A Geriatric Assessment Intervention for Patients Aged 70 and Over Receiving Chemotherapy or Similar Agents for Advanced Cancer: Reducing Toxicity in Older Adults
Phase: NA
Conditions: Adult Solid Neoplasm, Toxicity, Lymphoma
Sponsor: Supriya Mohile

NCT02054741
Geriatric Assessment Intervention for Reducing 
Toxicity in Older Patients With Advanced Cancer
Last updated: 26-Sep-2016

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A Geriatric Assessment Intervention for Patients 
Aged 70 and Over Receiving Chemotherapy or Similar Agents for Advanced 
Cancer: 
Reducing Toxicity in Older Adults 
Protocol #: URCC13059 
URCC / University of Rochester NCORP Research Base 
NCT02054741 
Protocol submitted to NCI:  20-Jun-13 
Protocol submitted to NCI:  13-Sept-13 
NCI approved:  1-Oct-13 
Amendment submitted to NCI:  13-Dec-13 
Revised Amendment submitted to NCI:  23 Dec-13 
NCI approved:  15-Jan-14 
Amendment submitted to NCI:  3-Feb-14 
NCI approved: 10-Feb-14 
Amendment submitted to NCI:  17-March-14 
NCI approved: 19-March-14 
Amendment submitted to NCI: 13-Oct-14 
NCI approved 27-Oct-14 
Study Chairs: 
Co-Principal Investigators 
Supriya Mohile, MD, MS 
James P. Wilmot Cancer Institute 
URCC NCORP Research Base 
601 Elmwood Avenue, Box 704 
Rochester, NY 14642 
(585) 275-5513
William Dale, MD, PhD 
Arti Hurria, MD 
Research Base Co-Chairs 
Co-investigators 
Statistics Co-Chair 
Gary Morrow, PhD, MS 
Karen Mustian, PhD, MPH 
Gary Morrow, PhD, MS 
Karen Mustian, PhD, MPH 
Michelle Janelsins, PhD 
Marie Flannery PhD, RN AOCN 
Ronald Epstein, MD 
David Dougherty, MD 
Ekaterina (Katia) Noyes, PhD 
Mohamed Tejani, MD 
Arti Hurria, MD 
William Dale, MD, PhD 
Judith Hopkins, MD 
Rakesh Gaur, MD 
Charles Heckler, PhD 
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PROTOCOL CONTACT INFORMATION 
URCC NCORP Research Base: 
URCC NCORP Research Base  
Saunders Research Building 
265 Crittenden Blvd 
Box CU 420658Rochester, NY 14642 
phone:  585-275-5513 
fax:  585-461-5601 
website: 
http://extranet.urmc.rochester.edu/NCORP/ 
Principal Investigators: 
Supriya Mohile, MD, MS 
URCC NCORP Research Base 
William Dale, MD, PhD 
University of Chicago 
Arti Hurria, MD 
City of Hope Cancer Center 
Co-Investigators: 
Gary Morrow, PhD, MS 
Karen Mustian, PhD, MPH 
Marie Flannery, PhD, RN, AOCN 
        URCC NCORP Research Base 
Ronald Epstein, MD 
David Dougherty, MD 
Ekaterina (Katia) Noyes, PhD 
Mohamed Tejani, MD 
 University of Rochester 
Judith Hopkins, MD 
       SCCC NCORP Community Site 
Rakesh Gaur, MD 
       Kansas City NCORP Community Site 
Biostatistician 
Charles Heckler, PhD 
URCC NCORP Research Base 
Regulatory Contact: 
Cathy Lesniewski 
585-275-2282
cathleen_lesniewski@urmc.rochester.edu
Data Contact: 
Libby Nagalski
585-275-1364
elizabeth_nagalski@urmc.rochester.edu
Program Managers: 
Senior Program Manager: 
Nikesha J. Gilmore, PhD
585-275-1275
nikesha_gilmore@urmc.rochester.edu
Megan McKillip, MPH
585-275-1277
megan_mckillip@urmc.rochester.edu
Sandy Plumb
585-324-4553
sandy_plumb@urmc.rochester.edu
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TABLE OF CONTENTS 
STUDY SCHEMA AND SUMMARY ........................................................................................................ 3 
1. BACKGROUND INFORMATION ......................................................................................................... 4 
2. STUDY OBJECTIVES ............................................................................................................................. 9 
3. STUDY DESIGN .................................................................................................................................... 11 
4. PARTICIPANT ELIGIBILITY .............................................................................................................. 11 
5. IDENTIFICATION, RECRUITMENT, AND CONSENT PROCEDURES ......................................... 12 
6. REGISTRATION ................................................................................................................................... 14 
7. OUTCOMES........................................................................................................................................... 16 
8. MEASURES TO BE COLLECTED ....................................................................................................... 18 
9. NCORP PRACTICE SITE RANDOMIZATION ................................................................................... 21 
10. INTERVENTION OVERVIEW FOR PHYSICIANS .......................................................................... 22 
11. OUTLINE OF STUDY-SPECIFIC PROCEDURES............................................................................ 23 
12. REIMBURSEMENT ............................................................................................................................ 29 
13. ADVERSE EVENT REPORTING ....................................................................................................... 29 
14. CRITERIA FOR WITHDRAWAL ...................................................................................................... 31 
15. STATISTICAL PLAN .......................................................................................................................... 32 
16. DATA MANAGEMENT AND QUALITY ASSURANCE ................................................................. 34 
17. DATA COLLECTION AND MEASURES ......................................................................................... 36 
18. PARTICIPANT CONSENT AND PEER JUDGMENT ...................................................................... 36 
19. RECORD AND DATA RETENTION ................................................................................................. 36 
20. REFERENCES ..................................................................................................................................... 37 
APPENDIX A: SUMMARY OF MEASURES 
APPENDIX B: PARTICIPANT MEASURES 
APPENDIX C: CLINICAL RESEARCH ASSOCIATE MATERIALS 
APPENDIX D: PHYSICIAN MEASURES 
APPENDIX E: STUDY RELATED FORMS  
APPENDIX F: APPROVED  OTHER AGENTS WITH SIMILAR PREVALENCE OF TOXICITY 
     TO CHEMOTHERAPY 
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STUDY SCHEMA AND SUMMARY 
 
 
 
 
 
