Guideline on Ethical Procedures for Submitting Presentations to theJapanese Society of Oral and Maxillofacial Surgery, Second Edition

April 22, 2024
Public Interest Incorporated Association, Japanese Society of Oral and Maxillofacial Surgeons1Table of Contents
I

Introduction

II

Invasive Study

III

Interventional StudyIV

Observational Study

V

Case Report

VI

Ethical Guidelines for Genetic Analysis ResearchVII

A Study Not Requiring Ethical Review, Permission of the Institutional Head, or Informed

Consent (IC) from Study Subjects
VIII

Algorithm for Determining Study Type

IX

Compensation for Medical Research (Clinical Research Insurance)X

A Study Not Involving Human Subjects

2

I．

Introduction

Research presented at the Japanese Society for Oral and Maxillofacial Surgery must comply withrelated laws and regulations, including the Declaration of Helsinki, "Ethical Guidelines for Biomedical
and Medical Research Involving Human Subjects (Life and Medical Guidelines)," "Ethical Guidelines
for Medical and Health Research Involving Human Subjects," "Guidelines for Clinical Research ofGene Therapy, etc.," "Clinical Trials Act," "Act on Securing Safety of Regenerative Medicine, etc.,"
and "Act on Securing Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, Regenerativeand Cellular Therapy Products, Gene Therapy Products, and Cosmetics (PMD Act)" established by
the Ministry of Education, Culture, Sports, Science and Technology (MEXT) and the Ministry of
Health, Labour and Welfare (MHLW). The Ethical Guideline for Research by the Japanese Society ofOral and Maxillofacial Surgery was prepared based on the Ethical Guidelines established by the
MEXT, the MHLW, and the Ministry of Economy, Trade and Industry, as well as referencing the
Ethical Guidelines established by the Japan Digestive Disease Week (revised on September 27, 2022;
available on the Japan Digestive Disease Week website: https://www.jddw.jp/meeting/rinri.html), with
provisions for future revisions as necessary. Presenters at the Japanese Society for Oral andMaxillofacial Surgery must adhere to this guideline and conduct themselves appropriately per the
ethical guidelines of their respective institutions. In this context, the dignity and human rights of study
subjects must be protected. However, this ethical guideline is not intended to impose constraints orlimitations on the research activities of presenters at the Japanese Society of Oral and Maxillofacial
Surgery and serves only as a framework for researchers to conduct a wide range of ethical research
activities, prioritizing the welfare of research subjects.
This ethical guideline functions as a code that researchers must comply with to facilitate medical
research responsibly while respecting the dignity and human rights of research subjects. It wasdeveloped primarily following the "Ethical Guidelines for Life Science and Medical Research
Involving

Human

Subjects"

available

on

the

MHLW

website(https://www.mhlw.go.jp/stf/seisakunitsuite/bunya/hokabunya/kenkyujigyou/i-kenkyu/).

However,

for research governed by the "Guidelines for Clinical Research of Gene Therapy, etc.," "Clinical Trials
Act," "Act on the Safety of Regenerative Medicine, etc.," "Pharmaceuticals and Medical Devices Act,"etc., strict compliance with these guidelines and laws is necessary. (Category E in Figure:Classification of the presentations submitted to the Japanese Society of Oral and Maxillofacial
Surgery). Additionally, compliance with applicable laws such as the "Clinical Trials Act" and the "Acton the Safety of Regenerative Medicine, etc." is required for research (Categories D1, D2, and E in
Figure: Classification of the presentations submitted to the Japanese Society for Oral and Maxillofacial
Surgery).

3

II.

Invasive Study (Categories B2, C, D1, D2, and E in Figure: Classification of thepresentations submitted to the Japanese Society for Oral and Maxillofacial Surgery)1.

Definition of "invasiveness"
Actions such as puncture, incision, drug administration, radiation, and questions touching upon

trauma conducted for research purposes (Note 1), resulting in physical or mental injuries or burdens
to the subject. "Minimal invasiveness" refers to those aspects of invasiveness where the resulting
physical or mental injuries or burdens to the subject are minor.
Examples of "invasiveness"
1)

A CT or Contrast MRI scan performed for research purposes (CT is considered invasive forresearch purposes even when conducted without using a contrast medium because it involves radiation
exposure). However, various imaging tests (CT, MRI, etc.) performed for medical treatment purposes
are not categorized as "invasive." For example, if the objective is to investigate the diagnostic
performance of CT, it is considered "invasive"; however, using only the results of CT performed indaily clinical practice for disease monitoring is not regarded as "invasive."2)

Nuclear medicine tests using radioisotopes conducted for research purposes. (Note 2)

3)

Tissues collected through puncture or incision solely for research purposes.

