prefectures,
even if conducted gradually, covering several prefectures at a time.

−66−6) Thyroid cancer investigation
The first research topic is to utilize the data of comprehensive examination of those who
were required to undergo the detailed examination in the " Study on Thyroid Survey andOthers in Workers of TEPCO Fukushima Daiichi Nuclear Power Plant " project, fundedby the MHLW in the 2013 fiscal year (Principal Investigator: Tomotaka Sobue, hereinafterreferred to as the previous research team). As reported in the 2020 report, data was obtained
from 627 individuals out of the total 2,064 participants who consented to their data being
used for the NEWS study. Among them, 531 individuals (274 in the exposure group and 257
in the control group) underwent thyroid ultrasound examinations during the baseline survey.
If there is a possibility of acquiring additional data from the previous research team, apartfrom the 627 individuals, it is recommended to continue efforts to obtain it.
The second research topic involves investigating the implementation method for conducting
thyroid ultrasound examinations on approximately 20,000 emergency workers as part of theNEWS study. This topic aims to integrate data from the previous research team, as well as
data from newly conducted thyroid ultrasound examinations in the NEWS study, including
consent for the examinations and data on examination accuracy control. The high rates ofconsent obtained for the thyroid examinations are commendable, with 4,633 individuals(77.1%) of 6,006 participants in the baseline survey, and 1,101 individuals (83.0%) out of
1,326 in the first follow-up survey agreeing to participate. Additionally, training sessions havebeen conducted for examiners to ensure accuracy control in thyroid ultrasonography, andcertified technicians have been trained. Furthermore, a thyroid ultrasonography information
system has been established, through which image data and findings are transmitted to Jichi
Medical University for central assessment by the Accuracy Control Committee. These
achievements have been highly evaluated as they have led to the establishment of a framework
for advancing thyroid ultrasonography while maintaining accuracy.
Both research topics are progressing smoothly. In the third phase, the following points andcontinue the investigation accordingly are expected.
Since the definition of the longitudinal study population has not been clearly stated, it isnecessary to include it in the report. The subcommittee report for the fiscal year 2019 stated,“According to the guidelines of the MHLW, individuals whose effective dose exceeds 100 mSv
during emergency operations should undergo thyroid tests once every 3 to 5 years.” However,
the actual longitudinal survey population consists mostly of individuals with an effective
dose below 100 mSv. Therefore, it is unclear how the longitudinal survey population wasdetermined.
The data analysis is progressing smoothly. There is a slight tendency for a higher incidence
rate of thyroid cancer in the population with an effective dose of 50 mSv or higher. On the−67−other hand, the prevalence rates of nodules, cysts, and hypothyroidism increase with age
at the time of examination, but no association was observed between the effective dose
and these conditions. The association between thyroid cancer and radiation dose is subject
to confounding factors and bias, necessitating further detailed analysis. There are biases
in the examination supply system, such as a higher rate of visits to collaborating medical
institutions that are unable to perform ultrasound examinations in the low-dose group.
Additionally, there is a trend of higher examination consent rates in the high-dose group.
In fact, the population with higher effective doses has undergone a greater number ofultrasound examinations.
Regarding the quality control of ultrasound examinations, central assessments of primary
examination images are being conducted. The central assessment rates for the participants
with a dose of > 50 mSv were 66.7-72.9% in the baseline survey, compared to 47.1-50.7% in
the participants with a dose of < 10 mSv. In the follow-up survey, the rates were 93.3-100%
and 79.3-85.7% respectively. It is necessary to examine whether there are any systematicdifferences between local assessments and central assessments through a sample survey.
Furthermore, accuracy control has not been implemented for image diagnosis and decisions
on needle biopsy in the secondary examination. Therefore, there is a concern that compliancewith the guidelines for active surveillance of micro cancers with a major axis length of lessthan 10 mm may vary between facilities that regularly observe a large number of thyroid
cancer cases and local facilities with a smaller number of cases. It is important to be cautious
about the regional variations in compliance with active surveillance guidelines, as they canbe a confounding factor in the detection rate.
In conclusion, the study is progressing smoothly. However, there are factors that could
introduce bias, and it is necessary to analyze their impact.
7) Cataract investigation
Cataract is characterized by the clouding of the crystalline lens, with aging being the primaryand most significant risk factor. However, radiation also has a noticeable impact. Cataract
can be effectively treated through surgery, allowing for the restoration of visual acuity. Thereis a tendency to perform surgery when cataracts are diagnosed at an early stage or withmild symptoms, which makes studying the onset mechanism and epidemiology challenging.
Therefore, investigating the influence of radiation is crucial as it may provide valuable
insights into the study of cataract onset mechanisms.
In this study, a significant number of screenings were conducted, examining in detailvacuoles and other changes detected through transillumination. There is a trend of earlycataract surgery in recent years. Simply studying clear changes in the crystalline lens, such as−68−cortical cataracts, is insufficient for monitoring the progression. By detecting vacuoles, which
represent early changes, using a transillumination camera, it was discovered that vacuoles
can be present and detected even in individuals aged 30-40, and that visual acuity is often
good despite the presence of vacuoles. These findings, obtained through the world's firstlarge-scale study, are highly valuable.
In previous studies, the Lens Opacities Classification System (LOCS) and similarclassification systems were used, which requireda high level of examiner subjectivity.
Therefore, the utilization of transillumination cameras, which excel in detecting earlycataract changes like the presence of vacuoles, along with the ophthalmologists' diligent
research into the causes when adequate transillumination cannot be attained, are highly
commendable. Nonetheless, detecting changes in vacuoles can be challenging with slit-lamp
microscopy, and if this method is only available procedure, there may be difficulties incomparing and reconciling the findings of both examinations.
According to a questionnaire survey conducted among TEPCO employees, it was foundthat there was a higher prevalence of cataracts among individuals exposed to high radiation
doses. However, it is important to consider that the accessibility for high-dose individuals
to seek medical examination might have influenced the results. Additionally, there is apossibility that participants misunderstood Stage 1, which includes vacuoles detected throughtransillumination, as cataracts and responded accordingly. Therefore, it is crucial to clearly
distinguish between the early changes in the crystalline lens and the definition of cataracts.
Human observation alone makes it challenging to standardize the results of thetransillumination camera and slit lamp examination, hence the desire for AI implementation.
Fortunately, the automatic detection of vacuoles has been successfully implemented. This
automated method has demonstrated impressive results, achieving a sensitivity of 90% andspecificity of 96%. These findings pave the way for standardization and deserve high praise.
8) Psychological impact investigation
Further analysis should be conducted to explore the dose as an exposure factor, and continuous
investigation and observation of psychosocial effects, including behavior, is necessary.
When conducting analyses, it is important to adjust for major confounders, including
age and educational background. Adequate consideration of confounding factors from aliterature perspective, such as identifying confounding factors within the general population,is crucial when adjusting for confounders in the analysis of each event.
For life events that serve as exacerbating factors of anxiety and mood disorders, it has
been reported that the following were frequently experienced within the past year: "Workrelated events (promotion, reassignment, and work-related conflicts)," " illness or injury,"−69−

"discrimination against TEPCO employees," "experience of evacuation," "family separation
or living apart," as well as other personal events (marriage, divorce, relocation, traffic
accidents, etc.) and family issues (illness, death, etc.). It is important to analyze which ofthese specific factors served as aggravating factors.
9) Health management database
The establishment of a health management database for emergency workers contributes toongoing Personal Health Record (PHR) and the maintenance and promotion of the healthof users. This idea is preferable. Long-term health surveys are expected to make significant
contributions to enhancing the health of aging study participants. It may also be used as avaluable means of follow-up of study participants. In addition, it is expected to become a tool
to improve the self-care of participants.
Effective feedback of information to encourage continuous participation in the study is
an important issue, and health interventions using health examination data have shown
numerous successes so far. Therefore, it is desirable to make further efforts to consolidate
knowledge of healthcare apps. Also, health intervention may modify the outcome toward
radiation effects. Therefore, it is necessary to provide detailed descriptions of how changes
in lifestyle and health status resulting from these interventions are assumed to be associatedwith modifications to radiation damage.

−70−

Chapter II

Suggestions for the Third Phase Study

1) Research management structure
The Research Center for Prevention from Radiation Hazards of Workers at the National
Institute of Occupational Safety and Health, which serves as the study headquarters, is
responsible for overseeing and directing this epidemiological study, which is planned tohave a follow-up of 5 years in the second phase and 30 years in the subsequent phases. The
materials provided for the Third-Party Committee indicate that there are four researchersaffiliated with this center, while the website mentions two researchers. However, all of them
are non-regular researchers without salary increases or bonuses. It can be inferred thatthe study has been sustained so far through individual efforts. Nevertheless, the current
composition of having only non-regular researchers in the organization is unusual andprecarious, and it is not stable or attractive for both the current researchers and young
researchers who may consider participating in the study in the future. If MHLW, which has
been directing and sponsoring the implementation of this epidemiological study, and theJapan Organization of Occupational Health and Safety, the contract organization, recognize
this study as academically significant for Japan both domestically and internationally, we
propose transforming the Research Center for Prevention from Radiation Hazards ofWorkers into a resilient organization capable of continuing the research for the next 30 years.
Furthermore, concerns have been raised by the subcommittee about the difficulties inensuring a study environment, stating that " we are not dedicated research institutions or
personnel." Therefore, a comprehensive examination is necessary regarding the organizational
structure for the implementation of the study in the third phase.
In the midst of these circumstances, there is a lack of clear division of roles between the
study headquarters and each subcommittee. Although it is stated that "the final selectionand examination of confounding factors in the assessment of major health effects, such asradiation exposure, will be conducted by the control of headquarters for the survey in thethird phase, the positioning of the study headquarters remains a challenge. It is unclear
whether the study headquarters can assume the role of the control headquarters, or if thestudy headquarters and each subcommittee should jointly establish and take charge of thecontrol headquarters.
2) Follow-up of the cohort and subcommittee and study organization
Unfortunately, the number of responses and the number of new participants in the postal
survey are not sufficient, and it is also not expected to see a substantial increase in the future.
While we are planning to continue recruiting new participants in the third phase, the more−71−

important and demanding focus should be on the tracking, retention, and dropout preventionof the current study participants, numbering over 6,000. Even if the participation rate is onlyaround 30%, a high follow-up rate will greatly enhance the reliability of the study data. To
improve the follow-up rate and gain a proper understanding of the cohort’s characteristics,
it is necessary to understand the socioeconomic characteristics of not only the current study
participants but also all emergency workers. Emergency workers belong to thousands ofcompanies, and so, they should have diverse socioeconomic backgrounds. Additionally,various health support programs, such as cancer screenings, provided by the government andworkplaces, overlap and compete depending on radiation exposure levels and other conditions.
Furthermore, with participants retiring in the future, the responsibility for conducting
health examinations is transitioning from workplaces to local communities. In this context,
the "Expert Review Committee on the Vision of the Epidemiological Study of Emergency
Workers at TEPCO Fukushima Daiichi Nuclear Power Plant", which was responsible forpreparing start of this research project, has determined that cancer screenings should be
included in the health examinations. However, it is currently not feasible due to budget
constraints. It is necessary to evaluate the significance of conducting cancer screening every
5 years. Moreover, the incidence of cancer, particularly in the thyroid and prostate glands,
has significantly increased, warranting examination of potential overdiagnosis. To ensure thelong-term continuity of the cohort, it is advisable to consider integrating various initiatives
at this opportunity.
The MHLW has its own database, which the NEWS study utilizes, while relevant companies
have their own records. Handling them separately in each organization is inefficient. It isdeemed essential to aggregate or cross-reference the data in the NEWS study.
Amid limited human and financial resources, it is important to allocate resources tonecessary studies and prioritize them, while also streamlining low-priority studies. For
example, the following items can be considered.
Clinical Investigation Subcommittee (I): The study that resembles the Life Span Study(LSS) cohort of A-bomb survivors is intriguing, but surpassing the LSS, except for thedifferent radiation exposure scenario, is deemed difficult. It is anticipated that the study may
not surpass NIPPON DATA and other studies in terms of population representativenessand the number of participants. We kindly request a reassessment of the significance ofcontinuing this survey in the planning of research plan for the next 5-year term.
Clinical Investigation Subcommittee (II): The primary significance is believed to lie in theidentification and assessment of necessary confounding factors. However, has this objective
remained unachieved in the first and second phases?
Storage of biological samples: Blood and urine samples are stored for future research, and−72−

blood samples are specifically stored for human genome/gene analysis. We would appreciate
a consideration of the possibility to narrow down the participants and samples for blood andurine storage by clearly defining the research objectives in the thrid phase.
Taking these points into account, we kindly request the research team to thoroughly
deliberate and design the implementation framework for the third phase, including thedecision on potential discontinuation.
Data on confounding factors have been collected in the questionnaires in the first andsecond phases, and it is expected that the amount of information neccesary in the third
phase will be relatively small. It is important for the central headquarters to discuss the future
direction of these subcommittees. In the future, it is crucial to have the participation ofresearchers with high expertise in epidemiology and statistics, exceeding the current level ofexpertise within the team. Therefore, the supply of highly specialized researchers, particularly
for the "Clinical Investigation Subcommittee (II)", is considered necessary.
Would it be worth considering the promotion of utilizing Rosai Hospital, an institution
within the same organization, as the designated facility for conducting the headquarterssponsored centralized health examinations? For instance, we could explore the possibility of
establishing a specialized Research Center for Health and Employment Support, which could
serve as a central point of contact. This center could be set up in multiple Rosai Hospitals,
known for their proactive approach in connecting patients with society.
One of the challenges that long-term cohort studies face is the potential disruption of
temporal continuity of results due to the improved performance of diagnostic instruments
and laboratory measurement techniques. Variations resulting from the improvement ofdevice performance, which may not pose a significant problem in actual clinical practice, canhave a substantial impact on this epidemiological study that focuses on subclinical effects.
Therefore, it is a challenging issue to address. How about considering implementation of asystem to continuously monitor this problem?
As stated in the report of the Analysis and Evaluation Subcommittee (Shinji Yoshinaga), it
has been reported that the original population size of this cohort is not sufficiently powered
to examine the risk of cancer. Therefore, in such circumstances, it is necessary and feasible
to consider methods for controlling confounding factors through continuous analysis within
the future research framework. This includes measures such as the standardization ofradiation dose surveys, standardization of health check-up data, and prevention of increasein the rate of follow-up loss among the participants. To achieve this, it is crucial to establish
an organization capable of maintaining a long-term research system and to establish afoundation for the continuity of the study.
It is requested that the study headquarters and the subcommittees engage in discussions−73−

and make a determination regarding the adequacy of obtaining sufficient information onsocial factors from the research results in the first and second phases. Additionally, theyshould consider whether it is necessary to obtain further information on potential new
confounding factors in the future.
Social factors addressed within the Clinical Investigation Subcommittee (II) hold significant
importance as information on confounding factors for analyzing health effects, including
cancer. However, it is requested that the design of the third phase be determined after
careful examination within the research team to ascertain the possibility of discovering
additional important information beyond what has been revealed in the first and second
phases. Furthermore, attention should be given to ensuring a conducive research environment
for this subcommittee.
In the analysis conducted by this subcommittee, the confounding effect of alcohol
consumption on systolic blood pressure was not examined in the context of the relationshipbetween educational background and blood results. Similarly, the confounding effect ofsmoking was not considered in relation to white blood cell count. It is speculated that theresults would have been different from what was reported if the amount of alcohol intake
and the amount of smoking were also adjusted using analysis of covariance. This aspect may
be due to the absence of dedicated research institutions and researchers, as mentioned by
the investigator themselves.
It is essential to thoroughly examine whether it is possible to select appropriate confounding
factors in the final evaluation of major health effects, such as radiation exposure.
The issues are listed as individual suggestions.
①Further investigation is needed to explore methods for controlling confounding
factors and correcting bias in the identification of non-cancer diseases. Additionally,
it is anticipated that there are differences in the opportunities and quality of healthexaminations between TEPCO workers and other workers. Therefore, it is importantto analyze the factors that may impact the occurrence and prevalence of non-cancer
diseases attributed to the differences between TEPCO workers and non-TEPCO
workers. We look forward to future surveys and analyses that leverage the extensive
experience of RERF.