Adults age >70 who will start a new chemotherapy regimen or other regimen with similar toxicity 
prevalence (see section 4.2.1c)  for an advanced solid tumor malignancy in the University of Rochester 
Cancer Center NCI Community Oncology Research Program (URCC NCORP) Research Base network 
will be eligible.  Chemotherapy will be defined as cytotoxic drugs; in addition, agents (e.g., monoclonal 
antibodies and targeted agents) that have a prevalence of grade 3-5 toxicity in older patients similar to 
chemotherapy (>50%) will be allowed.  Oncology physicians who practice at sites within the URCC 
NCORP Research Base network are participants in the study and will be enrolled.  Their eligible patients 
will then undergo the informed consent process; those patients who agree to participate in this study will 
undergo a clinical assessment consisting of demographic characteristics and geriatric assessment (GA).  
All baseline assessments will be performed prior to initiation of the new treatment regimen.   
NCORP practice sites with IRB approval of the protocol will be randomized to receipt of GA plus GA-
driven recommendations (Arm 1) or usual care (Arm 2).  A NCORP practice site will be defined as any 
practice location within an overarching NCORP designation where oncology physicians and study staff 
work independently (e.g., do not cross over into another site).  In Arm 1, oncology physicians or their 
designees will be provided with GA summary plus targeted recommendations (i.e., GA-driven 
recommendations). GA-driven recommendations and the uptake of these recommendations along with the 
influence of the GA on decisions will be collected.  In Arm 2, participants will complete the GA; but no 
GA summary or GA-driven recommendations will be provided to the oncology teams except for 
information regarding clinically significant cognitive impairment and/or depression. In both arms, 
participants will subsequently receive a treatment plan as prescribed by the treating oncology physician.  
Drugs and doses (throughout the entire course) will be recorded, as well as supportive care medications.  
NCI clinician-rated and patient-reported CTCAE grade 2-5 toxicities will be captured.  In addition, dose 
delays, dose reductions, discontinuation of treatment, hospitalizations, and survival status will be 
captured, as well as the relationship of these events to toxicity.  A brief follow-up GA will be collected at 
4-6 weeks, 3 months, and 6 months after baseline registration. Survival will be captured for 1 year after
study entry.
A total of 700 participants will be enrolled in this study. The acronym for this study is GAP70+, which 
stands for Geriatric Assessment for Patients 70+: A Bridge to Reduce Toxicities. 
Cluster Randomized Trial 
Patients 
Age ≥ 70 
Advanced solid 
tumor malignancy 
To receive a new 
chemotherapy 
regimen or other 
regimen with 
similar prevalence 
of toxicity 
Physicians 
Chemotherapy or other agents 
with similar prevalence of 
toxicity 
(NCI CTCAE version 4.0)  
Arm 1 
Physician provided 
with GA summary 
and GA-driven 
recommendations for 
each enrolled 
participant prior to 
starting 
chemotherapy/agents 
with similar 
prevalence of toxicity 
Arm 2 
Usual Care 
R
A
N
D
O
M
I
Z
E 
S
I
T
E
S 
OUTCOMES 
 Grade 3-5
TOXICITY
 Survival
 Functional and
physical
performance
Oncology Decision Making 
- Chemotherapy or other
agents with similar
prevalence of toxicity
(Drugs, Doses, Schedule) 
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1. BACKGROUND INFORMATION
1.1. Intervention to be Studied 
The URCC NCORP Research Base will conduct a cluster randomized study evaluating whether 
providing a GA summary with targeted recommendations (i.e., GA-driven recommendations) can lower 
toxicity in older adults receiving chemotherapy or other agents (e.g., monoclonal antibodies, targeted 
agents) with similar toxicity prevalence for advanced solid tumor malignancies.  Clinical outcomes will 
be captured including toxicity (both clinician and patient-reported), other adverse outcomes (e.g., 
hospitalizations, mortality), and changes in functional and physical performance. 
1.2. Background and Significance  
Although cancer is a disease of aging, older patients are underrepresented in clinical trials.1,2  Balancing 
the benefits against the risks of chemotherapy in the older patient population is challenging because of the 
dearth of evidence-based data to guide these decisions.3,4  Furthermore, older patients who are treated 
with chemotherapy are at high risk for adverse outcomes including serious chemotherapy toxicity and 
functional and physical consequences.5-7 In addition, older patients have been found to be more 
susceptible to toxicity from other types of treatment (e.g., monoclonal antibodies and targeted agents) and 
some of these newer agents have similar prevalence of toxicity in older patients to chemotherapy.117-120  
For example, limited evidence exists to guide risks and benefits of the multi-kinase inhibitor, 
regorafenib, in the older adult. Participants in the Phase III CORRECT trial that led to approval of 
regorafenib in previously treated mCRC had a median age of 61. The small number of older 
participants (38 participants ≥ 75 years of a total n=503) in this study had a disproportionately higher 
risk of any ≥ grade 3 toxicities (66% for ≥ 75 years vs. 52% for < 65 years).120 
The American Society of Clinical Oncology (ASCO) has stated that to improve quality of care, oncology 
physicians and patients should carefully weigh the risks and benefits of cancer-directed therapy for 
patients with a low performance status, who are not eligible for a clinical trial, and for whom there is no 
strong evidence supporting the clinical value of treatment.8  These issues commonly affect older adults.  
The National Comprehensive Cancer Network (NCCN) guidelines advocate GA for older patients with 
cancer to identify health status issues that increase the risk of adverse outcomes.9-13  A GA evaluates 
comorbidity, functional status, physical performance, cognitive ability, psychological status, medications 
and social support with standardized tools that predict morbidity and mortality in community-dwelling 
older adults.14-16  Benefits of GA in community-dwelling older adults include prevention of geriatric 
syndromes, recognition of cognitive deficits, prevention of hospitalizations and nursing home admissions, 
and overall improvement of quality of life.15,17-19  Evidence derived from research on GA-driven 
recommendations in community-dwelling older adults without cancer could benefit older patients with 
cancer, but this evidence has not been widely adopted by oncologists.  The incorporation of GA as the 
standard of care in oncology has been slow due to lack of resources, difficulties with interpreting results, 
and difficulties with implementing targeted interventions.12,20,21 Innovative and pragmatic 
interdisciplinary approaches to reduce risk of treatment in older cancer patients are imperative.  This 
research supports the NIH commitment to trans-NIH strategic initiatives for the development of 
interdisciplinary research teams to address problems facing an aging nation.22  
The overarching goal of this proposal is to evaluate whether providing the oncology team with 
information from the GA plus GA-driven recommendations can improve outcomes in older adults with 
advanced cancer.  This proposal addresses the main objective of the U13 conference, “Geriatric Oncology 
Research to Improve Clinical Care,” which is to develop innovative mechanisms to improve the clinical 
care of older cancer patients within the next 10 years.3,4  The GA has great potential to identify areas of 
vulnerability and develop recommendations that could help improve outcomes (e.g., treatment toxicity) in 
older cancer patients.14,15,23  The PI, in collaboration with Cancer and Aging Research Group (CARG) 
investigators, has found that older cancer patients have a high prevalence of characteristics that are 
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associated with a greater risk of chemotherapy toxicity.24,25  This research is significant because:  1) a 
large and growing population of older cancer patients would benefit from the results; 2) GA information 
can identify risk factors for chemotherapy toxicity in older cancer patients; however, these questions are 
not routinely incorporated into the oncology clinical evaluation; and 3) a critical operational question 
exists: would provision of GA information along with GA-driven recommendations to the oncology 
treatment team improve outcomes in older patients with advanced cancer?  Successful completion of the 
aims of this proposal will provide an innovative, pragmatic approach that could improve clinical care.   
1.3. Condition to be Studied 
A growing population of older patients is at 
high risk for adverse outcomes from cancer 
treatment.  Cancer is a disease of aging; 
approximately 60% of all cancers and 70% 
of cancer mortality occur in persons aged 