4)

The use of unapproved drugs, unapproved medical devices, etc. for research purposes is

considered invasive, as is their use within approved or indicated scope. In this case, research involving
drugs and medical devices that are either unapproved or used off-label falls under the category of"specified clinical research" and is subject to compliance with the "Clinical Trials Act." Moreover,even if drugs, medical devices, etc., are already approved or within the approved scope, efforts must
be made to comply with the "Clinical Trials Act," when assessing their efficacy or safety, rather thansolely relying on this guideline. Additionally, research on drugs, medical devices, etc. funded bycompanies, etc. falls under "specified clinical research" and is required to comply with the "Clinical
Trials Act," regardless of the approval status of the target drug, medical device, etc., or its approved
scope of application.
*Reference: "Regulatory Classification in Medical Care."
The administration of unapproved drugs, off-label use of approved drugs, or use of unapproved
medical devices for providing the best medical care (for medical treatment), such as life-saving
interventions, falls within the scope of medical care and is not governed by this guideline.
"Invasiveness" in this guideline refers only to medical procedures performed for research purposes.
Note 1 Refers to actions conducted solely for “research purposes”; their use in medical care, suchas life-saving interventions, is not regarded as "invasive."
4Note 2 Uninsured sentinel navigation surgery conducted for research purposes is also included
within this guideline.
2.

Definition of "minimal invasiveness"
Socially acceptable minimal injuries and burdens to the study subjects, which are not considered"invasive."
Examples of "minimal invasiveness"
1)

Collecting a small amount of blood solely for research purposes. However, note that evensuch a small amount may be considered invasive depending on age and physical constitution.
2)

Plain X-ray performed for research purposes.

3)

MRI without contrast. The imaging range should be minimized. However, in children andpregnant women, imaging tests themselves may be invasive, and therefore, require careful andappropriate judgment.
4)

Cases where procedures such as puncture, incision, or blood collection performed forresearch purposes, in addition to those performed for routine clinical care, result in minimal additionof physical or mental injury or burden to the subject relative to those performed for routine nonresearch purposes.
3.

"Procedures, etc. for informed consent (IC) in invasive or minimally invasive studies"
The IC of the subject or their legally acceptable representative is essential for invasive or minimallyinvasive studies. Additionally, if the study involves "invasive procedures (excluding minimallyinvasive)" and includes "medical practice beyond routine clinical care," appropriate insurance policies
or other necessary measures must be adopted beforehand to compensate for health injuries incurredby study subjects in relation to the study. For detailed guidelines on the compensation framework,
refer to the "Guidelines for Compensation for Health Damage of Subjects" published by the Japan
Pharmaceutical Industry Legal Affairs Association (IHOKEN).
4.

What is "medical practice beyond routine clinical care"?
The term refers to the use of drugs (including in vitro diagnostics) or medical devices not approved

based on the PMD Act (hereafter referred to as "unapproved drugs or unapproved medical devices"),the use of approved drugs or medical devices beyond the scope of approval (such as dosage andadministration, directions for use, indications, and performance), or the implementation of new
medical technologies that do not align with the specified clinical study regulations outlined in the"Clinical Trials Act" (hereafter referred to as a "study using unapproved drugs/medical devices"). If atreatment is considered medically appropriate and routinely administered, such as when it is covered5

by health insurance, it may not be categorized as "medical practice beyond routine clinical care.""Intervention" refers to "medical practice beyond routine clinical care conducted for research
purposes." This does not mean that all medical activities beyond routine clinical care are immediately
deemed "interventions." "Medical practice" encompasses procedures targeting not only patients but
also healthy people and those not intended for disease prevention, diagnosis, or treatment; for example,
aesthetic plastic or breast augmentation surgery, which is intended to affect the structural function of
the human body. Even when not involving medical practice beyond routine clinical care, a study is
considered "interventional" if it controls the presence, absence, or degree of factors affecting events
related to human health, such as through random or non-random allocation based on the study protocol.
If these studies are conducted not as research but as clinical care, providing the highest standard of
medical care per the rules of each institution is necessary, as outlined in the "Standards for Medical
Care Using Unapproved New Drugs, etc. Based on the Provisions of Article 9-23, Paragraph 1, Item
8 (b) of the Enforcement Regulations of the Medical Care Act (HPB Notification No. 0610-24)."*Even if the drug is regarded as off-label, it may not be categorized as "medical practice beyondroutine clinical care" if it is medically appropriate and widely used, such as its administration tochildren or for postoperative infection prophylaxis, both of which are already covered by medical
insurance. However, when these practices are conducted as research, they are classified as "specified
clinical research" per the "Clinical Trials Act."
III.

Interventional Study (Categories C, D1, and D2 in Figure: Classification of the presentations

submitted to the Japanese Society for Oral and Maxillofacial Surgery)1.