②

The postal survey (pilot survey) indicates that there is a potential increase in thenumber of participants willing to cooperate with this study after retirement, suggesting
the importance of continuing the postal survey in the thrid phase.

③

The assessment of whether there is a risk of cardiovascular disease in the dose range
below 500 mSv, particularly below 100 mSv, is a significant challenge in the fieldof radiation protection. Due to limited statistical power, significant results cannot−74−be expected in epidemiological surveys that rely on stochastic effects as endpoints.
However, it would be an intriguing analysis if early changes in arteriosclerosis, suchas calcification of the aortic arch and abdominal aorta, as well as variations in carotid
intima media thickness (IMT), can be quantitatively evaluated. Therefore, it is
crucial to prioritize the development of tools for the quantitative evaluation of XP and
ultrasound image data for the third phase.
④

It is anticipated that in the future, a pooled analysis can be conducted between thisstudy, which utilizes the dose of emergency radiation exposure after the Fukushima
Nuclear Power Plant accident, and the epidemiological study of radiation workers
conducted by the Radiation Effects Association using the radiation dose during
planned radiation exposure. To ensure a smooth pooled analysis, it is important toconfirm that there are no discrepancies in the questionnaire regarding confounding
factors between both surveys. This aspect should also be verified in the third phase.

3) Statistical power and analytical methods
The statistical power calculation has indicated the difficulty in verifying the currently
estimated risk values from epidemiological studies of A-bomb survivors. However, it isnecessary to examine the power calculation specifically for thyroid cancer. In studies ofA-bomb survivors, the risk of thyroid cancer from adult exposure is scarcely detected inanalyses that exclude patients with micro-cancer (Furukawa et al. Int. J. Cancer: 132, 12221226 [2013]). On the other hand, a significant correlation with dose has been reported inanalyses focusing on the endpoint of latent thyroid cancer and nodules (Ezaki et al. https://doi.org/10.1269/jrr.32. SUPPLEMENT_193). Since ultrasonography can detect microcancers, it has the potential to detect the presence or absence of a radiation effect on thyroid
cancer that has not been included as an analysis target, either as micro-cancer or latent
cancer. Therefore, a reconsideration of the power calculation is necessary.
This study should aim to investigate not only the current risk estimates but also theunderlying reasons for the difficulty in estimating risks. By quantitatively elucidating
confounding factors such as lifestyle habits, it has the potential to contribute to understanding
the reality of radiation risks. Among the confounding factors, it is necessary to quantitatively
evaluate and analyze smoking and drinking. In terms of analysis evaluation, considering
the limitations and characteristics of NEWS study, it is important to acquire data necessary
for investigating the occurrence of radiation effects and to conduct appropriate statisticalanalysis that includes confounding factors. This will ensure that the study estimates themagnitude of radiation risks.

−75−4) Dose evaluation
The accuracy of dose estimation has been improved through research that addresses therespective dose evaluation challenges of external and internal exposure. However, due
to limitations in physically measuring emergency workers' exposure, the biological dose
evaluation through chromosomal aberration frequency measurement becomes crucial
complementary data. History of medical exposure should be taken into consideration
when analyzing chromosomal aberration. Additionally, medical exposure history serves asimportant information for biological dose surveys. In order to further advance the biologicaldose evaluation using chromosomal aberration frequency, it is recommended to also examine
the estimation of medical exposure history. Some emergency workers were advised to takestable iodine preparations to avoid excessive intake of radioactive iodine. Since this factor
affects the evaluation of thyroid dose, it should be taken into account when evaluating
the intake of radioactive iodine through estimation, rather than relying solely on direct
measurement.
5) Investigation of cause of death
This study is highly significant in investigating the radiation hazards in an unprecedented
nuclear power plant accident that will be remembered in human history. It has garneredsignificant attention worldwide, and as a research endeavor, it is essential to analyze the entire
dataset regarding deaths and causes of death as expected hard outcomes. Epidemiologicalstudies require long-term follow-up, and ethical guidelines for research have evolved overtime, with the possibility of future changes in the future. It would be a loss for humanity
if the understanding of radiation hazards is compromised by biased data resulting from
unpredictable guideline changes, especially considering the substantial research funding
drawn from taxpayers. Obtaining informed consent is not possible due to the occurrenceof fatalities. Currently, there is a focus on returning the study's findings to the public.
Therefore, to establish a review committee that includes perspectives from scientific ethics,
legal experts involved in research, and the general public. This committee would reconsider
matters regarding the consent of study participants, exploring possibilities such as whether it
is unnecessary or opt-out options are viable.
6) Cancer morbidity investigation
To track cancer incidence, data up to 2015 were collected and matched with the regional
cancer registry, while data from 2016 onwards were matched with the national cancer registry.
The regional cancer registry is responsible for managing cancer incidence up until 2015 in
all 47 prefectures, and as of 2023, it is believed that the data is largely complete. Conducting−76−

the investigation once is deemed sufficient, and there is no need for future implementations.
It is considered feasible to gradually carry out the investigation.
The low rate of obtaining consent has been a bottleneck for the national cancer registry.
However, there is a possibility that consent is not set as a mandatory condition in Article 17of the Act on Promotion of Cancer Registry. This article stipulates the provision of national
cancer registry information by the MHLW for "research studies on cancer necessary forplanning or implementing national cancer control measures."
While it is essential to avoid the misuse of consent exemption for ethical reasons, it is worth
considering the applicability of consent exemption under the mentioned article in consultation
with the responsible section in the MHLW. This consideration takes into account the social
importance of the study and the fact that it represents the sole opportunity to learn from the
Fukushima Nuclear Power Plant accident, acknowledging its irreplaceable nature.
7) Thyroid cancer investigation
The report indicating a significantly higher standardized incidence ratio (SIR) of thyroid
cancer can be understood in light of existing findings. If the morbidity used to calculate
the expected value is based on the clinical incidence of thyroid cancer, the expected value
will be calculated to be smaller. As mentioned in the report's comment, over-detection
by screening may inflate the observed value, resulting in an overestimation of the SIR. In
order for the SIR to be scientifically valid, expected values should be calculated based on the
thyroid cancer morbidity, including early-stage thyroid cancer that does not exhibit clinicalsymptoms in the general population undergoing screening. However, the International
Agency for Research on Cancer (IARC) recommends against thyroid screening for thegeneral population following a nuclear accident*. In other words, it is not advisable torecruit non-exposed individuals who have not participated in disaster prevention activities
and conduct thyroid cancer screening anew. Therefore, if information on the thyroid
cancer morbidity in the general population is found through existing thyroid screening, it
is recommended to recalculate the SIR using that information. If no existing information isavailable, the change in morbidity according to radiation dose will be examined within the
study population recruited until the second phase, considering a low-dose exposure group(criteria for group classification are subject to discussion) as a control group. However, it isimportant to appropriately adjust the confounding factors (candidates) in the final model.
This includes factors such as the screening rate and frequency of examinations by the same
individual, differences in image assessment accuracy between central and local assessments,
and whether there are any dose-related differences in adherence to guidelines from academic
societies recommending active surveillance instead of immediate surgery for micro-cancers,−77−as pointed out in Chapter I, as these factors can influence the detection rate.
* I ARC TECHNICAL PUBLICATIO NO.46, THYROID HEALTH MONITORING
AFTER NUCLEAR ACCIDENTS, 2018.
8) Cataract investigation
In the last year of the second phase, it is desirable to verify the comparison and consistencyof findings between transillumination and slit lamp examinations for Vacuoles, which represent
the early stage of posterior subcapsular opacity, as they are prone to bias caused by medical
examination.
In the third phase, the following aspects are expected. Firstly, in analyzing the relationshipbetween radiation dose and cataracts, it is important to clarify the definitions of "cataract"and "changes in the crystalline lens." It may be preferable to use terms such as "Stage 1" or"Stage 2 and above" instead of "changes in the crystalline lens" or "cataract" to minimize
subjectivity. Secondly, as cataract surgeries are often performed at an early stage nowadays,
it is necessary to clearly define the endpoints when evaluating the long-term effects ofradiation. Considering that the radiation effects in this case might be very small and may not
be classified as cataract but rather as Stage 1, it is recommended to perform analyses withendpoints placed solely in Stage 1, as well as analyses considering cataracts including Stage
2 and above. However, it should be noted that TEPCO employees, who undergo frequent
screenings, may have a higher detection rate for cataracts and changes in the crystalline
lens. While aging is the primary risk factor for cataract development, it is advisable toconsider other risk factors besides age. If radiation dose is a concern, it is necessary to take
into account occupational radiation exposure in addition to medical radiation exposure.
Lastly, it is acknowledged that there is a potential for bias in evaluations based on humanobservations, and therefore, further utilization of AI is encouraged.
9) Psychological impact investigation
As we continue with the further analysis using radiation dose as an exposure factor, it is
crucial to conduct ongoing and detailed investigations of the psychological and social impacts,
including behavior.
In the follow-up survey, the events such as retirement, unemployment, and the presenceof isolation or loneliness are planned to be measured. It is important to always verify thechronological sequence of these events and, during the evaluation, carefully examine theinterrelationships among the factors and be cautious about the possibility of reverse causality.
Therefore, in order to achieve the initial objective of elucidating the mid- and long-term
mental health of emergency workers, it is recommended to continue conducting thorough−78−

follow-up surveys and analyses. It is speculated that the influence of events occurring duringfollow-up on the association between exposure factors and outcomes is not straightforward,
thus necessitating investigation and analysis to clearly understand the interrelationships
among the factors.
10) Health management database
If behavior change is expected to observe through the use of a database, it will be insufficientto have information merely on the deviation of health examination data from reference values.
It is important to incorporate thoughtful measures, such as utilizing algorithms derived fromreliable sources like NIPPON Data, to provide evidence-based risk assessments.
Considering the purpose of constructing a database for the lifelong and comprehensive
monitoring of overall health status, it is necessary to conduct ongoing discussions andconsiderations for sustainable business continuity, including financial support.

−79−

Chapter Ⅲ

Evaluation of the Second Phase Study and Suggestions for the Third Phase
Study [Summary]