65 years and over.26  The number of cancer 
patients over the age of 65 is projected to 
significantly increase over the next 20 
years (see Figure 1).27  Aging is a highly 
individualized process, characterized by an 
increased prevalence of health status 
conditions that can affect decision making 
for cancer treatment, treatment tolerance, 
and ultimately outcomes.3,28,29   The PI has 
shown that older adults with cancer have a 
high prevalence of comorbidity, disability, 
and geriatric syndromes.24,25  The majority 
of older patients with cancer are treated 
based on extrapolations of evidence derived from clinical trials providing data on the safety and efficacy 
of treatment in younger adults or in older patients who are fit without other health status conditions.30  As 
a result, cancer treatment guidelines are often extrapolated from studies of younger, healthier patients.  
Patients with health status issues other than cancer are often excluded from oncology clinical trials, 
despite the fact that the majority of older adults have these issues at the time of cancer presentation.25,31  
Other health status issues can affect the ability to tolerate cancer therapy.5,32-34  
1.4. Geriatric Assessment (GA) 
GA can identify risk factors for adverse outcomes in older cancer patients.  Comprehensive GA includes a 
compilation of reliable, validated tools to assess geriatric domains such as comorbidity, functional status, 
physical performance, cognitive status, psychological status, nutritional status, medication review, and 
social support.15,35-55  GA can detect unsuspected conditions that may affect cancer treatment in more than 
50% of older patients.56  Repetto et al. demonstrated that GA added information to standard oncology 
performance measures such as the Karnofsky score, a one-item measure of function, which was validated 
in younger patients.  The GA has great potential to identify areas of vulnerability and interventions that 
could help improve outcomes (e.g., reducing treatment toxicity) in older cancer patients.14,15,23  Notably, 
the primary investigator (PI) of this study, Dr. Supriya Mohile, in collaboration with CARG investigators, 
has demonstrated that older cancer patients have a high prevalence of characteristics that are associated 
with a greater risk of chemotherapy toxicity, and the GA can help identify these risk factors.  Our 
research team has found the GA in this study was feasible in oncology clinics and trials.5,12,23  
1.5 Geriatric Assessment Components and Relevance to the Older Patients with Cancer.   
Currently, oncology physicians assess functional status by assigning a Karnofsky performance status 
score (KPS) or Eastern Cooperative Oncology Group (ECOG) performance status.57,58  These generic 
scales are applied to all adult cancer patients, regardless of age, and are used to estimate functional status 
Figure 1:  Increase in older patients with cancer 
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in order to determine a treatment course, assess eligibility for clinical trials, and predict treatment toxicity 
and survival.59,60  These tools may result in misleading decisions for the older patient, since clinical trials 
relying on these scales have largely excluded elderly patients.  A prospective study of 500 older adults 
with cancer demonstrated that KPS could not identify older adults at risk for chemotherapy toxicity, while 
a predictive model including GA questions could identify such individuals.5  The geriatrician’s evaluation 
provides valuable information not provided by KPS or ECOG performance scores;14,16,61,62 however, GA 
is not commonly taught in oncology training or utilized in oncology practice. A description of each GA 
domain and its relevance to the older patient with cancer is provided below. 
1.5.1. Functional Status and Physical Performance.  The need for functional assistance (measured 
by the ability to complete activities of daily living) is predictive of chemotherapy toxicity and 
survival.63-66  Physical performance measures objectively evaluate mobility and fall risk.43,53  Falls are 
common in older cancer patients and predictive of adverse outcomes.5,25,67 
1.5.2. Comorbidity and Polypharmacy.  Among patients with cancer, comorbidity is associated 
with poorer overall survival.68-72  Comorbidity impacts cancer treatment tolerance.73-76  Furthermore, 
these comorbid conditions may predispose patients to the risks of polypharmacy and drug 
interactions.77 
1.5.3.  Nutrition.   Poor nutritional status is associated with an increased need for functional 
assistance and poorer overall survival in the geriatric population.78  Unintentional weight loss during 
the six months prior to chemotherapy is associated with lower chemotherapy response rates and lower 
overall survival.79  
1.5.4.  Cognition.  A cognitive assessment is needed to determine if the patient has the decisional 
capacity to consent and adhere to supportive care medication instructions and understand the 
indications to seek attention. In the presence of cognitive impairment, the involvement of the patient’s 
family or caregiver is required to maintain safety.80-83 
1.5.5. Psychological State and Social Support. In a study of older adults with cancer, significant 
distress was identified in 41% of older adults, and poorer physical function correlated with higher 
distress.83  In both the geriatric and oncology literature, social isolation has been linked to an 
increased risk of mortality.84-86     
1.6 Gap in Knowledge 
A critical knowledge gap exists regarding which GA-driven recommendations have the greatest 
likelihood to improve outcomes of older cancer patients and how to implement these 
recommendations.14,23,87 Despite the fact that the majority of cancer patients are in the older age groups, 
most oncologists have received little training in the care of older patients.88 As a result, common problems 
facing an aging population of cancer patients may go unrecognized and have serious consequences.87  For 
example, Hurria et al. revealed that although 5% of patients screened positively for severe cognitive 
impairment on GA, these patients were still consented onto a therapeutic protocol.23  Thus, although GA 
predicts risk from chemotherapy toxicity, there is no evidence-based approach that demonstrates how to 
intervene to reduce risk from cancer treatment.  An algorithm incorporating the best available evidence 
would help close the critical gap in knowledge regarding how to interpret GA results and implement 
interventions for older patients with cancer.  The GA and GA-driven recommendations utilized in this 
proposal have been developed through preliminary work, extensive review of the evidence, and clinical 
expertise of the geriatric oncology physicians on the research team.  Our research team has found that the 
GA in this study was feasible in oncology clinics and trials.5,12,23  
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1.7.  Geriatric Assessment-Driven Recommendations and Relevance to Older Patients with Cancer 
Interventions guided by GA have positive effects on health outcomes including the prevention of 
disability, and the reduction in the risk of falls, unplanned hospitalizations, and nursing home admissions, 
which provides evidence supporting the use of a multidimensional approach for older patients with 
cancer.17-19  Several studies have shown that the implementation of GA and GA-driven recommendations 
into the clinical care of older patients with cancer is feasible.12,21,56,89  The ELCAPA (elderly cancer 
patient) study illustrated that providing GA information and GA-driven recommendations to oncology 
teams can influence treatment decisions, although outcomes from these changes were not measured in this 
study.89  This study showed that decisions for both chemotherapy and other regimens were affected by 
providing GA information to the oncology team.   Another pilot study showed that GA affected the 
oncology treatment plan.90  However, published randomized studies evaluating outcomes from GA and 
GA-driven recommendations in older cancer patients are scant.  In a study by McCorkle et al.,91 geriatric 
nurse practitioners conducted GA with cancer patients, and this led to a distinct survival advantage (67% 
in the intervention group compared with 40% in the control group).  In a study by Goodwin et al., breast 
cancer patients in the GA-driven recommendations group were significantly more likely to return to 
normal functioning than the controls.92  Different approaches for treatment selection and dosing for older 
and/or frail patients is supported by the literature and is incorporated into the framework as GA-driven 
recommendations (see Preliminary Data).  The FOCUS-2 trial found that chemotherapy for advanced 
colorectal cancer was safe and efficacious in the older and/or frail patient if started at a 20% dose 
reduction with escalation as tolerated.93  
1.8 Preliminary Data 