Definition of "intervention"
An act of controlling the presence, absence, or degree of factors affecting various events related tohuman health, including actions aimed at maintaining and promoting health, as well as medications,tests, etc. for the prevention, diagnosis, or treatment of injuries or diseases in medical care (comprising
medical practice beyond routine clinical care conducted for research purposes). Among these, research
involving the use of a drug or medical device that is either not approved or used beyond its approved
scope falls under the category of "specified clinical research" and must adhere to the regulations
outlined in the "Clinical Trials Act." Additionally, studies aimed at evaluating the efficacy or safety ofdrugs, medical devices, etc., whether they are approved or fall within the approved scope, are obligatedto make efforts to comply with the "Clinical Trials Act." Research aimed at evaluating the efficacy andsafety of a drug or medical device, etc., funded by a company, falls under the category of "specified
clinical study" and must comply with the "Clinical Trials Act," regardless of the drug's approval status
or the scope of its application.

6

2.

Examples of interventional studies

1)

Random or non-random allocation (including blinding) for the prevention, diagnosis, andtreatment of injuries/diseases, and other factors affecting the health of study subjects, constitutes anaction aimed at controlling factors affecting events related to human health for research purposes,
and falls under the category of "intervention." Allocation encompasses both scenarios: dividing the
population of study subjects into multiple groups and conducting a single group (single-arm) study
without a control group, in which specific treatment methods, preventive measures, and other factors
affecting the health of the study subjects are restricted.
Specific examples of interventional studies include randomized controlled trials, which are conductedto compare the effects of medical activities, even within the approved scope, by assigning the subjects
to two or more groups. In this case, the presence or absence of blinding is not considered.
Interventional studies also include prospective, single-arm studies in which allocations are madeintentionally and treatment methods are restricted.
2)

A study including medical practice beyond routine clinical care performed for research

purposes.
Specific examples of an interventional study: The off-label use of anti-cancer drugs, including
molecular target drugs, for research purposes in subjects with surgically unresectable malignant
tumors for which no standard therapy has been established.
→Off-label use of drugs is subject to mandatory compliance with the "Clinical Trials Act."
However, a report on a case for which life-saving measures are unavoidable under the patient's IC may
not always be regarded as an interventional study but as an observational study.
3.

Supplementary information/Precautions

1)

An unapproved endoscopic surgery performed for research purposes necessitates a review

by the Ethical Review Board or an equivalent advisory committee of each institution, along with thepermission of the institutional head based on this review, per the "medical guidelines." Additionally,
written IC from the study subject or their legally acceptable representative is essential. However, if
the endoscopic procedure includes the use of unapproved or off-label drugs/medical devices and theircontribution to the success or conduct of the study surgery/procedure is significant, compliance withthe "Clinical Trials Act" becomes obligatory. If a surgery is intended solely for medical care purposes
because of the patient's condition, etc., it will not be regarded as research. However, it must be
performed following the implementation regulations for off-label medical care, high-difficulty
medical care, etc., as stipulated by each institution following the "Standards for Medical Care Using
7

Unapproved New Drugs, etc. Based on the Provisions of Article 9-23, Paragraph 1, Item 8 (b) of the
Enforcement Regulations of the Medical Care Act (HPB Notification No. 0610-24)."2)"Intervention" includes an action that restricts the selection of alternative treatment methods

because it is continued for a certain period for the research purpose, even if it is a treatment method
used in medical care. By contrast, if medical information, such as outcomes and prognosis, isprospectively collected from study subjects with a specific disease without controlling medications
and tests, the study will be considered as a study without "intervention" (observational study).
3)"Intervention" does not always involve "invasiveness." For example, when a new method,such as smoking cessation/abstinence guidance or diet therapy, is implemented to prospectively
evaluate the difference from the conventional method, the procedure falls under "intervention" because
the effects of care with different methods are compared or verified, but the procedure does not involve“invasion.”
4.

Ethical review and IC for interventional studies
Regardless of whether the research is conducted at a single center or multiple centers, the principal

investigator at all participating institutions must ensure that the study is reviewed by the Ethical
Review Board, the Institutional Review Board (IRB), or an equivalent committee, and permission of
the institutional head is obtained based on this review. Additionally, the IC of study subjects or theirlegally acceptable representative is essential. Moreover, interventional studies must be registered in
the public database established by jRCT and UMIN before the study is conducted. However, in cases
where a study involves intervention but not invasiveness, obtaining IC in writing may not always benecessary. If written IC is not obtained, oral consent must be obtained for the matters to be explained
per the provisions of the Life and Medical Guidelines. Furthermore, records must be maintained
detailing the method and content of the explanation provided and the consent received.
A study that does not correspond to an interventional study (= observational study).
A study using existing samples/information: A study that uses (1) samples/information that alreadyexisted before the preparation of the study protocol or (2) samples/information obtained after the
preparation of the study protocol, which were not intended for use in the specified study protocol at
the time of acquisition. A study employing these methods is classified as an observational study, not
an interventional study. If consent (IC or appropriate consent) is necessary in principle but obtaining
it is difficult (IC or appropriate consent), then opt-out may be considered acceptable.
<In the case of a study using samples>
If obtaining written IC is not deemed necessary, then oral IC must be obtained. However, IC is not
required if any of the following applies:8[1]Only a sample is used, rendering identification of a specific individual impossible;[2]

Pseudonymized personal information (limited to information that has already been prepared)

is used in the study;[3]

Obtaining IC is difficult and pseudonymized personal information is used in the study; or[4]Information related to personal information is used in the study.