The NEWS is conducted utilizing information provided from the government-created andmaintained database in collaboration with TEPCO, while also inviting participants. As aresult, the cumulative number of study participants reached 8,023 over a period of 6 years
since the study began, and the cumulative number of workers who received health examinations
reached 6,286, highlighting the importance of recognizing the participants' understanding
and the efforts made by the researchers.
The characteristics were observed in attributes such as affiliated company, age, educational
background, and marriage rate as well as in the prevalence of hypertension, diabetes, andcardiovascular diseases when observed by exposure dose group in the baseline survey. It was
indicated that potential confounding factors should be identified among these characteristics,
and after understanding methods to control for confounding, the causal relationship between
exposure dose and disease onset should be investigated.
The calculation of statistical power in the second phase demonstrated that, over a 40 years
of follow-up, the maximum statistical power for detecting any type of cancer was approximately
10%. However, it is crucial to elucidate the survey methodology for patients with non-cancer
diseases and the measurement techniques used. This investigation should aim to determine
which indicators can be used to control confounding in the analysis of the relationship between
radiation exposure dose and non-cancerous diseases, as well as whether bias can be corrected.
Despite the low statistical power, the significance lies in the ability to disseminate evidencebased information from the perspective of worker health management, emphasizing thatlifestyle improvements, rather than radiation risks, contribute to risk reduction, considering
the high quality of dose measurement and thorough investigation of confounding factors.
In the second phase, significant associations were observed between educational
background and variables such as systolic blood pressure, white blood cell count, HbA1c, and
γGTP. Even after adjusting for age, an inverse association was observed between educational
background and smoking as well as drinking habit. Additionally, a similar inverse association
was found between annual income and smoking. These results support the general hypothesisthat higher education is associated with higher health literacy, indicating that these social
factors can be confounders in epidemiological studies focusing on cancer and non-cancer
diseases as endpoints.
In the second phase, the crystalline lens equivalent dose from β-rays was estimated basedon the indicated value of the personal dosimeter. The ϐ/γ dose ratio was estimated throughsimulation, and an experiment was conducted to assess the β-ray shielding performance−80−using a full-face mask. As a result of this experiment, a correction factor was calculated
to convert the indicated value of the personal dosimeter to the crystalline lens equivalentdose from β-rays, enabling the accurate estimation of β-ray doses to the crystalline lensthat could not be directly measured by the dosimeter. Regarding the evaluation of internal
exposure dose, it became possible to estimate the dose contribution of each nuclide byutilizing the effective dose as the combined dose of iodine and cesium. This improvement
enhances the accuracy of estimating organ doses resulting from internal exposure. Using
information obtained from WBC, a foundation was established for estimating thyroid doses
in workers where I-131 was not detected. This estimation was based on factors such as theratio of air concentrations between I-131 and Cs-137. Additionally, an estimation method
was developed using the inventory ratio inside the reactor to determine the contribution
from short half-life nuclides (e.g., I-132 and Te-132) to thyroid dose. This method proveseffective for estimating doses from short half-life nuclides.
The biological dose evaluation, using the frequency of translocated chromosomes as anindex, serves as a validation of the accuracy of physically estimated organ doses. Currently,
an analysis is being conducted on 74 workers with an effective dose ≥70 mSv.
It is commendable that researchers have made diligent efforts to obtain consent andhave made considerable efforts to follow up with the participants who can be traced in theinvestigation of the cause of death. However, even considering the number of participants
expected to provide consent in the future, analyzing the cause of death may still be challenging
due to the limited sample size.
The question of whether the cancer incidence increases in radiation workers after
the nuclear accident is a matter of significant social concern. Thus, needless to say, it isvery important to grasp the accurate cancer morbidity. Consent for the use of the cancer
registry has been obtained from 7,537 workers, and it is crucial to track cancer incidence bycontinuously cross-referencing with the national cancer registry. However, since consent
has been obtained from less than half of all emergency workers, tracking individuals without
consent remains a challenge.
In the thyroid cancer investigation, the first research topic focuses on utilizing the datafrom the previous research project led by Prof Tomotaka Sobue(as mentioned earlier).
As reported in the 2020 report, data from 627 individuals who consented to the use of
their data for the NEWS study were obtained out of the total 2,064 participants. If there
is a possibility of acquiring additional data from the previous research team beyond the627 individuals, continued efforts should be made to obtain it. The second research topic
involves the integration and collection of data from the previous research project, as wellas the newly conducted thyroid ultrasound examinations in the NEWS study, consent for−81−these examinations, and accuracy control of the examinations. An information system forthyroid ultrasound examinations was established, whereby image data and findings were sent
to Jichi Medical University for central assessment by the accuracy control committee. Thissystem allows for the implementation of thyroid ultrasound examinations while maintaining
accuracy, and it is highly regarded as an achievement.
In the cataract investigation, a considerable number of individuals underwent thoroughexaminations, specifically analyzing vacuoles and others detected through the transillumination
method. This detailed examination allows for accurate assessment. Notably, there is a
growing trend of early cataract surgery, and the detection of vacuoles, an early change,
through transillumination cameras has been observed. The results have revealed that vacuoles
can be detected even in individuals aged 30-40 years, and the presence of vacuoles does notnecessarily indicate poor visual acuity. These findings, obtained through the world's firstlarge-scale study, hold significant value. Therefore, this can be evaluated with the results of
the world’s first large-scale study. The use of the conventional LOCS and similar classification
systems for comparing and ensuring the consistency of examination findings has been achallenge. It is necessary to clearly distinguish between early changes in the crystalline lensand the definition of cataract.
In the psychological impact investigation, it is important to conduct further analysis using
radiation dose as an exposure factor, while adjusting for major confounding factors, including
age and educational background. It is crucial to thoroughly examine the confounding factors
from a literature perspective, considering "What factors may act as confounders in the general
population?" when adjusting for confounders during the analysis of each event.
The idea of establishing a health management database for emergency workers andconducting lifelong comprehensive health surveys (Personal Health Record or PHR), as wellas contributing to the maintenance and improvement of users' health throughout their lives
through its utilization, is considered favorable. Long-term health surveys are expected toplay a significant role in enhancing the health of study participants as they age. It may also
be used as a useful means of follow-up for participants. Moreover, there is an expectationthat it will serve as a tool to enhance the self-care of the participants.
Suggestions for the Third Phase Study
Research Center for Prevention from Radiation Hazards of Workers at the National Instituteof Occupational Safety and Health, serving as the study headquarters, oversees and directs
this epidemiological study, which is planned to have a follow-up period of 5 years in thesecond phase and 30 years in subsequent phases. As all researchers are non-regular staff
and the organization tasked with continuing the survey for the next 30 years is deemed−82−vulnerable, it is suggested that the MHLW, which provides guidance and sponsorship forthis epidemiological study, and the Japan Organization of Occupational Health and Safety,
the contracted agency, transform this center into a resilient organization capable of enduring
the 30-year follow-up period. Furthermore, since the subcommittees are not exclusively
dedicated to this study, securing a conducive research environment becomes challenging,necessitating substantial improvement in the implementation structure for the third phase.
The most important and demanding aspect is the tracking, retention, and preventionof dropouts among the current cohort of over 6,000 participants. In order to improve thefollow-up rate and gain a proper understanding of the cohort's characteristics, it is necessary
to comprehend the socioeconomic backgrounds of not only the study participants but also all
emergency workers. Emergency workers belong to numerous companies, numbering in thethousands, and exhibit diverse socioeconomic profiles. In addition, various support programs
offered by the government and workplaces, such as health examinations, are overlapping andcompeting with each other depending on factors such as radiation exposure dose.
Amid limited human and financial resources, it is important to allocate resources tonecessary studies and sort out low-priority studies through streamlining by integrating
projects.
The main issues are listed as individual suggestions.
①Further examination is needed to explore ways to control confounding factors andcorrect bias in non-cancer disease identification.

②

It is desirable to continue the postal survey in the third phase due to the retirement ofparticipants.

③

It is considered important to develop tools for the quantitative evaluation of image
data from XP and ultrasonography for the third phase.

④In order to conduct a pooled analysis between this study and the epidemiologicalstudy of radiation workers conducted by the Radiation Effects Association, it isimportant to ensure consistency in the questionnaire on confounding factors between
both studies.

⑤Quantitative evaluation and analysis of confounding factors such as lifestyle habits
including smoking and drinking are necessary.

⑥T he evaluation of biological dose by measuring the frequency of chromosomal
aberration is important as complementary data for dose assessment.

⑦

I t is recommended to establish a review committee to discuss the feasibility ofinvestigating the causes of death among all emergency workers.

⑧

It is worth considering the applicability of consent exemption for cancer incidence−83−survey.
⑨

In the thyroid cancer survey, confounding factors (candidates) should be appropriately
adjusted in the final model.

⑩

It is desirable to compare the findings of vacuoles, which indicate the early stage ofcataracts, using transillumination and slit-lamp microscopy.

⑪

In the psychological impact survey, it is necessary to continue conducting ongoingobservations and investigations into psychosocial effects, including behavior, whilefurther analyzing the dose as an exposure factor.

⑫

Efforts should be made in the health management database to provide evidence-basedrisk assessment, and it is necessary to consider various aspects, including financial
support, for the establishment of a lifelong database.

−84−

Attachment
Research management structure
Toshiteru
Okubo

Principal
Investigator
Headquarters

Research Center for Prevention from Radiation Hazardsof Workers, National Institute of Occupational Safety and
Health, Japan

TetsuyaMizoueHeadquarters

Research Center for Prevention from Radiation Hazardsof Workers, National Institute of Occupational Safety and
Health, Japan

Kenta
Tomonaga

Headquarters

Research Center for Prevention from Radiation Hazardsof Workers, National Institute of Occupational Safety and
Health, Japan

Huan Hu

Headquarters

Research Center for Prevention from Radiation Hazardsof Workers, National Institute of Occupational Safety and
Health, Japan

Shinji
Yoshinaga

Analysis and
Evaluation

Department of Environmetrics and Biometrics, Divisionof Radiation Basic Science, Research Institute for
Radiation Biology and Medicine, Hiroshima University

MakotoAkashi

Dose evaluation

Higashigaoka-Tachikawa Faculty of Nursing, Tokyo
Healthcare University

Osamu
Kurihara

Dose evaluation

Department of Radiation Measurement and Dose
Assessment, National Institutes for Quantum Science andTechnology

YumikoSuto

Dose evaluation

Department of Radiation Measurement and Dose
Assessment, National Institutes for Quantum Science andTechnology

Norio
Tsujimura

Dose evaluation

Radiation Protection Department, Nuclear Fuel Cycle
Engineering Laboratories, Japan Atomic Energy Agency

Takumaro
Momose

Dose evaluation

Fukushima Research & Development Base, Fukushima
Research & Development Division, Japan Atomic Energy
AgencyWaka
Ohishi

ClinicalInvestigation (I)Department of Hiroshima Clinical Studies, Radiation
Effects Research Foundation

HirokoKitamura

ClinicalInvestigation (I)Occupational Health Training Center, University ofOccupational and Environmental Health−85−

Hokuto
Hoshi

ClinicalInvestigation (II)The Hoshi General Hospital

KotaroOzasa

Cause of death/cancer morbidity

Health Management Center, Kyoto Prefectural Universityof Medicine

Tomotaka
Sobue

Thyroid cancer
surveyDivision of Environmental Medicine and Population
Sciences, Department of Social and Environmental
Medicine, Osaka University Graduate School of Medicine

Nobuyuki
Taniguchi

Thyroid cancer
surveyDepartment of Clinical Laboratory Medicine, Jichi
Medical University School of Medicine

Megumi
Miyagawa

Thyroid cancer
surveyDepartment of Internal Medicine, Miyagawa Hospital;
Department of Endocrinology and Metabolism,
Toranomon Hospital

Hiroshi
SasakiCataract survey

Division of Vision Research for Environmental Health,
Project Research Center, Medical Research Institute;
Department of Ophthalmology, Kanazawa Medical
University,

HisashiEguchi

Psychologicalimpact survey

Occupational Mental Health, Group of Occupational
Health Support, Institute of Industrial Ecological Sciences,
University of Occupational and Environmental Health

KosukeMafunePsychologicalimpact survey

Occupational Mental Health, Group of Occupational
Health Support, Institute of Industrial Ecological Sciences,
University of Occupational and Environmental Health

Akira
Ogami

Healthmanagement
database

Department of Work Systems and Health, Group of Social
Environment, Institute of Industrial Ecological Sciences,
University of Occupational and Environmental Health−86−

Headquarters and Sub-Investigation Committee Reports
1. Epidemiological Survey HeadquartersPrincipal Investigator: Toshiteru Okubo

In the operations for responding to the accident at TEPCO Fukushima Daiichi Nuclear
Power Plant, the emergency radiation exposure dose limit for emergency workers wasincreased from 100 mSv to 250 mSv from March 14 to December 16 in 2011. It is estimatedthat 19,812 workers were engaged in the operations during this period and 174 workers were
exposed to more than 100 mSv, which is the 5-year dose limit for normal work. The dose in
the rest of the workers was less than 100 mSv, and the total dose was less than 10 mSv in the
majority. The purpose of this study is to follow up the health effects of emergency operations
in all of these emergency workers throughout their lifetime.
We have been asking the target subjects of 19,812 workers to participate in the study
since the start of this study in 2014. The results until December 31, 2022 were as follows:
8,023 (40.5%) agreed to participate in the study; 3,843 (19.4%) refused participation; 4,992(25.2%) did not respond; 1,734 (8.8%) with unknown addresses; 757 (3.8%) died; and463 (2.3%) for others. Of the participants, 1,345 answered that they would only cooperatewith the study such as questionnaires but not undergo health examinations provided by
the study. Of those who wished to undergo health examinations, 6,286 (31.7%) underwent
health examinations planned by the study group. A total of 419 workers wished to undergo
health examinations but did not because of personal reasons or lack of nearby cooperating
institutions.
The places of residence of study participants are distributed nationwide, and there is noother way than establishing study cooperating institutions in each prefecture to promote
the health survey of all subjects. Thus, we asked at least one medical institution that mainly
conducts health examinations for workers in each prefecture to cooperate in the study andasked healthcare professionals who were in charge of health examinations such as publichealth nurses of the contract institutions to become study collaborators. The number ofcooperating institutions has been decreasing and there are currently about 60 institutions.
At the time of health examinations at each medical institution, blood and urine samples
are collected and laboratory tests are performed. There were considerable differences in thetest accuracy between institutions at the start of the study. Therefore, all samples collectedin various places in Japan were sent to a laboratory in Tsukuba City, Ibaraki Prefecture forcentralized analysis. In addition, a portion of blood and urine was dispensed for storage
and frozen at -80℃ so that past biochemical changes can be investigated if any healthabnormality is observed in emergency workers in the future.

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A health examination with multiple items which is performed at the first time ofparticipation in the study is called a "baseline health examination," and the second andsubsequent examinations are called "Lx health examination." The above number of thoseundergone the baseline health examination does not include L1 health examinations.
To date, the numbers of subjects who have undergone the L1 health examination (the first
follow-up examination after the baseline examination) by fiscal year were, 7 in 2019, 1,130 in
2020, 1,014 in 2021, and 1,116 in 2022 (including subjects to undergo health examinations),
with a total of 3,267. Since the baseline health examination was conducted over a long periodof 5 years, it is expected that some more workers will undergo the health examination in the
future. However, it may be necessary to consider making another effort to encourage themto continue the examination. In FY 2022, those who wished to have a health examination
since the beginning of the study in 2014 but were waiting for it accounted for only 5.2% of
all workers who wished to participate in the study.
As for the relationship between the exposure dose and age at the time of emergency
operations, the mean age in the group with exposure dose of < 5 mSv was the highest at
53.4 years (SD11.0). The mean age was the lowest at 49.6 years (SD10.7) in the ≥ 100 mSv
group. The marriage rate was the highest at 88.7% in the ≥ 100 mSv group and the lowest
at 78.8% in the 10 - < 20 mSv group. As for the educational background, the percentage ofuniversity graduates or higher was the highest at 41.0% in the < 5 mSv group and the lowest
at 21.7% in the ≥ 100 mSv group. The percentage of high school graduates was the lowest
at 39.8% in the < 5 mSv group and the highest at 70.8% in the ≥ 100 mSv group. When
comparing the percentage of people assigned to control the nuclear reactor by exposure
dose, the percentage was the highest at 56.6% in the ≥ 100 mSv group, followed by 43.7% in
the 50 - < 100 mSv group, and the lowest at 13.5% in the < 5 mSv group.
During the 10-month emergency operation period when the exposure limit was increased,
the percentage of those who worked for ≥ 7 months was the highest at 69.2% in the 50 - <100 mSv group, followed by 68.9% in the ≥ 100 mSv group. On the other hand, the < 5 mSv
group showed a relatively low percentage of 6.9%. In the < 5 mSv group, the percentage of
those who worked for 1 - 3 months was the highest at 75.2%.
In this study, "multi-item health examinations" equivalent to comprehensive medical
examinations are conducted once every 5 years and "basic health examinations" equivalent
to statutory regular health examinations are conducted every year for the participants. The
first round of the multi-item health examination is called the baseline health examinationconsidering the start of this cohort study. After explaining the purpose of the study to thefirst examinees, we asked them to give consent to the use of the health examination results
and to give their own hand-written signatures of their agreement. Then, we asked them to−88−complete a detailed questionnaire about their previous health history.
Among the questions related to past illness, the subjects with thyroid diseases and cataract
tended to be significantly more in the high-dose group. The percentages of hypertension
and dyslipidemia tended to be higher in the groups with higher exposure dose, but norelationship with the exposure dose was observed in the subjects with a history of cancer or
cardiovascular disease.
Next, the relationships of the health examination results to the contents of operations andthe exposure dose are described. We examined the relationships of the exposure dose andthe contents of operations in the baseline examinees with (1) peripheral blood test values,(2) parameters related to the so-called metabolic syndrome such as liver function tests,
glucose metabolism, lipid metabolism, blood pressure, and obesity, (3) renal function
parameters, and (4) C-reactive protein, prostate-specific antigen, and pepsinogen I/II ratio.
As a result, statistically significant differences between groups by exposure dose wereobserved in hematocrit, neutrophils, eosinophils, platelet count, alkaline phosphatase,leucine aminopeptidase, gamma-GTP, systolic blood pressure, abdominal circumference,
calcium, and inorganic phosphorus. Also, statistically significant differences between groups
by operation were observed in hemoglobin, hematocrit, mean corpuscular hemoglobin
concentration, white blood cells, total bilirubin, lactate dehydrogenase, alkaline phosphatase,leucine aminopeptidase, gamma-GTP, total cholesterol, HDL cholesterol, triglyceride,systolic blood pressure, abdominal circumference, creatinine, uric acid, chloride, calcium,and pepsinogen I/II ratio. However, all these statistical differences were incidental and were
not considered significant when observed by dose or operation.
The above report is the result of investigating the diagnosis results only once, and it cannot
deny that the result may be different if the long-term observation is continued.
The objective of this study is to observe the health effects of radiation exposure due torepain operations of the nuclear power plant accident. According to past studies, the biggest
concern is the increase in the incidence of cancer. However, the subjects are limited tothose who engaged in emergency operations immediately after the accident at the Fukushima
Nuclear Power Plant, and the total number is limited. When the observation target is limited
to cancer, the statistical power is not sufficient. If we make all cancers the study target, wehave to follow up for at least 40 years to detect a significant increase. It is also meaningful
to study the safety thresholds for future nuclear operations to ensure that no significant
increases are observed. However, instead of limiting the target disease to cancer, simultaneous
monitoring for more prevalent cardiovascular diseases should also be considered. Also,
attention should be directed to variables that are measured simultaneously in all target subjects
as continuous variables, such as blood pressure and many biochemical changes.