The investigative team is poised to build upon a considerable body of prior work. The research team has 
conducted studies that have demonstrated the high prevalence of health status issues that could influence 
cancer outcomes in older patients.24,25  They have developed a Geriatric Assessment tool for older persons 
with cancer.12 The feasibility of this tool has been studied in hundreds of cancer patients in multicenter 
clinical trials.5,12,23 They have collaborated on a prospective multicenter study to quantify the risks of 
chemotherapy among older adults with cancer.5  Dr. Mohile has collected pilot data from over 200 
patients from her referral-based geriatric oncology clinic which administers GA-driven 
recommendations.94  Drs. Dale and Epstein have experience in the study of decision-making in oncology. 
1.8.1. Prevalence of Health Status Issues in 
Older Patients with Cancer.  Using a 
nationally representative population-based 
database, Mohile and collaborators (Dale and 
Morrow) published two investigations that 
demonstrated that disability, comorbidity, 
and geriatric syndromes (including falls) are 
more common in cancer patients and that 
cancer was independently associated with 
having these conditions (Figure 2).24,25  In 
addition, Drs. Hurria and Mohile collected 
GA data from over 500 older cancer patients 
receiving chemotherapy at 7 institutions.5  
The assessment revealed a number of 
findings that would not have been detected 
on routine history and physical exam: 41% 
of patients needed assistance with instrumental activities of daily living despite a mean physician-
reported KPS of 85, 16% had recent falls, and 6% had gross cognitive impairment on the cognitive 
screening test. 
Figure 2:  Prevalence of Comorbidity, Disability, 
and Geriatric Syndromes 
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1.8.2. Developing a Geriatric Assessment for Older Adults with Cancer.12  The geriatric and 
oncology literature was reviewed to choose validated GA measures.  Selection criteria included 
reliability, validity, brevity, the ability to self-administer, and the ability to prognosticate risk for 
morbidity or mortality in an older patient.12  The final selection of measures was approved by the 
Cancer and Leukemia Group B (CALGB) Cancer in the Elderly and Quality of Life Committees.  The 
initial feasibility study of this tool was conducted in a multicenter study by Dr. Hurria and Dr. 
Mohile.  Forty patients (mean age 74, range 65 to 87) with cancer participated in the study.  The GA 
was feasible, as demonstrated by a mean time to completion of 27 minutes, 90% of participants were 
satisfied with the questionnaire length, and 78% were able to complete on their own.12  
1.8.3. Feasibility of Geriatric Assessment Tool in Oncology Clinical Trials.23  CALGB 360401 
evaluated the feasibility of incorporating the GA into oncology cooperative group trials for older 
adults who had signed consent for a cooperative group treatment trial.  Ninety-three patients enrolled 
in this study.  The median time to complete the assessment was 22 minutes, 88% of participants 
completed the participant portion without assistance, 88% were satisfied with the assessment length, 
and 95% said the assessment was easy to comprehend.  The GA for cancer patients met the protocol 
specified feasibility criteria for use in the cooperative group setting.  
1.8.4. Can the Geriatric Assessment Predict Chemotherapy Toxicity?5  The primary objective of 
this study was to determine if GA measures predicted grade 3-5 toxicity using the NCI Toxicity 
Index, Common Terminology Criteria for Adverse Events (CTCAE, V3.0).  This study’s eligibility 
was the same for the current proposed study:  an older patient was enrolled prior to the start of a new 
chemotherapy regimen.  Among the 500 enrollees, the mean age was 73 years (range 65-91).  The 
most common tumor types were lung (29%), GI (29%) and breast/gynecologic (22%) cancers; 61% 
had metastatic disease and 71% received 1st line chemotherapy.  Grade 3-5 toxicity occurred in 53% 
(50% grade 3, 12% grade 4, 2% grade 5). Risk factors for grade 3-5 toxicity included: 1) age ≥ 73, 2) 
cancer type (GI or GU), 3) standard dose, 4) poly-chemotherapy, 5) falls in last 6 months, 6) 
assistance with instrumental activities of daily living, and 7) decreased social activity.  In the 
published CARG study, 307 of 500 participants had advanced cancer and of these, 141 (46%) 
experienced grade 3, 4, or 5 toxicity within 3 months.5 Seventy percent of the toxicities were non-
hematologic (fatigue, nausea/vomiting, etc.). 
1.8.5. GA-driven interventions can influence oncology care and improve chemotherapy toxicity.  
Dr. Mohile directs a referral-based consultative geriatric oncology clinic which has collected pilot 
data on GA-driven interventions in over 200 participants.94  Mean age was 82.1 (65-95) and 75% had 
advanced disease.  GA revealed 68% with functional impairment, 70% had >3 significant 
comorbidities, 39% had poor nutrition,95 26% screened positive for depression,96 59% reported 
inadequate social support, 20% had an abnormal cognition screen,97 34% had recently fallen, and 
60% had poor physical performance.37,43  Dr. Mohile’s research team prospectively evaluated the 
grade 3-5 toxicity rate of 100 consecutive participants that underwent GA and GA-driven 
recommendations.  These participants were older (mean age 80, 70-91), but had similar cancer 
characteristics to the published observational cohort.5   Grade 3-4 toxicities occurred in 33 of 100 
participants within 3 months of chemotherapy initiation.  No participants developed grade 5 
toxicities.  This is lower than the rate reported in the CARG study of patients whose physicians did 
not receive GA results and did not implement GA-driven recommendations.5  On average, 80% of the 
recommended GA-driven recommendations were implemented with an average of 6 recommendations 
per participant (range 3-15).  At the annual URCC Research Base meeting in September of 2012, site 
PIs expressed unanimous interest in the current proposal and >90% stated that they have the resources 
necessary to follow through with GA-driven recommendations (e.g., availability of 
PT/OT/Nutrition/Social work). 
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1.8.6. The research team has experience with interventions that affect decision-making for 
treatment of advanced cancer.  Dr. Epstein, an expert in patient-centered communication, has used 
multi-method research to study patient-physician interactions involving analyses of patient and 
physician surveys and medical record audits.  His research team has helped to establish that patient-
centered communication is associated with improved information exchange, reduced symptom 
burden, lower heath care costs and greater patient involvement in decision-making.98-100  The 
measures to assess decision-making in Dr. Epstein’s NCI-funded RO1 (PI is a co-investigator) have 
been adapted for patients with advanced cancer.101,102  Dr. Dale, Chief of Geriatrics and Palliative 
Care at the University of Chicago, has expertise in medical decision-making, quality of life, and 
frailty, and has studied the role of emotions in decisions about screening, diagnosis, and treatment of 
cancer in older persons.  He and Dr. Mohile have collaborated on a study that evaluated patient-
physician decisions with regard to treatment of advanced prostate cancer.103  The patient and 
physician measures utilized in this proposal to capture decision-making for cancer treatment are 
adapted from this prior work. 
1.9. Summary of Background, Innovation, and Public Health Significance.  
Historically, oncology clinical trials have excluded older patients with other health conditions and have 
included only limited numbers of patients aged 70 and over.14  Underrepresentation of older adults occurs 
in clinical trials examining the safety and efficacy of chemotherapy regimens as well as other treatments 
such as monoclonal antibodies and targeted agents.117-120  Older cancer patients are at an increased risk of 
treatment complications, and there is no standard approach to implementing interventions to reduce 
toxicity.  Common assessment instruments in oncology (e.g., Karnofsky performance status scores) do 
not address critical geriatric domains that predict morbidity and mortality in the older patients (e.g., 
functional status, comorbidity, social support).  A geriatric assessment (GA) includes a compilation of 
reliable, validated tools to assess health status.   Several studies, including a multicenter Cancer and Aging 
Research Group (CARG) trial, have demonstrated that items in a GA can predict severe chemotherapy 
toxicities in older cancer patients.5  However, no consensus exists on how to translate information from 
the GA into targeted interventions that have the potential to prevent adverse outcomes (e.g., toxicity, 
functional decline, lower quality of life) for older cancer patients.  The vast majority of oncology 