If conditions (1) to (4) mentioned above do not apply, but obtaining IC or appropriate consent proves
to be challenging, then opt-out may be used instead.
<In the case of a study not using samples>
If the information used in the study is (1) pseudonymized (limited to already prepared information);or (2) pseudonymized personal information or related to personal information, then obtaining IC may
not always be necessary. However, if the information does not fall under (1) or (2), the use of opt-out
can substitute IC.
<In the case where the study is conducted by obtaining new samples/information>aInvasive study

Written IC must be obtained.
b

In the case of a non-invasive observational study using samples

Obtaining IC in writing may not always be necessary. However, if written IC is not obtained, oral IC
must be obtained for the matters to be explained per the provisions of the Life and Medical Guidelines.
Furthermore, records must be maintained detailing the method and content of the explanation provided
and the consent received.
c

In the case of a non-invasive observational study that does not use samples(ⅰ)

If sensitive personal information is acquired

Obtaining IC may not always be necessary. However, if not, appropriate consent as per the Personal
Information Protection Law for study subjects, etc. must be obtained in principle. If obtaining IC
and appropriate consent from study subjects, etc. proves challenging and if the rights and benefitsof the study subjects are not at risk of undue infringement, an opt-out approach may be used insteadof IC.
(ⅱ)

If sensitive personal information is not acquired

Obtaining IC in writing may not always be necessary. However, if IC is not acquired, then opt-out
must be exercised.
<If the study involves obtaining new samples/information through a study cooperation institution>
Researchers and other involved parties are responsible for following the aforementioned procedures.
Additionally, the study cooperation institution must confirm that the procedures have been9

implemented.

IV.

Observational Study (excluding case reports) (Categories B1 and B2 in Figure:Classification of the presentations submitted to the Japanese Society for Oral and Maxillofacial
Surgery)
1.

Definition of "observational study" (Note 3)
A retrospective study other than case reports, defined later, falls under the category of "observational

study." Among prospective studies, those that do not affect routine medical practice or medical
judgment (= do not include intervention) fall under the category of "observational study." Anobservational study includes additional blood sampling and imaging conducted for research purposes.
Note 3The statement "An observational study includes additional blood sampling and imaging

conducted for research purposes" may be debatable. The term "observational study" is not mentioned
in the Ethical Guidelines. However, the concept in these guidelines aligns with that of a conventional
observational study. Even if the study is prospective, if the results of blood sampling and imaging tests
are not used for medical care, it constitutes an observational study. Case reports intended for purposes
other than research are also broadly categorized as observational studies. The Japanese Society of Oraland Maxillofacial Surgeons distinguishes between observational studies and case reports because of
potential misinterpretations.
2.

Specific examples of an observational study
An observational study comprehensively analyzes genetic polymorphisms in cancer study subjects

using stored blood and retrospectively analyzes the relationship between sensitivity to anti-cancer
drugs and life prognosis. However, an interventional study reflects the analysis results in the selectionof anti-cancer drugs and examines their efficacy.
3.

What is "Opt-out"?
It refers to a process where information about a study is directly notified to the study subjects or ismade publicly available on a bulletin board or website of the institution. This provides an opportunity
for the study subjects to refuse participation in the study. Additionally, explicitly displaying the contact
point (contact information) is necessary for accepting the indication of refusal intention.
4.

Ethical review and IC for an observational study

1)

An observational study using existing samples and information[1]

An observational study using existing samples and information10

If obtaining consent (IC or appropriate consent) proves practically impossible in a study utilizing
solely information acquired in routine medical care or other studies, the opt-out approach may
substitute consent (IC or appropriate consent), ensuring an opportunity for refusal.
[2]

A multicenter observational study (using existing samples and information)

When serving as a collaborating research institution in an observational study designed as amulticenter investigation, the principal investigators from all participating institutions mustcollectively undergo a review by the Ethical Review Board overseeing the lead researcher's institution.
By contrast, institutions only providing samples/information without conducting research (providing
existing information alone does not automatically confer co-authorship) are not required to undergo
an Ethical Review Board assessment as a research entity. However, outlining that the research
institution (acting as the research representative institution) solely provides all existing information in
the protocol as part of the study implementation system is essential. Additionally, it must undergo
review by the Ethical Review Board together with the opt-out sample. The provision of informationmust be approved by the institutional head (#).
#: The principal investigator of the study site needs to confirm the name and address of the institution
providing the samples/information, as well as the name of the institution's head. Additionally, theyshould ascertain the background of sample/information collection (e.g., information collected during
medical care), the status of IC and opt-out, etc. for study use and to ensure the traceability of thesamples/information.
2)

An observational study involving the acquisition of new samples and information[1]