−89−

2. The Clinical Investigation Subcommittee (I)Subcommittee Chair, Co-Investigator: Waka Ohishi

Co-Investigator: Hiroko Kitamura

1.

Evolution of Research Objectives
1)

In the first phase of the Epidemiological Study of Health Effects in Fukushima
Nuclear Emergency Workers from fiscal years (FYs) 2014 to 2018, the Clinical
Investigation Subcommittee (Chair: Toshiteru Okubo) was established at theRadiation Effects Research Foundation (referred to as "RERF") as the lead institute.
The subcommittee conducted initiatives to encourage participation in the study andhealth examinations among emergency workers, as well as implementing nationwide
health examinations. In the second phase starting from FY 2019, with the relocationof the lead institute from RERF to the National Institute of Occupational Safety
and Health (referred to as "JNIOSH"), the research headquarter also transitioned
to JNIOSH. Therefore, in FYs 2019-2020, the Subcommittee I transferred the workof this epidemiological study to JNIOSH and provided support to the researchheadquarter at JNIOSH.

2)

In FY 2019, our objectives were to transfer tasks related to this epidemiologicalstudy to JNIOSH, assist and support tasks related to health examinations, and planand execute the transfer of paper documents, electronic records, and electronicstorage media related to epidemiological study collected and preserved in the firstphase at RERF to JNIOSH.

3)

In FY 2020, the objective was to plan and execute the transportation of biologicalsamples related to this epidemiological study collected and preserved in the firstphase at RERF to JNIOSH. Also, we aimed to conduct a pilot mail survey targeting
non-responders to the invitation to participate in this epidemiological study (those
who did not respond to previous invitations for study participation or healthexaminations), and transfer the survey operation to JNIOSH in FY2021.

4)In FY 2021 onward, with the assumption that the relationship between individual
exposure dose and the prevalence and incidence of non-cancer diseases such as
lifestyle diseases will be examined in the future, we aim to create an algorithm for
identifying individuals with non-cancer diseases.

2.

Summary of study results (major outcomes since the start of the study)< Publication of papers > K itamura H, Okubo T, Kodama K; Nuclear Emergency Workers Study Group.
Epidemiological study of health effects in Fukushima nuclear emergency workers -study−90−

design and progress report. Radiat Prot Dosimetry, 2018,182: 40-48.
 K
 itamura H, Ohishi W, Kodama K, Ohkubo T. Epidemiological study of health effects inFukushima Emergency Workers: Progress report on the Health Examination Study, 20162019. Environmental Advances 9 (2022) 100275.
< Presentation at academic conferences > Waka Ohishi: Epidemiological study of emergency workers at TEPCO Fukushima Daiichi
Nuclear Power Plant: Overview of Clinical (Health Examination) Study based on Experiencein the RERF Adult Health Study. The 2nd Epidemiological Study Conference for emergency
workers at TEPCO Fukushima Daiichi Nuclear Power Plant (Mar. 11, 2016)
 K
 itamura H, Kodama K, Okubo T. Epidemiological study of health effects in Fukushima
nuclear emergency workers—Study design and progress report. UNSCEAR Technical
Events in Japan to Present the Highlights of UNSCEAR Reports on Levels and Effects ofRadiation Exposure due to the Fukushima Accident. (2016.11.14-11.15)
 K
 itamura H, Okubo T, Kodama K. Epidemiological study of health effects in Fukushima
nuclear emergency workers (Nuclear Emergency Workers Study: NEWS)--Study design
and progress report. 15th Coordination and Planning Meeting of the WHO REMPAN
Collaborating Centers. (2017.7.3-7.5)
 Hiroko Kitamura: Epidemiological study of emergency workers at TEPCO Fukushima
Daiichi Nuclear Power Plant: Report on trends of study participants and the initiatives toencourage the participation in the study. The 4th Epidemiological Study Conference for
emergency workers at TEPCO Fukushima Daiichi Nuclear Power Plant (Mar. 14, 2018)
 K
 itamura H, Okubo T. Baseline Survey of the Epidemiological Study of Health Effects inFukushima Emergency Workers. WHO REMPAN Webinar "Public Health consequencesof Fukushima nuclear disaster: 10 years towards recovery". (2021.3.23)
 Hiroko Kitamura, Waka Ohishi, Kazunori Kodama, Hitomi Fujise, Shoko Kawanami,
Toshiteru Okubo. Epidemiological study of emergency workers at TEPCO Fukushima
Daiichi Nuclear Power Plant - Summary of the results of health examination in the 1stphase -. The 94th Annual Meeting of Japan Society for Occupational Health. (May 18-21,
2021)
 H
 itomi Fujise, Hiroko Kitamura, Misa Imaizumi, Michiko Yamada, Waka Ohishi, Toshiteru
Okubo. Epidemiological study of health effects of radiation workers - Mail survey. The 31st
National Council of Japan Society for Occupational Health. (Dec. 3-5, 2021)< Results from FY 2019 to 2020: Succession of research work from RERF to JNIOSH > W
 e created an attachment to the research plan regarding the method and procedure for−91−

transferring epidemiological research-related materials and biological samples that had
been collected during the first phase and stored at RERF to JNIOSH, obtained the approval
from the IRB, and carried out the work.
-- Transfer of documents: It was approved by the IRB on March 6, 2020, and thetransfer of paper documents, electromagnetic records, and electronic storage media
from RERF to JNIOSH was completed by the end of March 2020.
-- T ransfer of biological samples: It was approved by the IRB on November 20, 2020, andthe transfer of samples from RERF to JNIOSH was completed on December 2, 2020.
< Results in FY 2020: A pilot mail survey to encourage the participation in this epidemiologicalstudy among non-respondents > In preparation for full-scale implementation of the mail survey since FY 2021, a pilot
study was conducted with the following objective: (1) to understand the characteristics
of mail survey respondents, (2) to try and evaluate measures to improve response rates,(3) to link mail survey respondents to study participation and health examinations, and(4) to confirm whether there are any areas that need improvement in the questionnaire
for the mail survey.
-- T he response rate to the mail survey of the 913 individuals who have never responded
to previous mail invitations for study participation or health examination was 18.0%(164 individuals).
-- I n order to improve the response rate for future mail surveys, several measures wereconsidered, including sending a notice letter one week before the survey materials,
including a ballpoint pen with the materials, presenting Quo cards to respondents at
a later date, and sending a reminder postcard 10 days before the deadline.
-- A pproximately 99% of the 164 respondents to the mail survey answered an optionalquestionnaire, and 62.3% selected "wished to participate or cooperate in the study"as the reason for cooperating in the survey.
-- A mong the respondents to the optional questionnaire, 46.6% selected "I want to havea health examination of NEWS" and 15.5% selected "I want to know a little more
about it." 
B ased on the above, it was considered that the mail survey of non-respondents toencourage the participation in this epidemiological study is a method that contributes toimproving the rate of participation in the study and health examination.
 The mail survey operations were handed over to JNIOSH in FY 2021.

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< Results in FY 2021: Establishment of a process for identifying individuals with non-cancer
diseases (pilot study) > I n this epidemiological study, the relationship between individual exposure dose and theprevalence and incidence of non-cancer diseases such as lifestyle diseases is expected
to be investigated in the future. To achieve this objective, it is necessary to establish aprocess to more surely identify individuals with non-cancer diseases to be followed up.
 Therefore, in the fiscal year 2021, a pilot study was conducted with the aim of identifying
patients with hypertension and B/C type hepatitis, using the baseline survey data of all
subjects undergoing health examinations in this epidemiological study. The survey aimed
to (1) identify patients with the respective diseases and (2) compare them with those who
were self-reported in the self-administered questionnaire. An algorithm was developed
to extract patients with the respective diseases, and the usefulness of the algorithm wasevaluated by dividing it into two types: (1) prioritizing self-reported information and(2) prioritizing objective information.
-- The results showed that the algorithm prioritizing objective information may be
more reliable in identifying people with hypertension and hepatitis B/C. However,
because objective information such as blood pressure measurements and hepatitis
virus marker values can be affected by therapeutic interventions in all diseases, it wassuggested that combining information from a self-completed questionnaire (health andlifestyle questionnaire) on past and current history of illness, drug information, etc.,
is important for a more accurate identification of people with the relevant diseases.
 
Creating an algorithm to identify patients with non-cancer diseases is useful as a process,but the reliability of self-reported information is limited. Therefore, it is crucial tocarefully examine the contents of the data and select and combine appropriate objective
information to improve the accuracy of identifying patients with the targeted diseases.
< Objectives of the third phase >We will proceed with creation of an algorithm to identify patients mainly with non-cancer
diseases and precancerous lesions which are suggested to be related to radiation exposure
in atomic bomb survivors. At the same time, we will consider the method for evaluating theobjective accuracy and reliability of necessary objective information (imaging tests, etc.) for
the algorithm.

−93−

3. The Clinical Investigation Subcommittee (II)

Subcommittee Chair, Co-Investigator: Hokuto Hoshi

In investigating the long-term health effects of radiation exposure in emergency workers
involved in the Epidemiological Study of Health Effects in Fukushima Nuclear Emergency
Workers (NEWS), the Subcommittee II conducted a study to clarify confounding factors
such as employment and living background of emergency workers, social factors such asindustrial health and medical treatment environment, etc., and their health effects as well as
to understand the social background of the subjects required for medical examination andsubsequent guidance.
At the Third-Party Committee meeting in 2019, it was pointed out that "the handling ofconfounding factors is crucial to this study, and it should be clarified that the responsible
department is the research headquarters." In response to this, it has been confirmed that the
department responsible for handling confounding factors is the research headquarter at the
National Institute of Occupational Safety and Health (JNIOSH). Therefore, the researchheadquarters will select and review confounding factors in the final evaluation of major healtheffects such as radiation exposure. On the other hand, the Subcommittee II is intended toprovide information on the social factors of emergency workers and their actual conditions.
The results of this sub-study (Subcommittee II) will contribute to the research as reference
information for the entire study.
This sub-study has been continuously conducted from the start of the first phase of the NEWS
study, and the following contents and results are presented.
The first phase(1) L iterature research on employment and living background, etc. at the time of emergency
operations (FY 2015)(2)

Interview survey with business operators involved in the operations (FY 2015-2016)(3)

Summary of the above surveys and consideration of the method for classifying emergency
workers based on the survey (FY 2017)(4)

Pilot of a prototype questionnaire based on the above discussion (FY 2018)

The second phase(5)

Examination of the health effects of social factors by the existing questions (education
background, etc.) (FY 2019)(6)

Examination of the significance of the new questions (experience of evacuation, annual
income, etc.) as social factors (FY 2020)

−94−

(7)

Examination of the relationship between the new questions (experience of evacuation,
annual income, etc.) and exposure dose (FY 2021)(8)

Examination of the relationship between the new questions (experience of evacuation,
annual income, etc.) and BMI/blood pressure (FY 2022)

In addition, we are continuously conducting on-site surveys to confirm whether there areany events that could potentially affect clinical studies, such as trends in disease onset among
emergency workers.
In the study described in (1), we conducted a literature review of the employment andliving conditions of emergency workers mainly using press materials. However, there weremany unclear points.
In the study described in (2), we surveyed emergency operation personnel from 12
companies with a large number of emergency workers through interviews and written
responses.
Based on these results, in the study described in (3), we classified emergency workers into
the following four categories [1]-[4] based on their employment and living backgrounds.
[1] Temporal classification(1)

Super emergency operation period (around March 2011)(2)

Operation environment preparation period (around April to June 2011)(3)

Late emergency operation period (around July to October 2011)(4)

Decommissioning work period (November 2011 to present)[2] Employment pattern classification(1)

Long-term employment/long-term low-dose pattern(2)

Long-term employment/temporary high dose pattern(3)

Short-term employment/planned period pattern(4)

Short-term employment/dose limited pattern[3] Personal background classification(1)

Locally recruited(2)

Unaccompanied assignment(3)

Short-term worker−95−

[4] Employment status classification(1)

Still working and working on 1F at least once a week

(2)

Other workers(3)

RetiredSince some of them can be classified from the data obtained in the NEWS study, it isconsidered that the following two points should be newly confirmed in the clinical research.
(1)

Presence/absence of disaster-affected/evacuation life due to earthquake/nuclear
accident(2)

Employment status when engaged in emergency operations

We asked questions about the presence or absence of experience of evacuation, period of
evacuation, and state of returning home for the above item (1) and about the employment
status (no fixed term, fixed term, etc.,), presence or absence of specialist job, and annual
income at the time of emergency operation engagement (2011) for the above item (2) by thequestionnaire. We prepared an actual questionnaire and tested them in the study (4), andthe questions were included in the first follow-up survey.
"Evacuation experience" asked in this question refers to the fact that the respondents needed
to evacuate as residents due to the Great East Japan earthquake and the Fukushima Daiichi
Nuclear Power Plant accident in 2011. It was not about the evacuation under the operational
instruction by TEPCO, etc.
In the "baseline survey," the first clinical survey, questions were also asked about social factors
such as education background of emergency workers, contents of emergency operations, etc.
We first examined the relationship between the education background and clinical survey
results in order to examine the evaluation method for the effects of social factors in the future(study (5)). As a result, the following were found.
(1)

The education level greatly varies depending on the age of the target population
at the time of the earthquake. This seems to be an effect of the background of thetimes when respondents were students.