physicians have not adopted the use of GA and GA-driven recommendations for older adults with cancer, 
largely because of lack of knowledge on how to interpret GA results and on whether GA-driven 
recommendations can improve clinical outcomes.   
1.10 . Study Participants 
The study involves adult human subjects. 
NCORP practice sites will be randomized within a 2-arm cluster randomized design utilizing NCORP 
practice sites as the unit of randomization.  A NCORP practice site will be defined as any practice 
location within an overarching NCORP designation where oncology physicians and study staff work 
independently (i.e., do not cross over into another site).  
Study participants will include: 
• Oncology physicians at NCORP practice sites. Oncology physicians can work with designated staff in
the clinic to carry through specific study procedures outlined in the protocol, but staff are not considered
study participants and will not be enrolled.
• Participants will complete surveys.  Participants will all have advanced cancer and various levels of
functional status.
2. STUDY OBJECTIVES
This is a cluster randomized study within the URCC NCORP Research Base network evaluating whether 
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GA summary plus GA-driven recommendations can improve clinical outcomes in older adults starting a 
new treatment  regimen (i.e., chemotherapy or other agents with similar prevalence of toxicity) for the 
current diagnosis of an advanced solid tumor malignancy (advanced cancer).   
2.1. Primary Aim 
Our primary aim is to determine if providing information regarding GA plus GA-driven recommendations 
to oncology physicians reduces clinician-rated grade 3-5 toxicity in participants aged 70 and over with 
advanced cancer starting a new treatment regimen. The regimen must include a chemotherapy drug or 
other agents that have similar prevalence of toxicity (see section 4.2.1c).    
The primary efficacy endpoint for this study is the proportion of participants that experience grade 3-5 
toxicity within 3 months of starting a new treatment regimen. 
2.2. Secondary Aims 
2.2.1. The principal secondary endpoint for this study is the proportion of participants that are alive at 
6 months after study entry. 
2.2.2. Additional efficacy measures will evaluate whether providing oncology physicians with 
information regarding GA summary and GA-driven recommendations influences clinical care of 
older patients receiving treatment for advanced cancer. 
We will compare treatment decisions (as measured by relative dose intensity of the agents 
administered in the first cycle).  We will also compare the number and type of GA-driven 
recommendations implemented for older participants starting a new treatment regimen for advanced 
cancer.  
2.3. Exploratory Aims 
2.3.1. An exploratory aim is to determine whether providing the oncology team with GA information 
and GA-driven recommendations can slow functional and physical decline in older patients with 
advanced cancer.   
Functional status will be measured with self-reported Instrumental Activities of Daily Living score.  
Physical performance will be measured with the OARS Physical Health Subscale, and the Short 
Physical Performance Battery.  
2.3.2. In collaboration with the National Cancer Institute, other exploratory aims will evaluate the 
role of patient-reported CTCAE in the clinical care of older adults receiving cancer treatment.  These 
aims include the following: 
2.3.2a. To examine the association between patient-reported symptoms (as measured by PRO-
CTCAE) and geriatric domains (as measured by geriatric assessment).  
2.3.2b. To compare PRO-CTCAE and physician-rated CTCAE in a sample of older patients 
receiving chemotherapy or other agents with similar prevalence of toxicity. 
2.3.2c. To examine the association between PRO-CTCAE and treatment decisions. 
2.3.2d. To examine the association between PRO-CTCAE and adverse outcomes (early 
discontinuation of chemotherapy or other agents with similar prevalence of toxicity, 
hospitalizations, and mortality). 
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3. STUDY DESIGN
See Study Schema and Design for summary. 
3.1. Choice of Comparators 
Because GA is not performed by community oncology physicians and this study ultimately will allow 
patients and oncology physicians to choose their cancer treatments, a usual care comparator arm is 
appropriate and will allow for the accurate and appropriate assessment of how the intervention can reduce 
toxicities.  This study design is similar to previous studies that evaluated the impact of providing 
summarized Health Related Quality of Life (HRQoL) information to patients and oncology physicians on 
communication and outcomes.  Usual care was the comparator arm in these cluster randomized trials.104 
3.2. Choice of Study Design 
The study is designed as a cluster randomized trial because a care of service model is applied to each 
participant by the oncology team.  If a cluster randomized design were not undertaken, there would be 
contamination in that oncology physicians could choose the care of service model if they were exposed to 
participants randomized to both arms.  Given rapid changes that can occur in oncology practice with new 
supportive care and treatment agents, it is important to compare outcomes in the same time frame as 
would be possible in a cluster randomized study design compared to a “pre” versus “post” intervention 
study design. 
4. PARTICIPANT ELIGIBILITY
4.1. Entry Criteria for Oncology Physicians 
Oncology physicians must work at a NCORP practice site with no plans to leave that NCORP 
practice site or retire at the time of enrollment into the study. 
4.2. Entry Criteria for Patients 
4.2.1. Inclusion Criteria for Patients 
4.2.1a. Male or female 70 years of age or older. 
4.2.1b. Diagnosis of an advanced solid tumor malignancy (advanced cancer) or lymphoma.  In 
most situations, this would be a stage IV cancer.  Patients with a diagnosis of stage III cancer or 
lymphoma are eligible if cure is not possible or anticipated.  Clinical staging without pathological 
confirmation of advanced disease is allowed. 
4.2.1c. Plan to start a new cancer treatment regimen within 4 weeks from time of baseline 
registration.  The treatment regimen is up to the discretion of the treating oncology physician. The 
regimen must include a chemotherapy drug or other agents that have similar prevalence of 
toxicity.     
Patients who will receive monoclonal antibody therapy or other cancer therapies (e.g., 
tyrosine kinase inhibitors) are eligible if the other agents present a prevalence of toxicity 
similar to chemotherapy.  These therapies can be used in combination with chemotherapy, as 
a single agent, or in combination with each other.    
* Chemotherapy will be defined as cytotoxic drugs; in addition, agents (e.g., monoclonal
antibodies and targeted agents)  that have a prevalence of grade 3-5 toxicity in older patients
similar to chemotherapy (>50%) will be allowed. A list of allowable agents (single and in
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combination) meeting this toxicity criteria will be available on the URCC NCORP Research Base 
website as part of the study materials.  Given the rapidly changing landscape of new drugs for 
cancer, the study team led by the PI will update the list accordingly after reviewing the toxicity 
profile of new therapies.   If the potentially eligible participant is to receive an approved drug 
or regimen not on the list, contacting the URCC NCORP Research Base study team is 
required for approval prior to participant enrollment.    
Patients who are receiving approved cancer treatment in combination with radiation are 
eligible.   
A patient may also be enrolled on a treatment trial and participate in this study, if all other 
inclusion and exclusion criteria are met.   
4.2.1d. Plan to be on chemotherapy or other allowable treatment (as per 4.2.1c) for at least 3 
months (minimum 70 days) and be willing to come in for study visits. 
The plan for treatment should be for at least 3 months at time of study enrollment.  The treatment 
can stop earlier during the study at the discretion of the physician and patient (e.g., due to 
progression as noted through imaging, toxicity, or patient preference).  
4.2.1e. Have at least one geriatric assessment domain meet the cut-off score for impairment other 
than polypharmacy per Table 2. 
4.2.1f. Able to provide informed consent, or if the oncology physician determines the patient to 
not have decision-making capacity, a patient-designated health care proxy (or authorized 
representative per institutional policies) must sign consent by the baseline visit.  If the participant 
is found to be impaired on the Blessed-Orientation Memory Concentration Test (BOMC) during 
screening; they must have a health care proxy or authorized representative to be eligible to enroll. 
4.2.1g. Participant has adequate understanding of the English language because not all GA 