An observational study involving the acquisition of new information

Even in the case of an observational study, if invasive or minimally invasive procedures such asadditional CT scans, X-ray imaging, and blood collection are introduced for information
analysis/collection, IC becomes mandatory. However, for tests and questionnaires deemed noninvasive, such as body-surface ultrasound, explicit IC may not be necessary. Instead, compliance withappropriate consent procedures outlined in the Act on the Protection of Personal Information, etc. isrequired. If sensitive personal information is not gathered, the consent of study subjects may besubstituted by providing an opportunity for refusal using the opt-out approach.
[2]

An observational study involving the acquisition of new samples

Even in the case of an observational study, if invasive or minimally invasive tests such as additional
biopsy or blood collection are added, written IC is required. However, if samples collected for research
purposes include urine, stool, sputum, or spontaneously excreted secretions such as saliva and sweat,
they are considered non-invasive, and oral IC is acceptable, although opt-out is not permissible.
11

In multicenter studies, all participating sites in principle undergo collective review by the ethics
review committee of the research representative.
However, institutions outside the study sites, which obtain new samples/information from thesubjects for the study (excluding acquisition of samples accompanied by invasion [minimal invasion])based on the protocol and provide them solely to the study sites are designated as study cooperation
institutions and are exempt from review requirements for the study site. Even in this case, researchers
must obtain IC for study subjects at the study institution. Therefore, it is necessary for researchers tovisit the study cooperation institutions or use an electronic method to obtain IC. In addition, study
cooperation institutions must confirm that the IC has been obtained appropriately.

V.

Case Report (Category A in Figure: Classification of the presentations submitted to theJapanese Society for Oral and Maxillofacial Surgery)
1. Definition of a case report
The Japanese Society of Oral and Maxillofacial Surgeons defines a case report in medical researchas one involving ≤9 cases (Note 4). Study reports of ≥10 cases are classified as observational studies.
However, regardless of case numbers, reports with strong research aspects, such as evaluating theeffectiveness and safety of medical care, are treated as research. For example, descriptions such as"We experienced a case of ○○," "We encountered a case in which ○○ was effective," and " ○○ wasconsidered to be safe" fall under the category of case reports. Conversely, descriptions such as "We
examined the efficacy" and "The safety was examined," suggest a strong research aspect, warranting
attention to such expressions.
Note 4

Based on the opinion of biostatisticians, a case report was defined as one involving ≤9 cases.

Typically, multivariate analysis becomes feasible with more than 10 cases. Therefore, case reports
with ≥10 cases are included in observational studies.
2.

Specific examples of a case report
A report detailing 8 cases of patients with single liver cancer treated with proton beam or heavy ion

radiotherapy falls under a case report. However, if advanced medical care is administered, obtaining
approval from the Ethical Review Board as clinical research is necessary.
3. Precautions
Notably, the following example cannot be regarded as a case report but is an observational study.
Example: "RFA therapy was performed in 8 patients with hepatocellular carcinoma using a new12

puncture needle as clinical care but not for research purposes. We retrospectively compared these 8
patients with those treated with RFA therapy using the former type of puncture needle." This
constitutes an observational study.
4. Ethical review of case reports and ICAttention must be paid to ensure that study subjects remain unidentified in line with privacy
protection and compliance with the Personal Information Protection Law and the "Guidance forAppropriate Handling of Personal Information by Medical and Nursing Care Service Operators"(MHLW, applied on May 30, 2017, which underwent partially revisions in October 2020 and March
2022: https://www.mhlw.go.jp/content/000909511.pdf). Review by the Ethical Review Board orequivalent committee is not necessary. In principle, obtaining the subject's consent is necessary;
however, if obtaining consent proves challenging because of factors such as relocation and death, an
exemption from consent may be granted. In any case, precautions must be taken to prevent theidentification of individuals.
Even if a case report includes "medical practice beyond routine clinical care," if such practice was
performed solely as clinical care, it will still be regarded as a case report. However, the use ofunapproved drugs and medical devices, as well as off-label use, should adhere to the implementation
regulations for unapproved medical care, high-level medical care, etc. established by each institution
and per the "Standards for Medical Care Using Unapproved New Drugs, etc. Based on the Provisionsof Article 9-23, Paragraph 1, Item 8 (b) of the Enforcement Regulations of the Medical Care Act (HPB
Notification No. 0610-24)."

VI.

Genetic Analysis Research (Categories B2 and C in Figure: Classification of thepresentations submitted to the Japanese Society for Oral and Maxillofacial Surgery)
When analyzing the whole genome sequence of an individual or examining germline mutation or
polymorphism, certain information may lack sufficient accuracy or reliability for evaluating the healthstatus, etc. of the study subject. Therefore, explaining all genetic information comprehensively
becomes challenging, necessitating the consideration of limiting the explanation to parts that can bereliably used for evaluation of the health status, etc. of the study subject. This ensures that the study's
integrity remains unaffected while ensuring a proper understanding of the information provided.

VII.