(2)

T he contents of emergency operations greatly vary depending on education
background. For example, those with junior high school as the education backgroundwere engaged in construction work more than others.

(3)Differences in education background were considered to be related to some blood−96−

test results, medical history, and blood pressure (systolic blood pressure) in particular.
(There was statistically significant difference in education background among allpairs of junior high school graduates, high school graduates, university graduates,and graduate school graduates (p < .001), and blood pressure was higher in thosewith lower education background.)(4)

Although the influence of age and lifestyle is considered to be great, a certain trend
was observed even after adjusting for age (particularly for systolic blood pressure),suggesting that education background may cause differences as an independent factor.

(5)However, education background is complicated in the first place and greatly varies
depending on employment and living background and the background of the times.
Therefore, it seems to be problematic to use it as a certain social factor in this study,
and other social factors that are evaluable from a perspective of natural science werenecessary.

(6) Many of the responses to the contents of emergency operations were "others,"suggesting that it was inadequate to estimate the radiation exposure from the resultsof this question. Other detailed dose evaluations were considered necessary to grasp
the individual doses.
In this study, the relationship between education background and blood pressure, etc. was not
examined by adjusting for information on lifestyle. If necessary for the study in the future, therelationship between education background and clinical survey results will be re-examined
after taking account of lifestyle factors.
In the study (6), we examined the validity of the questions (experience of evacuation andemployment status at the time of emergency operations, etc.) newly asked in the first followup survey based on the results of 383 subjects that we could summarize at the time of
preparation of the research report in FY 2020. As a result, the following were found.
(1) About 1/5 of the emergency workers may have experienced evacuation, and thehigher percentage of the workers seem to have experienced evacuation soon after
the earthquake (accident). (The percentage of subjects, who had experienced
evacuation life, started emergency operation engagement was 34% in March, 29%
in April, and 12-13% in May and after in 2011.)(2) Annual income is said to be a representative indicator of social factors that arequantitative and easy to evaluate, but its significance greatly varies depending onage, and therefore it is necessary to further investigate the evaluation method.

−97−

(Young people are mainly at the level of lower incomes. As the age rises, the income
increases. But it decreases again in older people.)
According to these results, we decided that the significance of social factors would be
evaluated in the future, particularly based on the response results of evacuation experienceand annual income at the time of emergency operations.
In the study described in (7), the relationship between the experience of evacuation andannual income at the time of emergency operations and cumulative exposure dose during
emergency operations was examined based on the results of 1,294 subjects in the first
follow-up survey aggregated at the time of preparation of the research report in FY 2021. As
a result, the following were found.
In the subjects of this study, the cumulative exposure dose during emergency operations
correlates with the annual income at the time of emergency operations and the presence/
absence of experience of evacuation. (The exposure dose is higher in the subjects withrelatively high income and experience of evacuation. (See Table 1))

Table 1

The distribution of cumulative radiation exposure by annual income and experience of evacuation at
the time of emergency operations (From the FY 2021 annual report)

Cumulative exposure dose for emergency operations (mSV)<5.0

Annualincome(10,000
yen)

Period ofevacuation
life
experience

<20.0

<50.0

50.0≤

n

Percentageof the total

<200

44

(53.0%)

28(33.7%)

11(13.3%)

0(0.0%)

83

6.5%

<400

79

(44.9%)

67(38.1%)

27(15.3%)

3(1.7%)

176

13.8%

<600

149

(47.2%)

103(32.6%)

44(13.9%)

20(6.3%)

316

24.8%

<800

171

(52.1%)

97(29.6%)

42(12.8%)

18(5.5%)

328

25.8%

800≤

195

(52.7%)

88(23.8%)

54(14.6%)

33(8.9%)

370

29.1%

Total

638

(50.1%)

383(30.1%)

178(14.0%)

74(5.8%)

1,273

None

576

(56.5%)

293(28.8%)

116(11.4%)

34(3.3%)

1,019

78.7%

Up to halfa year32(30.2%)

39(36.8%)

22(20.8%)

13(12.3%)

106

8.2%

Half a year
or longer38(22.5%)

60(35.5%)

44(26.0%)

27(16.0%)

169

13.1%

Total

646

(49.9%)

392(30.3%)

182(14.1%)

74(5.7%)

1,294

−98−

No certain trend was observed between age and cumulative exposure dose during emergency
operations.
Many subjects with relatively high annual income at the time of emergency operations hadhigh cumulative exposure dose at the time of emergency operations. This seems to be a resultof the fact that the career employee subjects such as the employees of TEPCO and those in
the managerial position continued to be involved in the site for a long period of time.
Also, the cumulative exposure dose at the time of emergency operations was higher inthose with experience of evacuation, suggesting that the local residents were more frequently
involved in the operations at the Fukushima Daiichi Nuclear Power Plant from the earlystage. (Many of the workers dispatched from other places seem to have left the Fukushima
Daiichi Nuclear Power Plant after completion of the outsourced operations.)
Based on these results, we consider that the annual income at the time of emergency
operations and the presence/absence of evacuation experience are factors that may be
relevant to the cumulative exposure dose at the time of emergency operations and need to
be examined in the evaluation of long-term health effects that will be revealed in the clinicalsurvey in the future.
In the remaining second phase, we will review the previous study results among all subjects
in the first follow-up survey and examine the relationship between the annual income, etc. at
the time of emergency operations, evacuation experience, contents of emergency operations(including exposure dose), and the results of health examinations, etc.
In addition, regarding the method of asking questions about social factors, it is planned to
examine how we should ask questions in the survey in the next phase.
In the future research, we are thinking of conducting a literature survey on socioeconomic
factors and health effects related to evacuation experience.
In the third phase, while clarifying how social factors unique to the study population suchas annual income and evacuation experience at the time of emergency operations are related
to the contents of emergency operations, we will promote the examination of whether thesesocial factors have effects on health. We will examine the actual evaluation method for thoserequired to be evaluated as confounding factors considering the independence from otherfactors in the health effect evaluation in the NEWS study. In addition, an on-site survey will
be conducted continuously to monitor the health status of emergency workers for any signsof change.
Survey on social factors, such as annual income, during emergency operations are based
solely on the responses obtained from the questionnaire. We did not obtain informationfrom official sources, so it is important to exercise caution with respect to the accuracy andobjectivity of the information. However, we selected these factors for the survey in order−99−

to achieve the objective of this study, which is to clarify the social background of the study
participants. Additionally, the NEWS study does not focus on socioeconomic factors per se.
Furthermore, there is no established consensus on what kind of socioeconomic informationis required to be obtained for the long-term health effect evaluation. Therefore, it iscurrently unclear what kind of questions or surveys can adjust for socioeconomic factors
appropriately in the long-term health effect evaluation. We will continue to investigate thesematters in future studies and examine the socioeconomic information necessary to achieve
the study objectives of the NEWS study.
Our hospital is located at a site where we can reach Fukushima Daiichi Nuclear Power
Plant, and we are one of medical institutions where clinical surveys (health examination) areconducted. We have been continuously conducting this sub-study by utilizing these factors
since the beginning of the NEWS study. However, as a general medical institution andnot an organization solely dedicated to research, it is challenging to establish an adequate
research environment. If the necessity for the study increases in the future, we believe that it
will be necessary to reevaluate the research organization of this sub-study.

4. The Analysis and Evaluation Subcommittee
1.

Subcommittee Chair, Co-Investigator: Shinji Yoshinaga
Study Objective

The primary objective of this subcommittee is to perform statistical analyses or evaluationsof accumulated study data in cooperation with other subcommittees.
2.

Initiatives for study topics

Since data for sufficient analysis have not been accumulated in this phase, among the items
pointed out by the Third-Party Committee in the first phase, we recalculated the statisticalpower to detect radiation exposure effects for each type of cancer including thyroid cancer as
particularly related to the analysis and evaluation.
3.

Summary of research results (outcome)Among approximately 6,000 participants who have participated in the study as of October
2021, the statistical power was calculated using a sample of 5,887 participants, after excluding
women, individuals with unknown sex, and those with unknown radiation doses. In thecalculations, we assumed the long-term follow-up and calculated the statistical power todetect the trend of increased risk according to the dose received during the emergency work
period for the incidence of major cancers by site (gastric cancer, colon cancer, lung cancer,−100−

prostate cancer, leukemia, and thyroid cancer) reported in previous studies, in addition to allsolid cancers combined.
The data we used included demographic information of the study participants, such as yearof birth, sex, and radiation dose (effective dose), as well as the national all-cause mortality
rates based on publicly available vital statistics and cancer incidence data based on national
cancer registry. The excess relative risk of cancer according to radiation dose was primarily
based on estimates reported in the Life Span Study of atomic bomb survivors. However,for thyroid cancer, since no radiation-related increase was shown in atomic bomb survivors
exposed in adulthood or most of the other epidemiological studies, a conservative assumption
was made, and estimates reported by Kesminiene et al. (2012) for Chernobyl clean-up workers
were used.
The calculation procedure involved first calculating the baseline cancer incidence, whichis the number of cancers that would occur regardless of radiation exposure. Based on a modelthat assumes cancer increases linearly with radiation dose, the amount of increase due toradiation was calculated. Finally, the statistical power for a one-sided test was calculated
based on the trend where the ratio of the baseline number and the expected total number(baseline plus radiation-induced number) increases with radiation dose increase.
For the calculation, we used the following assumptions: The 2018 mortality or cancer
incidence rate remained constant subsequently; the survey began for all study participantsin 2016; and the radiation-induced cancer risk remained constant regardless of ages. The
minimum latency period from radiation exposure to cancer development was not considered.
It was assumed that the following effects are negligible: The effects of confounding factors
related to smoking or other lifestyle habits, etc., the effects of medical exposure, occupational
exposure due to ordinary radiation operations, and environmental exposure. Since theestimated dose for each organ/tissue of the study subjects is not available, the effective dose
was assumed to be equivalent to the dose of each organ/tissue.
As a result, under the assumption the baseline incidence continued for 40 years at the samelevel, the predicted incidence, which was calculated by adding the baseline and excessive
amount due to radiation exposure, and the statistical power in the case of a follow-up periodof 40 years are shown in Table 1. The statistical power was 10% for all solid tumors andbelow 10% for other cancers by site.

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Table 1

Baseline Incidence, Expeted Total Incidence, and Statistical Power after 40-year
Follow-up

All solid Stomach Colontumors cancer
cancerLungcancer

Prostate
Thyroid
LeukemiacancercancerBaseline incidence

2,225

371.5

228.6

349.5

401.3

30.1

17.6

Expected Total
incidence

2,236

373

231

352

405

30.5

18.6

Statistical power

10.3%

6.7%

8.3%

7.1%

8.2%

6.5%

9.9%

The statistical power gradually increases with the increase in the number of years of followup and the number of participants. However, even if the number of participants was about
18,000, equivalent to 3 times the current number of participants, the statistical power was
calculated to be about 15-16% for all solid tumors and thyroid cancer and about 10% forother cancers. Also, we calculated the statistical power by increasing the value of the excess
relative risk per unit dose assuming an increase in cancer risk due to radiation exposure.
However, it was suggested that a high statistical power would not be ensured unless theestimated value of the excess relative risk per unit dose was approximately 5 or 10 times higher.
Since we assumed high risk estimates for thyroid cancer, the results should be carefullyinterpreted. Also, thyroid cancer includes a group with a very high dose in thyroid due tointernal exposure here, and therefore it is considered more important for the calculationconsidering the internal exposure. In addition, although we used a different calculation
method for the statistical power this time from the statistical power for all solid tumors
calculated in FY 2018, the results were mostly consistent.
The results of this statistical power calculation suggest that it is difficult to detect theincreased cancer risk of radiation exposure in this study unless the risk of cancer due toradiation is significantly higher than values obtained from the current findings. However,even if it is difficult to detect cancer risks related with radiation exposure, it is important
to continuously monitor the health effects of radiation in the only study population anddisseminate information on these results.
4.

Objectives of the third phase

In cooperation with other subcommittees such as the Cause of Death/Cancer Morbidity
Subcommittee and the Thyroid Cancer Investigation Subcommittee, we will evaluate thepotential effects of confounding factors and various biases and examine the handling of thesefactors in the analysis. Also, we will start an analysis of the relationship between radiation
exposure and health effects using the accumulated data.

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5. The Radiation Dose Evaluation Subcommittee

Subcommittee Chair, Co-Investigator: Makoto Akashi

Co-Investigator: Osamu Kurihara

Co-Investigator: Yumiko Suto

Co-Investigator: Norio Tsujimura

Co-Investigator: Takumaro Momose

Study objectives
The Epidemiological Study of Health Effects in Fukushima Nuclear Emergency Workers has
been carried out on the workers who were engaged in emergency operations just after theaccident at TEPCO Fukushima Daiichi Nuclear Power Plant. In this study subcommittee,
we examined the existing radiation exposure dose from the derivation process and evaluatedthe conversion factor to the dose of the target organs of the study and uncertainty ofradiation exposure dose aiming at refining the exposure dose of emergency workers usedin this epidemiological study. The biological dose was estimated using stable chromosome
aberration in some emergency workers and compared with the physical dose.
Initiatives for study topics
In the first phase of this research project (FY 2014-2018), our main focus was on examining
the re-evaluation method for physical dose and establishing a system for implementing
biological dose estimation. In the second phase of the project, we verified the personal dose
data of about 20,000 emergency workers provided by the Ministry of Health, Labour andWelfare through the National Institute of Occupational Safety and Health, Japan (JNIOSH),
which served as the lead institute. We also established the conversion factor from the value
indicated by the personal dosimeter used at the time of the accident to the dose in each organ(absorbed dose), and attempted to estimate the biological dose based on the frequency ofchromosomal translocation, which is a stable chromosome aberration, using blood samples
provided by participants in this study project. Furthermore, throughout the first and second
phases of the study project, we examined the analytical method for I-129 (physical half-life:
About 15.7 million years) contained in urine samples of about 230 emergency workers
collected at the time of the accident.
Summary of research results(1) Accuracy verification of direct thyroid measurements in high dose emergency workers
We conducted numerical simulations at the National Institute of Radiological Sciences(present National Institutes for Quantum Science and Technology) to assess the accuracyof the direct thyroid measurements at the time of the accident for six high-dose−103−(≥ 250 mSv) emergency workers who have been followed-up since immediately after theaccident. The simulations incorporated a numerical phantom prepared from individual
cervical MRI images and a detector model. Such a measurement is a method forquantifying the residual amount of gamma rays released from radioactive iodine (mainly
I-131) remaining in the thyroid using a radiation detector put close to the front of thepatient's neck. The use of a physical phantom to determine the detection efficiency ofthe detector can introduce errors in the evaluation of the residual amount of radioactive
iodine in the thyroid due to morphological differences between the phantom and theparticipant being measured. The results of the study confirmed that this measurement
error was within ± 20% considering the uncertainty of the position of the detector. On
the other hand, differences in individual thyroid volume were found to be significant
during the process of creating a numeric phantom, suggesting that it is an important
modifier when discussing the thyroid absorbed dose.
(2) Evaluation of effective dose and organ dose based on the values of electronic personal
dosimeterIt has been confirmed that the electronic personal dosimeter (ZP-1460) used at thetime of accident appropriately evaluated the effective dose based on the response test
at high dose rate (> 100 mSv/h) and rotating/isotropic irradiation tests conducted on ahuman body-shaped phantom. Additionally, the conversion factor was established frompersonal dosimeter values to effective doses or organ doses (red bone marrow, colon,lung, thyroid, crystalline lens) for the major gamma rays emitted by the nuclide that waspresent in the immediate aftermath of the accident. In the meanwhile, for beta rays notmeasured by the same personal dosimeter, in addition to the experimental evaluationof the attenuation rate by protective gears such as a full-face mask, we evaluated thebeta ray dose when the radionuclide that existed immediately after the accident waspresent on the ground surface as radioactive fallout by calculation simulation, taking
into account the radioactivity ratio of each nuclide and its change in time. The beta raydose greatly changes according to the height from the ground surface. The ratio of the
3 mm dose equivalent from beta rays, at the eye height of emergency workers, to the 1
cm dose equivalent from gamma rays, the value of the personal dosimeter, was evaluatedto be about 0.25 at maximum. However, the ratio is expected to be substantially lower
considering the absorption of beta rays due to the actual surface unevenness and theprotective effect of the full-face mask.