measures have been validated in other languages. 
4.2.2. Exclusion Criteria for Patients 
4.2.2a. Have surgery planned within 3 months of consent.  Patients who have previously received 
surgery are eligible. 
4.2.2b. Presence of symptomatic brain metastases at time of study consent process.  Patients with 
history of treated brain metastases are eligible if they are not symptomatic at the time of study 
enrollment. 
5. IDENTIFICATION, RECRUITMENT, AND CONSENT PROCEDURES
Patients will be recruited from the outpatient community oncology practices affiliated with the URCC 
NCORP Research Base network.  The results of this study will be generalizable to the majority of older 
adults with cancer because it will include older cancer patients from diverse backgrounds and at varying 
health statuses who receive treatment in the community. 
5.1. Study Participants 
Study participants will be identified by their treating oncology physicians, who enroll in the study, the 
nurses that work with the enrolled oncology physicians and the clinical research associates (CRA).  The 
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CRAs will work closely with the oncology physicians and nurses to identify those patients aged 70 and 
over with advanced cancer that are to begin  a new cancer treatment regimen (see section 4.2.1c).  The 
oncology physician then confirms if the patient is an eligible study candidate for all requirements other 
than GA impairment by completing the eligibility checklist with the CRA and signing it.  The oncology 
physician or CRA will introduce the study to the eligible patients and/or their designated health care 
proxies or authorized representatives (per institutional policies), and will provide them with an IRB 
approved study brochure and consent to review.  Adequate time will be provided to the patient and/or 
designated representative to read the consent.  The CRA, the oncology physician, and the nurses are 
available to answer any questions the patient and/or authorized representative may have about any aspect 
of the study prior to consenting and throughout the entire study period.  Patients and/or their designated 
authorized representative may choose to sign the informed consent document immediately on the day the 
study information is presented to them or they may choose to take the consent form home and discuss it 
with others; then if they want to participate in the study, they can provide signed consent forms the next 
time they meet with the CRA or oncology physician.  Patients and/or their designated authorized 
representatives must sign consent prior to the oncology physician initiating the new cancer treatment 
regimen. 
5.1.1. Informed consent will be obtained from the patient, unless they lack capacity to provide 
consent.  If a patient lacks capacity, a health care proxy and/or authorized representative will be 
required to sign consent per institutional and/or local policies on consent for 
incapacitated/decisionally impaired patients.  If the patient does not have an appointed health care 
proxy or authorized representative (per institutional policies) on or before the baseline visit, he/she 
will not be enrolled onto the study.  All consent documents will be signed by the patient and/or 
designated health care proxy/authorized representative and maintained in the patient record with 
copies provided to the patient and/or designated health care proxy/authorized representative.  
5.1.2. The screening measures will then be performed.  Those with a diagnosis of dementia, as noted 
in their medical record or diagnosed by a physician, or who meet the cut-off score for impairment on 
the cognitive screen (score of 11 or more on Blessed Orientation-Memory-Concentration Scale 
(BOMC)) can be included if a designated health care proxy (or authorized representative per 
institutional policies) selected by the participant signs consent.  The goal of the intervention is to 
improve outcomes of older cancer patients with all underlying health conditions including cognitive 
issues.  Therefore we will include these patients and will conduct the assessments with assistance of 
the proxy. 
5.1.3. Ethical standards for human subjects will be strictly followed in accordance with local policies 
and/or institutional review board requirements on the enrollment of adult decisionally incapacitated 
research participants and permission of authorized representatives (e.g., health care proxy). If the 
policy in 5.1.2 (as approved by the NCI and URCC IRB) violates local policies, the URCC NCORP 
Research Base should be notified if patients with cognitive impairment are not able to be enrolled by 
the site.    
5.1.4. Current, state, federal, and institutional regulations concerning informed consent will be 
followed.  Participation in this study is voluntary.  Participants are free not to take part or to withdraw 
at any time, for whatever reason, without risking loss of present or future care they would otherwise 
expect to receive.  Sections 11.4.1c and 14 include withdrawal procedures.     
5.1.4a In the event that a participant does withdraw from the study, the information they have 
already provided will be kept in a confidential manner.  Data will be used unless 
permission is revoked in writing and sent to their oncology physician or the URCC study 
team.  Site oncology physicians should forward any such correspondence to the URCC 
Research Base. 
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5.2. Oncology Physician Recruitment  
Because oncology physicians are being recruited and enrolled from sites across the country by the URCC 
Research Base, oncology physicians will read and agree to participate either via Research Electronic Data 
Capture (REDCap) or on paper if REDCap is not a feasible option.  REDCap is a software toolset (see 
Section 16.3 for more information) for electronic collection and management of research and clinical trial 
data developed by Vanderbilt University.  Oncology physicians will be enrolled prior to enrolling 
(screening registration) their first eligible patient.  Staff from the URCC Research Base (including the PI) 
will be available to answer any questions the oncology physicians may have over the phone.  Procedures 
for the oncology physicians are minimal risk and involve completing surveys which will be de-identified 
and identifying patients for the study. 
Oncology physicians will provide baseline demographic information, fill out a baseline survey that 
evaluates preferences for decision-making, and help identify their own patients who may be eligible for 
the study. The baseline survey can be completed online via REDCap or on paper if REDCap is not 
feasible.  REDCap will securely store the oncology physician’s email address for surveys.  In addition to 
the email address, the only personal identifying information the oncology physicians will provide will be 
their name, age, ethnicity, and the name of the clinic where they work.  The oncology physician will be 
assigned an ID number, which will be used to link their surveys with those of their patients enrolled in the 
study.   
The participation of oncology physicians in the research study meets criteria for “waiver of 
documentation of consent” because the research involves no more than minimal risk to the oncology 
physicians and there are no procedures for the oncology physicians that would normally require written 
consent outside of the research context. Therefore URCC Research Base is responsible for tracking and 
collecting physician agreement to participate in the study. Hence, the NCORP site staff do not need to 
consent their participating Physician. 
6. REGISTRATION
6.1. Prior to entering participants, either oncology physicians or patients, on this protocol, the following 
must be on file at the URCC NCORP Research Base: 
6.1.1. Documentation of IRB approval in the form of an HHS Protection of Human Subjects 
Assurance Identification/IRB Certification/Declaration of Exemption (formerly Form 310), CTSU 
approval form or signed letter from the IRB. 
6.1.2. A copy of the institution’s IRB-approved informed consent document. 
6.1.3. Written justification for any substantive modifications made to the informed consent 
concerning information on risks or alternative procedures.    Written justification should be provided 
also regarding changes related to the inclusion or consent of decisionally incapacitated participants 
(see sections 5.1.2 and 5.1.3). 
These documents are submitted to: 
Cathleen_Lesniewski@urmc.rochester.edu 
OR 
Ms. Cathy Lesniewski 
URCC NCORP Research Base 
Saunders Research Building  
265 Crittenden Blvd 
CU 420658 
Rochester, NY  14642 
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6.2. Registration Requirements 
6.2.1. Timing of Registration: See section 11, Outline of Study-Specific Procedures. 
6.2.2.  Screening Registration 
6.2.2a. Go to the URCC NCORP Research Base website at URCC-NCORP.org and enter the 
information outlined below.  