A Study Not Requiring Ethical Review, Permission of the Institutional Head, or Study

Subjects' IC (Category A in Figure: Classification of the presentations submitted to the JapaneseSociety for Oral and Maxillofacial Surgery)13

A study falling under any of the following categories:
1. A study conducted following the requirements of applicable laws and regulations.
"Cancer Registration Project," "Survey on the Trend of Infectious Diseases," and "National Healthand Nutrition Survey" conducted at either the prefectural or national level.
2. A study included in the scope of application of standards stipulated by laws and regulations(excluding the Clinical Trials Act and the Act on the Safety of Regenerative Medicine, etc.).
3.

A study that uses only the following materials/information:

1)

A study using generally available specimens and information (e.g., data and guidelines

widely published as papers and databases) that hold established academic values and are widely
employed for research. A study using various cultured cells (including human ES cells, human iPS
cells, and human tissue stem cells) widely used for research. However, studies involving the clinicalapplication of human iPS cells, human ES cells, and human tissue stem cells to humans need to comply
with the "Act on Securing Safety of Regenerative Medicine, etc. (Act No. 85, 2013)."
2)

A study utilizing existing information that does not fall under the category of personal

information (personal information, pseudonymized personal information, anonymously processed
information, information related to personal information, and information equivalent to suchinformation on a deceased person) or anonymously processed information that has already been
prepared.
(Addition) "Already" refers to the time point when the study is conducted. This does not apply to
information processed for future research.
4.

A report, etc.* not aimed at acquiring knowledge for maintenance/promotion of humanhealth, recovery from illness/improvement in quality of life by understanding the causes/pathology ofillness/injury, improvement in prevention/diagnosis/treatment methods of illness/injury, andverification of efficacy/safety.
*(Examples): [1] Mere introduction of treatment methods or introduction of education and training
methods; [2] Introduction of an institution's medical system and efforts to improve the consultation
rate.
5.

Studies conducted overseas (excluding those in which samples and information are collected

in Japan) However, complying with the regulations of the country where the study was conducted isnecessary.
6.

A study merely analyzing microorganisms isolated from the human body, such as bacteria,
14fungi, and viruses, and does not include events related to human health.

VIII.

Algorithm for Determining Study TypeThe figure shows algorithms for "invasive" studies, "interventional studies," "observational
studies," and "case reports" in life science/medical research. Note that the following do not require
review by the Ethical Review Board or its equivalent committee, permission of the institutional head,and consent (IC) from research/study subjects:[1]

A study conducted per the provisions of laws and regulations (such as the local government's

cancer registration project);[2]

A study using only published articles, books, guidelines, and information published on

websites, as well as cultured cells widely used for research; and[3]Life science/medical research employing only existing information that does not correspondto personal information.
FigureFlowchart for judging the category of the presentations submitted to the Japanese Society

for Oral and Maxillofacial Surgery (see the attachment)
FigureClassification of the presentations submitted to the Japanese Society for Oral andMaxillofacial Surgery (see attachment)

IX.

Compensation for Medical Research (Clinical Research Insurance)

Type of Study and Compensation
An "invasive" study with medical practice beyond routine clinical care
→ Take measures for compensation
An "invasive" study within the scope of routine clinical care
→ Explain the presence or absence of compensation to the subjects
A non-"invasive" or a "minimally invasive" study→ No regulations"Specific Recommendations of the MHLW regarding Compensation"
1.

Compensation entails providing relief to eligible subjects to safeguard their interests, evenin the absence of liability for negligence, and obtaining compensation insurance is advisable. However,15

participating in the insurance is not mandatory because institutions may be able to cover costs
internally without insurance.
2.

Including compensation provisions equivalent to those outlined in the "Guideline forCompensation by the IHOKEN: https://www.ihoken.or.jp/htdocs/index.php?page_id=137" which has
been already used in clinical trials.
3.

Compensation may extend beyond monetary compensation and could also manifest in theform of medical benefits offered by each institution.
4.

Compensation insurance does not cover subjects on drugs such as anti-cancer drugs(including molecular target drugs) and immunosuppressants, which are known to cause serious
adverse reactions frequently. Practical supplementation can be achieved through measures such as
medical benefits. Explaining the actual policy and financial matters of compensation to subjects inwriting and obtaining their IC in advance is necessary.

X.

A Study Not Involving Human Subjects
Studies not involving human subjects can be divided into two main groups: those related to animal

experiments and gene recombination experiments, and those related to administration and systems,
such as medical administration and system, work style reform, incentives for dentists, inter-facility
collaboration, medical ethics, medical safety, education, disaster countermeasures, and research design
development.
Animal experiments and genetic recombination experiments should be conducted at each site withappropriate protocols, referencing the "Commitment on Bioethics in Life Science" (MEXT website
http://www.lifescience.mext.go.jp/ bioethics/seimei_rinri.html), "Commitment on Safety in Life
Science" (MEXT website http://www.lifescience.mext.go.jp/bioethics/anzen.html), and "Basic
Guidelines for Conduct of Animal Experiments in Research Institutions" (MEXT website
http://www.mext.go.jp/b_menu/hakusho/nc/06060904.htm).