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(3) Verification and analysis of existing radiation exposure dose dataWe thoroughly examined several datasets related to the personal exposure dose of
approximately 20,000 emergency workers provided by JNIOSH, and constructed a
relational database that maintains the relationship between these datasets. F71 contains
published definitive values of emergency dose, F72 contains monthly dose values during
the emergency operation period, including external exposure dose (effective dose, eyelens dose, and skin dose) and internal exposure dose (committed effective dose), andF73 contains personal dosimeter data (indicated value) measured for each operation.
and they form a hierarchy. Additionally, there is TEC, which records internal exposure
dose data (measurement of residual amount of the detected nuclide in the body, date ofmeasurement, date of intake, method of measurement, etc.) of emergency workers fromTEPCO and cooperating companies collected by TEPCO.
 When the dose data of F71-73 was checked, the emergency dose in F71 almost
matched the total value of the monthly emergency dose in F72, but the monthly dosein F72 and the total value of the indicated values of the personal dosimeter during
the emergency operation in F73 did not match. This was because additional doses,
such as the stay dose in the anti-seismic buildings and travel dose from J village to
the Fukushima Daiichi Nuclear Power Plant, were separately added to the indicatedvalue of the personal dosimeter in F72. We confirmed that these doses were evaluatedindividually based on the length of stay and number of transfers. Furthermore, F72
contained external exposure doses, including effective dose (1 cm dose equivalent),
eye lens dose (3 mm dose equivalent), and skin dose (70 μm dose equivalent), andthe values were mostly the same. This was probably because the personal dosimeter
did not have sensitivity to beta rays as described above. Additionally, there was little
data available for the internal exposure dose (committed effective dose) of F72, and therecord level (2 mSv) was applied for TEPCO employees.
 The data on internal exposure dose in TEC was categorized into about 20 evaluation
methods based on various conditions such as the type of measuring equipment used, themethod of estimation when I-131 is not detected, the presence of additional measurements,
and individual evaluations. Verification calculations of the internal exposure doses were
performed using residual measurements in the body, dates of measurement, and dates
of intake. Results showed that internal exposure doses were reproducible for those who
detected I-131. When I-131, which greatly contributes to the internal exposure dose, was
not detected, one of the two methods was adopted to obtain a lower internal exposure
dose: (1) estimating the intake of I-131 by applying the ratio of the concentration ofradioactive substances of I-131 and Cs-137 in the air obtained from daily dust sampling−105−

at the Fukushima Daiichi Nuclear Plant to the intake of Cs-137 calculated from the invitro measurement; or (2) estimating assuming that the lowest detection limit of I-131 in
the in vitro measurement remained in the body at the time of measurement. However,for (1), since the sampling was performed only for a short time, the data were missingin the first week after the accident, and the ratio of radioactivity in the environment did
not necessarily coincide with the ratio of intake after inhalation, the uncertainty is large,
and for (2), overestimation is expected. Therefore, we extracted the emergency workers
in whom both I-131 and Cs-137 were detected, classified them into each fixed period
during March and April 2011 when exposure to I-131 was remarkable, calculated the
distribution of the ratio of intake based on the results of the in vitro measurement ofeach subject, and proposed a method in which the measure of central tendency is applied
to the persons in whom I-131 was not detected. As a result, a natural distribution ofinternal exposure dose (committed effective dose) was obtained, in which the number ofaffected individuals increased as the dose decreased. Also, based on the results, organ
doses due to internal exposure to thyroid, lung, colon, and bone surfaces were calculated.
(4) Biological dose estimation based on chromosome analysis
The degree of injury of chromosomes in peripheral blood lymphocytes was measured
to observe comprehensive dose throughout the life in both occupational and nonoccupational exposure.
 In this study, we conducted biological dose estimation using the frequency oftranslocation chromosomes, a form of stable chromosome aberration, as an indicator.
By the baseline survey (62 participants who underwent blood sampling in FY 2018), we
confirmed a positive correlation between the biological estimated dose and the external
exposure dose measured by personal dosimeters and also revealed that the history ofsmoking and medical exposure of participants was involved in the biological estimateddose. In addition, the frequency of stable chromosome aberrations increased withaging, suggesting the need for reinforcing the calibration curve using blood samples
from participants of different ages. Analysis of biological dose estimates for emergency
workers (blood samples collected from 54 participants in FY 2020) with external
exposure dose > 70 mSv is currently ongoing.
(5) Research on analysis of urinary iodine-129
Urine samples were collected from 517 emergency workers who underwent in vitro
measurements at the Japan Atomic Energy Agency at the time of the accident. Of them,the samples of 230 workers are still stored. If I-129 can be detected in these urine samples,−106−the amount of I-131 in urine at the time of collection can be evaluated from the iodine
isotope ratio (I-131/I-129) in the environment, and it may help in evaluating the internal
exposure dose of individuals without detection of I-131. However, the measurement of
I-129 requires the use of an accelerator mass spectrometry (AMS). Thus, we have beendeveloping an analysis method for that purpose. Iodine isolation in urine was attemptedusing ion exchange resin or CL resin, and iodine recovery rate was evaluated using
simulated urine samples. Actual urine samples will be analyzed using AMS in the next
fiscal year.
Objectives of the third phase
In the third phase, we will further strengthen cooperation with other study subcommittees
and JNIOSH, the lead research institute, build the dose database requested by each study
subcommittee, and make efforts to contribute to creation of study outcomes of the entire
epidemiological study aiming at further refining the dose evaluation, and evaluating theexposure dose and its uncertainty considering individual behavioral information.

6. The Cause of Death/Cancer Morbidity Investigation Subcommittee
1.

Subcommittee Chair, Co-Investigator: Kotaro Ozasa
Study objectives

The survey on the cause of death/cancer morbidity aims to track and confirm the survival
or death status of participants in the Epidemiological Study of Health Effects in Fukushima
Nuclear Emergency Workers and collect information on the cause of death and cancer
morbidity.
2.

Initiatives for study topics

In order to achieve the study objectives, informed consent for the follow-up items below has
been obtained (there are missing numbers in the items because they are excerpted from theinformed consent form).
(1) To be provided with documents related to the status of emergency operations, exposure
dose, and the results of statutory health examinations owned by TEPCO, contractors, andthe companies to which the participants were affiliated during the emergency operations.
(4) To check the residence records in accordance with the statutory procedures in order toobtain information such as the address after moving in the future, name after change due
to marriage, etc., and information necessary for checking and tracking survival or death.
(5) To be provided with the information on cancer morbidity from the local cancer registry of−107−

prefectures where the participants live or the national cancer registry of the National Cancer
Center. (6) To be provided with the past and future results of statutory health examinationsof the participants engaged in radiation operations from medical institutions. (7) To be
provided with the results of the detailed examination and related medical information ownedby the medical institution where the participants underwent the thyroid test (hematologic
test, ultrasonography, cytology, etc.). (9) In the case of death in the future, to be provided
with the information on death in the Vital Statistics (based on the death certificate) from the
Ministry of Health, Labour and Welfare through the statutory procedure and check it with
the information of the participant (name, date of birth, address, etc.) to investigate the causeof death.
Since this practice is mainly carried out at the time of health examinations, it has been
conducted at the headquarters. In order to determine the starting time for the follow up
which is required for the calculation of the follow-up person-years, it is necessary to
determine the time at which the emergency operations started and the time at which theworkers were withdrawn from the emergency operations. The current status survey andcontact at the time of making an appointment for health examination should be used to obtainfollow-up information such as address, and information regarding death or survival, etc. In
order to obtain outcome information (cause of death/development of cancer), informationon the cause of death in the Vital Statistics has been obtained since 2011, and informationof the national cancer registry has been obtained since 2016. In the former, there are issues
related to individual identification, and in the latter, there is a problem that it is limited to
explicit consenters, primarily consisting of participants who underwent health examinations.
3.

Summary of study results

A total of 6,221 participants underwent a baseline health examination from the beginning of
the survey to October 31, 2022. Of them, consent was acquired from 6,141 (99%) for (1),6,083 (98%) for (4), 6,149 (99%) for (5), 6,160 (99%) for (6), and 6,165 (99%) for (7).
Those who gave consent to (9) that was added after FY 2020 were 197 (63%) of 314 who
attended the baseline health examination during this period. The total number of participants
who gave consent including via postal mail and on the website and the percentage of the
19,812 emergency workers were 7,815 (39%) for (1), 7,657 (39%) for (4), 7,750 (39%)
for (5), 7,794 (39%) for (6), 7,785 (39%) for (7), and 4,103 (21%) for (9).
As for the follow-up of death/cause of death, the information on death in the Vital
Statistics for the generations relevant to the participants in this study between 2011 and theend of 2019 was issued according to the Statistics Act. When this information was collatedwith 4,103 participants who gave consent to the above item (9), only one death was identified.

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The small number of identified deaths was considered due to the short follow-up period
after consent was obtained. Since the layout of the cause of death data in the Vital Statistics
was changed in 2017, the collation software is currently being updated. For these reasons,the standardized mortality ratio was not calculated.
In order to follow up cancer morbidity, for 7,537 participants (7,526 men, 10 women,
and one person of unknown sex, up to the time of collation) who gave consent to the above
mentioned item (5), we applied for the use of the information of neoplasms (ICD-10:
C00-D48) diagnosed between 2016 and 2018 to the national cancer registry and obtained
the information. Of the participants, 140 men and <10 women had the first primary solidcancer (C00-C80) (in the case of less than 10 patients, the number is shown <10 because
the number is not disclosed, and the same applies hereinafter). Table 1 shows the numberof cancer cases with the major sites in men. Leukemia and lymphoma were observed in <10
men and no women, and cancer in situ of the colon and rectum (D010-D012) was observedin 16 men and no women. Benign neoplasm (D10-D36) was observed in <10 men and no
women, and neoplasms of uncertain or unknown behavior (D37-D48 including polycythemia
vera and myelodysplastic syndrome that are considered to have borderline characteristics)
were observed in <10 men and no women. There were <10 men and no women with thesecond or higher primary cancer.
The standardized incidence ratio (SIR) was obtained based on the incidence rates bycalendar year and by age in Japan during the same period as the standard rate, of which
information was published by the National Cancer Center (Table 1). First, the SIR for total
solid cancer was significantly higher. The point estimates for the SIR were 1.1 or higher(10% or higher than the reference population) for cancers of the stomach, liver, gallbladder,pancreas, prostate, kidney, urinary tract, and thyroid gland, and cancer in situ of the colonand rectum, and others, with statistically significantly higher values for cancers of theprostate and thyroid gland, and cancer in situ of the colon and rectum. On the other hand,the point estimate for the SIR was ≤0.9 in colorectal and lung cancers. The point estimates
for the SIR for cancers in other sites and leukemias/lymphomas ranged between 0.9 and 1.1.
These results indicate that SIR is high for cancers for which screening tests are performedin health examination and human dry dock (comprehensive health examinations), which isconsistent with the high SIR for cancer in situ. On the other hand, SIR for clinically detected
and unscreened cancers was generally not deviated from the national level. Therefore, it wasconsidered that the high SIR of cancer was likely to be due to excessive detection by healthexaminations in this study and voluntary health examinations. It will be necessary to examine
how many of them were found in the health examination of this epidemiological study.

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Table 1 N umber of cancer cases by site and standardized incidence ratio (SIR) in men,
2016-2018
Number of Expectedpatients
numberSIR (95% CI)

ICD code

Site

C00-C80

All solid cancer

140

108.3

1.29 (1.09, 1.53)

C16

Stomach19

16.6

1.14 (0.69, 1,79)

C18-C20

Colon and rectum

19

22.0

0.86 (0.52, 1.35)

C22-C25

Liver/gallbladder/pancreas

14

11.3

1.23 (0.67, 2.07)

C34

Lung

10

14.5

0.69 (0.33, 1.27)

C61

Prostate

26

13.8

1.89 (1.23, 2.78)

C64-C68

Kidney/urinary tract

15

8.5

1.77 (0.99, 2.91)

C73

Thyroid gland

16

2.0

8.01 (4.58, 12.9)

C00-C80 otherthan the above

Other sites

21

19.6

1.07 (0.66, 1.64)

C81-C96

Leukemia/lymphoma

<10

-*

0.91 (0.36, 1.87)

D010-D012

Cancer in situ (colon andrectum)16

8.7

1.84 (1.05, 2.98)

D00-D09 otherthan the above

Cancer in situ (other sites
except for colon or rectum)

<10

-*

1.24 (0.50, 2.56)*Not described because the observed number of patients was <10.
3.