If you experience difficulties you may call 585-275-1364 at the URCC NCORP Research
Base to verbally give the URCC registrar the information below.

The following information will be requested:

NCORP Affiliate Name

URCC Protocol

Most recent IRB approval date (either initial or annual, NOT the date of approval of
an amendment)

NCORP Practice Site

Name and telephone number of person registering study participant

Confirmation that consent form has been signed and by whom

Confirmation of participant screening ID if participating in another URCC study

Participant’s Physician Name (confirms that oncology physician has been enrolled)

Participant’s identification
First and last initials
6.2.3.  Baseline Registration 
6.2.3a. Go to the URCC NCORP Research Base website at URCC-NCORP.org and enter the 
information outlined below.  

Baseline registration can be completed up to 2 work days prior to the scheduled baseline
visit.

The geriatric assessment and baseline registration should be completed within 4 weeks after
the screening visit.

If you experience difficulties you may call 585-275-1364 at the URCC NCORP Research
Base to verbally give the URCC registrar the information below.

The following information will be requested:

NCORP Affiliate Name

URCC Protocol

Most recent IRB approval date (either initial or annual, NOT the date of approval of
an amendment)

NCORP Practice Site

Name and telephone number of person registering study participant

Confirmation that all eligibility requirements have been met

Confirmation that consent form has been signed and by whom

Participant’s screening ID

Participant’s Physician Name (confirms that oncology physician has been enrolled)

Participant’s identification

First and last initials

Birth date (MM/DD/YYYY)

Gender

Race/Ethnicity

Five-digit zip code

Payment code
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
Confirmation of participant assessment scores for the Blessed-Orientation
Memory Concentration Test (BOMC) and the Geriatric Depression Scale (GDS)