Forstudies

relatedtomedicaladministration and systems, activities such as interviews and questionnaire surveys with study subjects
are considered to fall under observational studies or studies involving invasiveness/intervention.
Therefore, ethical procedures at institutions and related academic societies are required.

This guideline was enforced starting March 1, 2021.
However, a trial was conducted for the presentations submitted to the 66th Congress (scheduled for
November 2021). Full-scale implementation for the proposed presentations to the 67th Congress(scheduled for November 2022).
This guideline was enforced starting April 22, 2024.
16

However, a trial will be conducted for the presentations submitted to the 69th Congress (scheduled
for November 2024). Full-scale implementation for the proposed presentations to the 70th Congress(scheduled for November 2025).

17

Flowchart for judging the category of the presentations submitted to the Japanese Society
for Oral and Maxillofacial Surgery

Individual research/study should be confirmed by each researcher per the"Ethical Guidelines for Life Science and Medical Research Involving
Human Subjects" (Notes 6, 7).

Does your presentation/paper meet any of the following criteria?
 It is a research (study) covered by the Act on the Safety of Regenerative Medicine (however, if it is solely a basic study using human ES cells, human iPS cells, or human tissue stem
cells, proceed to NO).
 It is a study on human gene therapy.

It meets any of the following criteria:






It is a summarized case report (Note 1) of ≤9 patients without a research aspect.
It is a report not aimed at acquiring knowledge for the maintenance/promotion of human health, recovery
from illness/improvement in quality of life by understanding the causes/pathology of illness/injury,
improvement in prevention/diagnosis/treatment methods of illness/injury, and verification of efficacy/safety*.
*(Examples): [1] mere introduction of treatment methods, introduction of education/training methods, [2]introduction of the institution's medical system and efforts to improve consultation rate.
It is a study using only papers, published databases, and guidelines..
It is a study using generally available specimens and information that hold established academic values
and are widely employed for research.









It is a study using existing information that does not fall under the category of personal information (personal
information, pseudonymized personal information (Note 2), anonymously processed information (Note 2), information
related to personal information (Note 2), and information equivalent to such information on a deceased person).
It is a study using anonymously processed information that has already been prepared.
It is a study based on applicable laws and regulations (excluding the Clinical Trials Act and the Act on the Safety ofRegenerative Medicine, etc.).
It is a study merely analyzing microorganisms isolated from the human body, such as bacteria, fungi, and viruses anddoes not include events related to human health.
It is basic research using animal experiments and generally available cells (including iPS cells and tissue stem cells).
It is a study conducted overseas (excluding one in which samples and information are collected in Japan).
However, complying with the regulations of the country where the study was conducted is necessary.

It is a study that involves making the allocation, restricting medical practice (single-arm), or conducting tests andtreatment for research purposes, affecting treatment policy and prognosis of patients beyond routine clinical care.

It is a study that involves obtaining new samples and information
for research purposes.

It is invasive or minimally invasive.
(Proceed to YES for a study in whichbiological samples are obtained, even if it isnon-invasive.)

It is a study using
existing samples andinformation (Note 3).

▪ Questionnaire▪ Body-surface
US, ECG, etc.

▪ Invasive (e.g., CT, contrast-enhanced
MRI, PET, endoscopy, biopsy)▪ Minimally invasive (e.g., simple MRI, blood
sampling)▪ Non-invasive(e.g., collection of urine, stool, and otherexcreta)

ObservationalStudy
A study that does not require
ethical review.
Review and approval by the Ethical
Review Board is not required.
For case reports, etc., obtaining
consent to publish must adhere to the"Act on the Protection of Personal
Information" and "Guidance forAppropriate Handling of Personal
Information by Medical and Nursing
Care Service Operators." However, if
obtaining consent proves challenging
because of factors such as relocationand death, an exemption fromconsent may be granted.

 An observational study using
existing samples andinformation
 An observational study in which
only new information is
obtained and is not invasive.

 An observational study associatedwith invasiveness or minimal
invasiveness when new information
is obtained for research purposes.
 An observational study in which
new samples and information are
obtained for research purposes.
All the following requirements must be met:

All the following requirements must be
met: Permission of the institutional headbased on the review by the Ethical
Review Board, IRB, or an equivalentcommittee.
 Opt-out (Note 4) is available.

 Permission of the institutional head basedon the review by the Ethical Review Board,
IRB, or an equivalent committee.
 Written consent (IC) from the subjects ortheir legally acceptable representatives.
* If the study is non-invasive, oral consent (IC) is acceptable.

It is a study evaluating the efficacy and safety of drugs, medical devices,
etc.

Evaluation of healthfood, in vitro
diagnostics, medical
procedures, etc.

It is a study that falls
under the Act on the
Safety ofRegenerative
Medicine, etc. It is a
study on human genetherapy.
It is a study obligated tocomply with the "Act on
the Safety ofRegenerative Medicine,etc." or "Guideline forClinical Studies of Gene
Therapy, etc."