Objectives of the third phase

Our goal is to obtain the results regarding cancer development within 15 years and deathwithin 30 years. To achieve this, we need to confirm the person-years of follow-up, especiallyfor confirming the beginning of follow-up. For this purpose, it is necessary to confirm theparticipants’ situation of engagement in operation and therefore, collaboration with the Dose
Evaluation Subcommittee will be necessary. In order to obtain follow-up information on
address, survival/death, etc., it is necessary to overcome the problem of missing information
on death during the current status survey or contact when making an appointment for healthexaminations. It is necessary to conduct a resident record survey within the record retention
period of deleted records at municipality offices. In any case, it is essential to conduct asimultaneous survival confirmation survey with confirmation of date of death at a certain
time point.
It is unrealistic to obtain consent from all participants (19,812) to investigate the causeof death. Significant bias may occur in the analysis of only participants with consent who
mainly underwent health examinations. Not only to avoid but also to evaluate such bias, it is−110−necessary to collect information on the cause of death in all participants including those notreceiving health examinations. Therefore, we need to establish a system to make information
on death and cause of death available for all participants.
It is unrealistic in practice to collect the information on cancer incidence until the end of2015 from local cancer registries in 47 prefectures because of a problem of transfer of cancer
registry information between prefectures due to the difference in the patient’s address andthe location of medical institutions providing medical care/submitting notification and aproblem of data quality due to differences in registry accuracy. Since the period from thenuclear power plant accident to 2016 is approximately 5 years, it is not considered to be
problematic to evaluate the radiation risk of solid cancers. However, for diseases such as
leukemia that increase in a short period after radiation exposure, other measures such as theuse of information on death should be considered.
The Analysis and Evaluation Subcommittee will discuss radiation risk analysis, butthere are challenges to determining person-years of follow-up, as well as challenges in the
Radiation Dose Evaluation Subcommittee regarding dose evaluation during emergency
operations and non-emergency situations, and how to combine and accumulate them. There
are also several radiation risk analysis-specific problems to consider, such as handling theexposure dose during emergency operations and doses during other period as time-dependent
variables. Additionally, there is a challenge in handling risk factors other than radiation thatare obtained from questionnaire surveys, as they may act as confounding factors. While theserisk factors can be collected from the participants in health examinations, it may be difficult
to obtain them from non-participants. Therefore, multiple imputation and other methods
are required. Furthermore, there is a problem how to deal with cancers that are excessively
detected by health examinations in this study, as well as in voluntary health examinations.
Generally, if there is no relationship between health examinations and exposure doses, overdetection of cancer by health examination only affects an increase in the baseline incidence
rate and does not affect radiation risk estimation. However, if participants exposed to higher
doses tend to undergo health examinations more frequently, the estimation of radiation risk
would be affected. In either case, the Analysis and Evaluation Subcommittee is thought toconduct a large part of the above analyses.

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7. The Thyroid Cancer Investigation Subcommittee

Subcommittee Chair, Co-Investigator: Tomotaka Sobue



Co-Investigator: Nobuyuki Taniguchi



Co-Investigator: Megumi Miyagawa

Study Objectives
The objectives of this study are: [Topic A] to collect and analyze the data of diagnostic
examination of those who were required to undergo the detailed examination in the "Studyon Thyroid Survey and Others in Workers of TEPCO Fukushima Daiichi Nuclear Power
Plant” of the Health Labour Sciences Research Grant 2013 Special Research Project (Chief
Investigator: Tomotaka Sobue; hereinafter referred to as the old study group) and the dataof previous thyroid ultrasonography in the exposure group and [Topic B] to examine themethod of implementing thyroid ultrasonography in the target population of about 20,000
emergency workers and collect and analyze the examination data.
Through these objectives, we aim to collect information on the health condition of
emergency workers and provide more detailed and accurate information on measures
for a nuclear power plant in an emergency. It is also expected that this study will provide
information to help the health management of the people engaged in occupations with thepotential exposure to radiation, such as nuclear power plant workers and emergency workers.
Initiatives for study topics
In this study, the following were conducted in response to Chapter II “the Suggestions for
the Study in the Second Phase” in the report of the Third-Party Committee in the first phasein 2019.
1.

Key points to be investigated: In the case of thyroid cancer, thyroid tests should be
performed by setting a control group with the same extraction rate including the lowdose group.

Response: To make the extraction rate the same for the low-dose group and the highdose group, health examinations will be encouraged to further increase the number of
examinees in the low-dose group. However, in the IARC expert report, thyroid screening
for the low-dose group is not recommended as the potential harms outweigh the benefits.
Therefore, it is not ethically appropriate to encourage them to undergo examinations.
Since the low-dose group originally has a larger population of participants, even if theexamination rate is lower, the number of examinees is still considerably higher than thatof the high-dose group. To address potential biases related to examination motivation,
we will conduct stratified analysis using indicators such as past thyroid ultrasonography−112−examination history, presence or absence of findings, family history, and other factors
related to health check-up attendance.
2.

Key points to be investigated: We would like to recommend that those with an abnormality
should undergo thyroid biopsy based on the same criteria and those with suspected results
should undergo active surveillance by thoroughly unifying the criteria to compare theresults.

 esponse: We have obtained consent from 127 specialized medical institutions nationwideRto perform secondary examinations, and if abnormalities are detected by ultrasound,
we refer or recommend patients to see physicians based on the same criteria. However,regarding individual cases such as tests and treatment options at each specialized medical
institution, we will only receive the results. We believe it is inappropriate to intervene inclinical decision-making.

3.

Key points to be investigated: In benign thyroid diseases, nodules and cysts are frequently
detected, and useful data are can be gathered as a result. The Japanese population is
known to have a high risk of latent cancer. This survey may provide new insights regarding
the natural history of thyroid nodules in adults. Subclinical hypothyroidism may beobserved in the group exposed to high doses.

Response: Thyroid cancer, hypothyroidism (including latent one), nodules, and cysts
are considered primary diseases and were mainly investigated. We developed diagnostic
criteria and conducted a comprehensive examination using ultrasonography, blood tests,
information from secondary examination from medical institutions, cancer registry data,and questionnaires.

These initiatives allowed us to collect detailed data and comprehensively examine theprimary diseases, including thyroid cancer.
Summary of study results
1.

[Topic A]

Concerning the data of the old study group, we obtained data for 627 out of 2,064 participantsfrom the National Institute of Occupational Safety and Health and checked the data of 531
participants who underwent thyroid ultrasonography (274 in the exposure group, 257 in thecontrol group). In the future, we plan to effectively utilize the data of the old study groupin conjunction with the Epidemiological Study of Health Effects in Fukushima Nuclear
Emergency Workers.

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To gather information on past thyroid ultrasonography, we included questions about past
thyroid diseases and ultrasonography history, obtained consent to contact medical institutions,and collected the information through questionnaires and consent forms. This fiscal year, we
counted the number of ultrasonography exams performed after emergency operations.
2.

[Topic B]

The Quality Control Committee has been established at Jichi Medical University. This
Committee is engaged in the development of technicians involved in thyroid ultrasonography,
central review of ultrasonography findings, and referral of those requiring the secondary
examination to specialized medical institutions. We provide the training seminars forbeginners and experienced technicians twice a year and try to improve skills and knowledgeof thyroid ultrasonography. Also, we certify technicians and health examination institutions
that meet certain criteria as certified technicians and certified institutions. As of December
2022, there are 113 certified technicians and 40 certified institutions. In addition, we havebeen conducting a central review for all participants since April 2017 and sending theresults to each health examination institution. Regarding those requiring the secondary
examination, we aim to obtain more accurate information by referring them to specialized
medical institutions and collecting the results. Through these initiatives, the examinations
are conducted while improving and maintaining the accuracy of thyroid ultrasonography ofeach health examination institution.
As of the end of October 2022, out of 6,203 participants in the baseline survey, 4,779(77.0%) consented to undergo thyroid ultrasonography, and out of 2,540 participants inthe longitudinal survey, 1,920 (75.6%) consented to it. In both surveys, the percentageof participants who visited medical institutions where ultrasonography was not available
was higher in the low-dose group, and the percentage of participants who consented to theexamination tended to be higher in the high-dose group. Overall, the non-consent rate was
low at 0.5%.
Regarding the implementation rate of the central review, in the baseline survey, 3,284
participants (16.6% of the 19,808 emergency workers and 52.9% of the 6,203 examineesof health examinations) underwent the central review. In the longitudinal survey, 1,916
participants (9.7% of the 19,808 emergency workers and 75.4% of the 2,540 examinees ofhealth examinations) underwent the central review. There was a tendency toward a higher
rate of the central review by ultrasonography in the high-dose group.
Regarding the final diagnosis of thyroid ultrasonography, the percentage of B diagnosis(requiring secondary examination) was 15.5% in the baseline survey and 16.8% in thelongitudinal survey, and there were no cases of C diagnosis. Both the baseline and longitudinal−114−

surveys showed that the percentage of B diagnosis tended to increase with age, and no clear
increase in the percentage of B diagnosis was observed in the high-dose group.
Regarding the receipt rate of the secondary examination results in participants assessed
as B/C, in the baseline survey, 39.2% of participants assessed as B received the secondary
examination results and 74 (37.2%) of them underwent cytology. The results of cytology
were confirmed in 72 participants. Cytology results were confirmed in 14.2% (72/508) ofparticipants assessed as B, and of those, 5 were diagnosed with cancer or were suspected ofhaving cancer. In the longitudinal survey, 45.0% of participants assessed as B received thesecondary examination results, and 29 (20.0%) of them underwent cytology. The resultsof cytology were confirmed by 23 participants. Cytology results were confirmed by 7.1%
(23/322) of participants assessed as B, and of those, 2 were diagnosed with cancer or weresuspected of having cancer.
The diagnostic criteria for the cumulative incidence of thyroid cancer were 1) definite
diagnosis based on information from medical institutions or cancer registry, 2) malignancy
confirmed by cytology, or 3) suspicion based on the patient’s history of thyroid cancer
as reported in a questionnaire. The study analyzed 6,199 health examination examinees,
excluding 4 participants with a history of thyroid cancer before the earthquake. The cumulative
incidence of thyroid cancer after the earthquake was 30 (7 definitive and 23 suspectedcases), with a cumulative incidence of 0.5%. The same rate was observed in participants
who underwent central review of ultrasonography. Age of the participants diagnosed withthyroid cancer were mostly in their 30s to 50s at the time of the earthquake (many of theparticipants were in their 30s to 50s). The incidence tended to be higher in those who were
exposed to an effective dose of 50 mSv or higher. Furthermore, 20% of the patients werediagnosed within 5 years after the earthquake, 60% were diagnosed between 5 and 10 years,
and 20% were diagnosed 10 years or more after the earthquake. Finally, we examined thenumber of thyroid ultrasonography tests after emergency operations as a factor related tothe diagnosis of thyroid cancer. The results showed that participants with higher radiation
exposure had more frequent ultrasonography tests and a higher chance of being diagnosed
with thyroid cancer.
The diagnostic criteria for hypothyroidism were defined as a TSH level above the reference
range and a Free T4 level below the upper limit of reference range, or self-reported
treatment for hypothyroidism or current use of thyroid hormone medication as reported in
the questionnaire (except being treated for thyroid diseases other than hypothyroidism, ahistory of thyroid surgery, or a history of neck radiotherapy). Participants who underwent
a thyroid blood test were tabulated. Among 6,192 participants who underwent the baseline
survey, the prevalence of hypothyroidism was 3.5%. The prevalence tended to increase as−115−

the age at the time of examination increased, but there was no clear association between theeffective dose level and prevalence.
The diagnosis of nodules was based on the presence of a nodule or cystic nodule with alargest diameter of ≥ 5.1 mm on the primary examination (ultrasonography). Among the
3,284 baseline survey participants who underwent central review of ultrasonography, theprevalence of nodules was 15.2%. The prevalence tended to increase with age at the timeof examination, but there was no clear association between the effective dose level andprevalence.
Cysts were diagnosed using the same criteria as nodules, with a largest diameter of ≥5.1 mm on the primary examination (ultrasonography). Among the 3,284 baseline survey
participants who underwent central review, the prevalence of cysts was 11.3%, and theprevalence tended to increase with age at the time of examination. However, no clear
association was found between the effective dose level and cyst prevalence.
Objectives of the third phase
The objective of the third phase is to confirm whether or not important data are missing
and establish a system for long-term observation by updating the health examination andanalyzing all currently available data, with a focus on the results of ultrasonography andthe primary endpoint. In order to increase the rate of acquisition of secondary examination
results, it is important to establish a system for tracking whether or not participants haveundergone secondary examination and take measures to increase the rate of result acquisition.
Additionally, while reducing the burden on health examination institutions associated withultrasonography and introduction of secondary examinations, we will establish a system todetermine the incidence of thyroid cancer by cross-checking with the national cancer registry
in cooperation with the Cause of Death/Cancer Morbidity Investigation Subcommittee, andthen select examination participants and analyze the results based on re-evaluation of thedose of thyroid radiation in cooperation with the Dose Evaluation Subcommittee.

8. The Cataract Investigation Subcommittee

Subcommittee Chair, Co-Investigator: Hiroshi Sasaki

Study objectives
The crystalline lens is one of the tissues in the human body that is highly sensitive toradiation, and it has been reported that cataract is caused by exposure to the low-doseradiation even lower than the threshold previously considered. The Cataract Investigation
Subcommittee is intended to conduct a cataract survey in emergency workers and clarify−116−the relationship between radiation exposure and the onset of cataracts through long-term
follow-up observation.
Initiatives for study topics
The Cataract Subcommittee conducts two surveys in parallel. One survey has been conducted
every year since 2013 for current TEPCO employees with an effective dose of > 50 mSv.
The screening is conducted at 3 sites: Fukushima Daiichi and Daini Nuclear Power Plants,
Kashiwazaki Kariwa Nuclear Power Plant, and Tokyo Head Office. The diagnosis of cataracts
was made by the combination of diagnosis by slit lamp microscopy by ophthalmologists anddiagnostic imaging by using two cameras (anterior eye segment analyzer EAS-1000 (NIDEK)
and simple retroillumination camera (LOVEOX)), and both were performed under mydriasis.
The other is a nationwide survey of participants across in Japan, conducted at ophthalmic
clinics. This study began in 2018 and was designed to have one course every three years.
The 1st course was conducted between FY 2018 and FY 2020, and the 2nd course is being
conducted between FY 2021 and FY 2023. We are in the 2nd year of the 2nd course. The
survey is conducted at 71 ophthalmic clinics in Japan with the cooperation of JapaneseSociety for Cataract Research and Japan Ophthalmologists Association. The diagnosis of
cataracts was made by ophthalmologists under mydriasis, and a simple retroillumination
camera is also installed at some clinics to take images of crystalline lenses. The final assessmentof the test results (findings and lens images) diagnosed in the two surveys was made by the
Quality Control Committee of Kanazawa Medical University.
Cataracts were evaluated based on the classification by Merriam & Focht (1962), which isa diagnostic criterion of radiation cataract, using a six-type categorization system. It included
3 main types (cortical, nuclear, posterior subcapsular) that lead to a deterioration of visualfunctions, 2 subtypes (Retrodots [RD] and Waterclefts [WC]), and minute opacities that areconsidered to be an initial change in radiation cataracts (Vacuoles [VC]). Localization (presenceor absence of central posterior subcapsular) was also evaluated for VC (see Figure 1).
Ophthalmologists performing diagnoses were provided with a diagnostic manual for the 6types of cataracts and used a table of findings for entering descriptions to ensure consistentevaluation. In general ophthalmic practice, macroscopic diagnosis by an ophthalmologist
with slit-lamp microscopy is the standard, but we believe that retroillumination images witha crystalline lens camera are also essential for follow-up of such minute opacities. We havealso developed an automated crystalline lens opacity measurement system that uses deeplearning-based image recognition processes to detect cataracts based on retroillumination
images. We are currently working on creating a universal evaluation for the final judgment.