It meets any of the following criteria:▪ Use of unapproved or off-label drugs/medical devices, etc.
▪ Funded by a company.

InterventionalStudy
An interventional study to which
the "Clinical Trials Act" does not apply.
All the following requirements must be met: Permission of the institutional headbased on the review by the Ethical
Review Board, IRB, or an equivalentcommittee.
 Written consent from the study subjects
or their legally acceptable
representatives.
 Registration to public database.

A clinical study other thana specified clinical research
It is a study that is obligated to makeefforts to comply with the Clinical
Trials Act. (Note 5)

Specific clinical research
It is subject to mandatorycompliance with the "Clinical Trials
Act." (Note 5)* If the study is non-invasive, oral consent is
acceptable.

* When acquiring new information, obtaining appropriate
consent per the principles of the Personal Information
Protection Law, etc. is generally required.

*This guideline is prepared based on the
ethical guidelines of the Japan Digestive
Disease Week.

Note 1 See "V. Case Report" in the main text.
Note 2 See "VII. A Study Not Requiring Ethical Review,
Permission of the Institutional Head, or Study Subjects'
IC" in the main text.
Note 3 See "IV. Observational Study" in the main text.
Note 4 See "IV. Observational Study" in the main text.
Note 5 See "II. Invasive Study" in the main text.

Observational Study
Interventional Study
MHLW
approval isrequired.

Category Classification

A study that does not require
ethical review.

Classification of the presentations submitted to the Japanese Society
for Oral and Maxillofacial Surgery.
➢ A summarized case report (Note 1) of ≤9 patients without a research aspect.
➢ A report, etc.* not aimed at acquiring knowledge for maintenance/promotion of human health, recovery from illness/improvement in quality of life by understanding the causes/pathology ofillness/injury, improvement in prevention/diagnosis/treatment methods of illness/injury, and verification of efficacy/safety*(Examples): [1] mere introduction of treatment methods, introduction of education/training methods, [2] introduction of the institution's medical system and efforts to improve consultation rate.

➢ A study that uses only papers, published databases, and guidelines.
➢ A study using generally available specimens and information that hold established academic values and are widely employed for research.
➢ A study using existing information that does not fall under the category of personal information (personal information, pseudonymized personal information (Note 2),
anonymously processed information (Note 2), information related to personal information (Note 2), and information equivalent to such information on a deceased
person).
➢ A study using anonymously processed information that has already been prepared.
➢ A study based on laws and regulations (excluding the Clinical Trials Act and the Act on the Safety of Regenerative Medicine, etc.).
➢ A study merely analyzing microorganisms isolated from the human body, such as bacteria, fungi, and viruses, and does not include events related to human health.
➢ Basic research using animal experiments and generally available cells (including iPS cells and tissue stem cells).
➢ Studies conducted overseas (excluding those in which samples and information are collected in Japan) However, complying with the regulations of the country
where the study was conducted is necessary.
➢ A study using existing samples and information (Note 3).
Prospective or retrospective status is irrelevant if the routine clinical practice is not impacted (judgment); for instance, the use of information from routine clinicalpractice and residual biological samples collected during medical practice.
➢ An observational study in which only new information is obtained for the study and is non-invasive.
ECG, body-surface US, and psychologically non-invasive questionnaires are included.

➢ An observational study associated with invasiveness or minimal invasiveness when new information is obtained for research purposes.
This includes studies in which X-rays, CT, etc. are conducted for research purposes without affecting routine medical practice (judgment).
➢ An observational study in which new samples and information are obtained for research purposes.
Some studies, while not affecting routine medical practice (judgment), may involve additional procedures such as CT, blood collection (including above-normal
quantities), and tissue collection, which can be categorized as invasive or minimally invasive. By contrast, other studies that include excreta collection are considered
non-invasive.

➢ An interventional study not subject to the "Clinical Trials Act."
Interventional studies using in vitro diagnostics and studies to evaluate medical procedures and surgical methods are included.

➢ A clinical study other than a specified clinical research (a study obligated to endeavor to comply with the Clinical Trials Act).
This includes interventional studies to evaluate the efficacy and safety of drugs and medical devices that have already been approved and for which no funding isprovided by related companies. (Note 5)➢ Specific clinical research (research obligation to comply with the "Clinical Trials Act").
This includes studies using unapproved or off-label drugs/medical devices, etc., or interventional studies funded by a company. (Note 5)➢ It is a study that falls under the Act on the Safety of Regenerative Medicine, etc.
➢ It is a study on human gene therapy.
* Comply with the "Act on the Safety of Regenerative Medicine, etc." or "Guideline for Clinical Studies of Gene Therapy, etc."

Note 1 See "V. Case Report" in the main text.
Note 2 See "VII. A Study Not Requiring*ForPermission
Notes 1 to
5, seethe maintext.
Ethical Review,of theInstitutional
Head,orStudy Subjects' IC" in the main text.
Note 3 See "IV. Observational Study" in the main text.
Note 5 See "II. Invasive Study" in the main text.