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Figure 1. Types of cataracts to be examined in this study
Summary of study results
The survey of the TEPCO employees, which was suspended in 2020 and 2021 due to the
influence of the COVID-19 pandemic, has resumed from FY 2022. In addition, image analysis
of past screening data has been initiated. First, data of participants who provided consent tothis study are being tabulated and extracted to investigate the prevalence of the 5 types ofcataracts and VC (minute opacities). We also plan to investigate the 7-year follow-up of thesame participants.
In the nationwide survey, 497 participants (mean age: 54.2 ± 10.0 years) were enrolled in
the 1st course. Of these, 26.4% had clear eyes (no cataracts) without minute opacities such as
VC. Those with an initial change in radiation cataract, including VC and cataracts, accounted
for 73.0%, and 0.6% had intraocular lenses after cataract surgery. Of the 363 subjects
diagnosed with cataracts, 90.1% had corrected visual acuity of > 1.0, 7.9% had visual acuityof 0.7-0.9, and 2.1% had visual acuity of < 0.6. These results indicated that nearly 90% of thestudy participants, 8 to 10 years post-accident, did not have cataracts or had changes in theircrystalline lenses but still had good visual acuity (see Figure 2). The prevalence of VC in thecentral posterior subcapsular of crystalline lenses was 8.3% in the 30s and 12.7% in the 40s.
It is particularly important to track changes in posterior subcapsular VC in people in their
30s and 40s. One hypothesis for the current threshold dose set by the ICRP is that all minuteopacities progress to visual impaired cataracts at least 20 years after radiation exposure.
Observing young participants could help verify this hypothesis, but since the 20-year period
may also cause age-related cataracts, a careful examination is necessary. Currently, the 2nd
course is ongoing. Approximately 7,000 participants who provided consent and cooperationin the Epidemiological Study of Health Effects in Fukushima Nuclear Emergency Workers(NEWS)The target subjects of the 2nd course were approximately 7,000 for whom we obtained−118−

consent to /cooperation in the NEWS study, and the guide letters of screening were sent
to them. 3,504 subjects answered that they wished to undergo the screening. Of theseparticipants, approximately 2,500 were eligible for screening. 1,474 of them were screenedin 2021 and 2022, and the remaining 1,000 are scheduled for screening in 2023.

Figure 2. Results of 1st course
Multicenter studies such as nationwide surveys require a large amount of data analysis
and follow-up based on image data. To enable objective evaluation, it is urgently necessary
to establish an automatic analysis system for crystalline lens opacities. With regards to themodel for VC detection, we have improved its accuracy by analyzing a large number ofimages from TEPCO screening. Moreover, we are increasing the versatility of the model tomake it useful in wider range of screenings as a model specialized in radiation cataract.
Objectives of the third phase
The cataract survey will continue in the third phase of the NEWS study, as in the current
phase. The nationwide survey will start the 3rd course. We will install simple retroillumination
cameras in many facilities, and we will also consider transferring cameras between facilities
in prefectures with a small number of participants to take as many crystalline lens images as
possible. In addition to conducting a detailed examination of these cataract survey results, itis necessary to examine the relationship between cataract survey results and exposure dosein past data analysis.

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9. The Psychological Impact Subcommittee

Subcommittee Chair, Co-Investigator: Hisashi Eguchi



Co-Investigator: Kosuke Mafune

We examined the psychological effects of emergency workers by using the questionnaire andinterview in the "Study on the assessment of psychological effects on radiation operation
workers” (first phase survey for 5 years from 2014 and second 5-year phase from 2019 ). We
reduced variation by interviewers in the interview survey through construction of a survey
implementation system that enables us to cope with a large number of subjects.
[Questionnaire survey]
Of the 5,249 responses returned by October 31, 2022, the questionnaire survey included
4,735 subjects who provided consent to participate in the study and whose data were collatedwith the attribute information. Only the initial survey of each subject was analyzed in thisreport. In the questionnaire survey, we used 4 scales as outcome indices: Psychological stress(K6), alcohol-related problems (AUDIT), insomnia symptoms (AIS), and post-traumaticstress disorder (PTSD) symptoms (IES-R). As exposure variables, we also asked the subjects
to answer the beginning of the emergency work at TEPCO Fukushima Daiichi Nuclear
Power Plant, duration of the work, and type of emergency operations. The following 9 scales
were used as adjustment variables assumed to be associated with mental health: Defamation
or discrimination associated with emergency operations (stigma), life events in the past
1 year from the time of the survey, social support at 2 time points: At present and at thetime of emergency operations, stress coping (BSCP), sense of coherence (SOC3-UTHS),
resilience (CD-RISC2), self-efficacy, self-esteem, and life/job satisfaction. The prevalenceof psychological stress (K6) and insomnia symptoms (AIS) did not markedly differ fromprevious studies in Japanese workers. Psychological stress, insomnia symptoms, alcoholrelated problems, and PTSD symptoms were found to be significantly associated with stressrelated factors such as stigma, life events, social support, part of stress coping, self-esteem,
and work/life satisfaction. In particular, stigma showed the same strong association as in
the previous studies. It was also suggested that social support in emergency operations isimportant as a protective factor for the mental health of workers even taking into accountthe influence of stigma and life events. In particular, social support by the superiors at thetime of emergency operations was considered to be an important protective factor when the
period of emergency work extended longer than 30 days.
[Interview survey]
In the interview survey, we analyzed 3,504 subjects (3,489 men, 3 women, and 12 unknown)−120−

who underwent the health examination survey by October 31, 2022 and provided valid
responses in the interview survey. In order to reduce evaluation variability of interviewers,
we adopted a structured interview and used the Computer-Assisted Personal Interviewing(CAPI) of the World Health Organization Composite International Diagnostic Interview(WHO-CIDI). In this study, we used only the depression module from WHO-CIDI toevaluate the prevalence of depression and used 2 criteria, American Psychiatric Association's
DSM-IV-TR and WHO's ICD-10, to evaluate the depression findings during the past 1
month, last 12 months, and lifetime from the time of survey. The prevalence of "major
depressive disorder" (296.xx) in DSM-IV-TR was 0.2% (n=8) in the last 1 month, 1.9%
(n=66) in the last 12 months, and 6.9% (n=242) in the lifetime. The prevalence of "severe
depressive episodes without psychotic symptoms" (F32.2, F33.2) in ICD-10 was observed tobe 0.1% (n=5) in the last 1 month, 1.1% (n=37) in the last 12 months, and 3.3% (n=117)
in the lifetime. In the large-scale preceding study in Japan, the prevalence according to thecriteria of DSM-IV-TR and ICD-10 was 4.3% and 2.3% in the lifetime, 2.2% and 0.9% in
the last 12 months, and 0.3% and 0.1% in the last 1 month, respectively. Although it wascomparable to this study over the last 1 year, the lifetime prevalence was slightly higher
in this study. It should be noted that since only the depression module of the CIDI was
excerpted and used in this study, there was an issue that the age at relapse could not beadequately estimated. In FY 2022, the age calculation method was improved and accordingly,
the estimation of the time of relapse was improved. As previously reported, incidence ofdepression after disaster was significantly higher in those with history of depression before
disaster. As a result, it was suggested that the strength of the association was underestimatedbefore the program was improved. In addition, based on ICD-10, the lifetime prevalence andincidence after the disaster were significantly higher in the exposure group with an effective
dose of > 100 mSv.
[Implementation system for interview survey]
In this study, in order to examine the relationship between emergency operations and mental
health, we emphasize the combination of a valid interview method that can identify the timeof onset of symptoms. We examined the existing structured interviews in FY 2014 and 2015
and decided to adopt the depression module of the CAPI of WHO-CIDI. In addition, we
have been continuously providing training programs to develop the interviewers so that theinterview survey can be conducted at the study cooperation institutions in throughout Japan.
In FY 2020, due to the influence of the COVID-19 pandemic, it became difficult to continue
structured interviews at the time of health examinations conducted at the study cooperation
institutions. From the latter half of FY 2021, a centralized health survey trial was conducted,−121−which enabled us to interview a larger number of participants at one time. Thus, in order toestablish a system to ensure sufficient accuracy of the survey and to conduct the survey
nationwide, we outsourced the implementation of structured interviews to an institution
specialized in this survey, which allowed us to conduct high-quality surveys in a stable manner.
They provide periodic training for interviewers who can continuously conduct the survey.
Outsourcing of a large-scale survey can also contribute to reducing the burden of study
cooperation institutions that cannot allocate dedicated staff for the interview survey. In FY
2022, we provided the education and training specified by WHO-CIDI and further improved
the sustainability of structured interview surveys to increase the number of interviewers who
can respond to the actual survey in the metroporitan region and secure the quality.

10. The Health Management Database Subcommittee

Subcommittee Chair, Co-Investigator: Akira Ogami◆ Background and Objectives of the Subcommittee's Establishment
The overall objective of this Epidemiological Study of Health Effects in Fukushima Nuclear
Emergency Workers is to conduct detailed health checkups over the lifetime to investigate
health effect of radiation over the long term in a comprehensive manner. The health datacollected in this study are expected to contribute to the maintenance and improvement of thehealth of emergency workers through health guidance to study participants. However, there
is currently no established protocol for providing health guidance and explaining the results
to health examination participants who expressed their intention to undergo the examination.
Therefore, we have decided to establish a subcommittee from the second phase of the study
to develop an effective feedback system for the summarized health management database of
the operation workers and to study how to lead it to continuous and effective use.
◆ What have been conducted in this study(1) Survey of the actual status of acceptance criteria in medical institutions conducting
health examinations for this epidemiological study (2020-2021)W e obtained the notifications of health examination results from 45 medical institutions
nationwide participating in this epidemiological study and compared with the reference
values of each test item listed in there (reference values that give some alert as presenceof findings).
(2) Creation of a risk matrix for health assessment based on health examination data (20202021)
W ith the aim of conducting a comprehensive "health assessment" using health−122−examination data, we attempted to create a risk matrix based on the anonymous healthexamination data of participants who underwent multiple-item health examination andbasic health examination in the epidemiological study regarding the health effects ofradiation workers that was conducted up until 2020.
①

In multiple-item and basic health examinations, health examination items wereclassified by system into 10 groups (obesity/emaciation, blood pressure, liverfunction, glucose tolerance, lipids, renal function, inflammation, anemia or
polycythemia, ECG, and chest X-ray), and the reference values were set for healthexamination items in each group based on the frequency distribution of test values.

②

The risk items were classified into 3 groups: "Low risk group,” "medium risk group,"and "high risk group" according to the reference values, and the risk levels were
determined by the reference values set among the 10 risk items.

(3) Longitudinal examination of the DATABASE using risk matrix: Risk Distribution when
Applied to Basic and Multiple-item Health Examination Data (From 2021)
The risk assessment obtained from the risk matrix in (2) was applied to the data of 885
participants who underwent basic health examinations in FY 2019 and 1,564 participants
who underwent basic health examinations in FY 2020 and were registered in an online
community. Participants who had data for both years were defined as ‘continued
participants’, and their risk assessment and analysis of changes in data were conducted
for each year.
 Regarding the annual changes in 2019 and 2020, we evaluated the following items
as numerical values: (1) obesity/emaciation (BMI), (2) blood pressure (systolic bloodpressure: BP-s) (diastolic blood pressure: BP-d), (3) hepatic function (AST/GOT,
ALT/GPT, γ-GTP), (4) glucose tolerance (BS), (5) lipids (HDL, LDL, TG), and(6) inflammation (WBC). We calculated the increase/decrease from 2019 to 2020 asdelta for each individual and tabulated it by risk group in 2020. As a result, in terms ofobesity/emaciation, the high risk group in 2020 showed an average increase in BMI of
0.20 kg/m2 compared to the previous year, while the medium risk group showed almost
no change at -0.03 kg/m2, and the low risk group decreased by -0.20 kg/m2. Similarly,
the high risk group showed a positive increasing trend in blood pressure, hepaticfunction, and triglycerides from the previous year.
(4) Development and production of health examination DB app (from 2020)R egarding the system for feedback of health examination results, we formulated design
guidelines for the following items, and at the same time, prepared draft specifications.
A.	System operating environment requirement definition, security requirement
definition−123−B1. Establishment of operation flow
B2. Design of a function of sending and receiving emails
B3. System functional configuration design
B4. Formulation of types of information to be processed
C1. Design of content/forms of history taking
C2. Specifications/functions of data import
C3. Import specifications/functions for past health examination data
D1.	Health examination results format specifications/processing function design
D2.	Development of individual data assessment techniques and expression
methods
 For an overview of the application, registrants enter through the login screen. After
logging in, they move to the authentication screen. For the first-time authentication,
they enter a confirmation key to proceed to the menu screen. To view health examination
data, they click on the corresponding tab to access the health examination item screen.
Clicking on any item displays the data graph screen, which allows registrants to checktheir own data transitions. The 'Assessment Based on Health Examination Data' tab on
the menu screen uses the 'Risk Matrix for Health Examination Data' to provide a new
way of assessing health based on risk items identified during the examination. Medical
descriptions of test items are also prepared as content. On this screen, 10 risk items are
displayed using colors to indicate low (blue), medium (yellow), and high (red) risk. The
background colors are shown as overall assessment, and they are presented in a similar
way by using colors.
◆ Goals for the remaining one year of the second phase
The plan for the remaining year is to conduct a pilot application demonstration, verify theoperability and security, and revise it towards full-scale operation. We will also conduct
verification of the validity of the risk matrix.
◆ Objectives for the third Phase
We will actually use the app and disclose the results of health examinations to theparticipants who expressed their intention to undergo health examinations, and we willcontinue to verify the validity of the risk matrix based on the analysis results of longitudinal
basic health examination data. Thus, we aim to contribute to the maintenance andpromotion of health of emergency workers through health guidance for study participants.

−124−◆ What hindered the progress of the study
The number of entries of examinees undergoing health examination increases or decreases
depending on the year of health examination, and there is still room for improvement in theaccuracy of data from various health examination institutions. These are the issues that seemto be hindering the progress of the study.
◆ Proposal for future improvements
In this study, we will examine new decision logic for detecting abnormalities in healthexamination items based on data from previous examinations, including questionnaires.
We anticipate that in the future, we will be able to explore areas not typically covered inconventional health examinations. Therefore, it is important to present a step-by-step plan
to health examination participants regarding what analysis results will be provided based on
the health examinations, as well as what information will be obtained in the future.
Also, it is necessary to construct the implementation system of a health examination
app after obtaining "consent to participation" based on a full understanding after giving
an explanation. Thus, it is considered necessary to improve data management, system
maintenance, service response, etc. as a study infrastructure.

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