Planned chemotherapy or other approved agents with similar toxicity prevalence

Date of Baseline Visit

An email confirmation of registration will be forwarded by the URCC Research Base.
6.3. A total enrollment of 700 participants is planned. 
6.4. This protocol is open only to affiliates of the URCC NCORP Research Base who provide written 
documentation of IRB approval.  There will be no accrual at the URCC NCORP Research Base itself. 
7. OUTCOMES
7.1.  Clinical Outcomes 
7.1.1. Toxicity.  Toxicity will be captured in a standardized manner using the NCI Common 
Terminology Criteria for Adverse Events (V4.0).  The NCI’s Common Terminology Criteria for 
Adverse Events (CTCAE; http://ctep.cancer.gov/reporting/ctc.html) is a longstanding empirically 
developed “dictionary” or lexicon, designed for use in clinical trials to aid clinicians in detecting and 
documenting an array of adverse events (AEs) commonly encountered in oncology.  An AE is any 
unfavorable sign (including an abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medical treatment or intervention that may or may not be considered 
related to the medical treatment or intervention under investigation.  The AE may be either 
unexpected or expected.  
An AE is a term that is a unique representation of a specific event used for medical documentation 
and scientific analyses of treatment efficacy and tolerability.  Each AE is typically graded on a scale 
of 1 (mild) to 5 (death related to AE), though a grade 5 is not relevant for some AEs, such as hair loss 
or skin itching.  The reporting requirements for AEs are generally protocol-specific and may be 
divided into two types.  The first is the protocol-specific AEs to be addressed at designated evaluation 
intervals. The second is the pertinent positive clinical signs, symptoms, and laboratory results 
obtained as part of routine care of patients.  The CTCAE is maintained by the NCI’s Cancer Therapy 
Evaluation Program (CTEP).  The CTCAE is currently in its fourth version.  
Ideally, the CRA will be present at each scheduled visit where toxicities are captured and graded by 
the oncology team.  In the event that the CRA is unable to be present at the visit, s/he will need to 
follow-up with the oncology team to verify the toxicities.  Treatment dosing administration as well as 
grade 2-5 treatment toxicities will be captured for 3 months after study enrollment.  Toxicities will be 
captured for all treatments provided within the first 3 months. Grade 2-5 treatment toxicities and 
treatment dosing administration will be captured between 3-6 months only for those participants who 
remain on any of the same treatment drugs that they were receiving at study initiation (including for 
those who treatment dosing was modified or delayed).    
Per participant, the CRA will complete the forms capturing dosing administration and grade 2-5 
toxicities for each treatment cycle to summarize the above information, which will be sent to the 
Research Base after study visits.  Treatment dosing administration and toxicities will be captured 
either by standard forms or electronically through REDCap.  REDCap (see section 16.3) will capture 
exactly the same information as the forms and will be available as a data entry option for capture of 
treatment and toxicity information.   
The medical record will also be reviewed in order to capture each clinical encounter (scheduled or 
emergency visits).  This will include a review of the clinic notes, emergency room visits, and 
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hospitalizations (i.e., emergency room and hospitalization discharge summaries).  If the participant 
seeks emergency care outside of the primary institution, the participant’s permission will be obtained 
to review these outside records.  Details regarding the overall category of toxicity (hematologic or 
non-hematologic), specific type of toxicity, and the rationale for the toxicity grade will be captured.  
Dose reductions, dose delays or discontinuation of the treatment course will also be captured, as well 
as the cause (i.e. relationship to toxicity).   
7.1.2.  Cancer Treatment Decisions.  The NCCN guidelines105 will be utilized to capture the 
standard dosing of treatment regimens.  The planned regimen (individual drugs, doses, and schedule) 
will be captured at the beginning of the study from the primary oncology team.  The cumulative 
dosages per unit time of the individual drugs in the regimen will be calculated: (total mg of drug in all 
cycles/m2 body surface area)/(total days of therapy/7).  The denominator is based on total days on 
treatment (from day 1 of cycle 1 through 1 cycle length after the date of the last treatment), reflecting 
all dose delays.  The relative dose intensity (RDI) is calculated as the ratio of the amount actually 
delivered to the amount intended based on standard guidelines.  The actual dose delivered (in the 
numerator of RDI) will account for  dose reductions.  The RDI is calculated for each drug in a 
multidrug regimen, which are averaged to derive the average RDI.  The doses will be collected in the 
forms completed by the CRAs at the sites.  All calculations will be performed at the Research Base.   
7.1.3. Survival.  We will capture survival through the participant’s medical record and verification 
with the primary team.  We will follow participants for survival for 12 months after enrollment.  We 
will obtain the date, location of death, and cause of death. If a site becomes aware that a study 
participant is now deceased, they should complete the Survival Status form which is available on the 
URCC NCORP website. Otherwise sites will be contacted approximately 1 year after each participant 
was enrolled to assess survival and asked to complete this form. We will also verify information with 
Medicare claims data if the participant provided permission to do this through initial consent (see 
Section 7.2.3). 
7.2. Data Sources 
7.2.1. Participant Surveys.  Participants will complete surveys prior to the start of treatment and at 
4-6 weeks, 3 months, and 6 months.  We are sensitive to respondent burden and have minimized the
number of items to be completed in a single sitting. All surveys have been utilized in our pilot work
with older patients with cancer and other age-related health conditions.  In a recent study, 98% of
patients with non-small cell lung cancer with a median survival of 9 months completed a baseline
battery similar in length, and 70% and 64% of those who were still alive were able to complete
assessments at 3 and 6 months, respectively.106,107  As is often true for patients with advanced disease,
missing data were not random; sicker patients tended not to complete surveys. We have included
approaches to missing data in section 11.4.1c. and in the statistical section of the protocol. Non-
completion of surveys due to illness or fatigue should not be considered a patient withdrawal.  Every
effort should be made to collect participant survey information in person and objective GA
information.   If survey and GA information cannot be collected (due to participant illness and
fatigue), CRA forms regarding treatment and toxicity information should still be completed at the
appropriate time points.   In addition, clinic notes, treatment records, and emergency
room/hospitalization discharge summaries should also be provided.   Hospitalization discharge
summaries are not required for participants in hospice or end of life care.
7.2.2. Oncology Physician Surveys.  Oncology physicians will complete a baseline survey prior to 
or when their first patient consents to the study and a brief follow-up survey at the end of the study.  
After the baseline visit, oncology physicians will be asked about potentially important covariates or 
moderators, including disease and treatment characteristics.  They will also complete a brief survey 
about decision-making after each follow-up visit. When an oncology physician’s study participation 
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is near completion (e.g., all their study participants are off study, they are moving or leaving the 
practice) the oncology physician will complete the Final Physician Survey found on the NCORP 
website with a separate version for the control and the intervention sites. 
7.2.3. Chart Abstraction and Claims.  Clinic notes, treatment records, and emergency 
room/hospitalization discharge summaries will be requested to validate treatment dosing and toxicity 
information.  Hospitalization discharge summaries are not required for participants in hospice or end 
of life care.  If there is missing information or conflicting medical information from the surveys, we 
will obtain additional medical records in order to verify information about disease location, 
pathology, stage, and metastases from charts. We will request information from the CRA on the final 
treatment recommendations made and implemented. In order to assess health care utilization (e.g., 
adverse events such as hospitalizations) for future work on examining cost-effectiveness of the 
intervention, permission to obtain Medicare claims in the future will be asked on the consent form. 
Claims will not be obtained for any individual participant until the participant is off study.  Claims 
information will be collected for all participants that agreed per the consent, including those who have 
completed the study or have withdrawn from the study. All consent and research procedures for 
obtaining Medicare claims will be followed:  http://www.cms.gov/Research-Statistics-Data-and-
Systems/Computer-Data-and-Systems/Privacy/Researchers.html 
Permission to obtain claims is voluntary.  Patients will be able to decline this procedure at the time of 
consent.  Declining consent for obtaining claims from Medicare for future research to examine cost-
effectiveness, quality of care, and health care utilization does not preclude patients from participating 
in the rest of the study. 
8. MEASURES TO BE COLLECTED
An overview of measures is provided here.  A detailed description of each measure including a summary   
table is provided in Appendix A. 
We have piloted all measures.  In total, geriatric assessment measures that are filled out by the participant 
require approximately 20 minutes of time.  The additional measures (e.g., PRO-CTCAE) captured at 
baseline require an additional 15 minutes of time.  We have incorporated flexibility with timing in order 
to reduce participant burden.  The follow-up surveys require about 30 minutes of time in total. 
Participants may complete the first geriatric assessment in clinic at time of consent or in clinic before the 
next visit with the oncology physician.  They may choose to complete measures at home in between 
visits.  The geriatric oncology clinic at the University of Rochester routinely captures these measures as 
part of clinical care. 
Table 1: Participant and CRA Measures: 
   Demographics 
   Medical Characteristics and Treatment 
   Labs/Lab Form 
   Com-meds/Polypharmacy 
   Geriatric Assessment 
- Assessments by CRA
- GA Participant Packet
    Decision-Making Preferences
   PRO-CTCAE 
   Clinician-rated CTCAE (Primary Outcome) 
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The assessments performed by the CRA and associated surveys take about 30 minutes of time in total 
(including physical performance and cognitive tests).  Any person at the practice site can be trained by 
Research Base staff to do the GA.  The GA does not need to be performed by the oncology physician. 
The oncology physician assessments will be done either on paper or through REDCap, whichever the 
oncology physician prefers.  The baseline and end of study assessments take no longer than 10 minutes 
and after the initial participant visit, the decision-making form (to assess factors that influenced decisions) 
takes only a few minutes to complete. 
Components of Geriatric Assessment (Participant) 
Assessment tools comprising the comprehensive GA are listed in Table 2.  The various assessment tools 
were selected based upon extensive data in the geriatric literature demonstrating predictive value as well 
as feasibility data in multiple studies of elderly patients with cancer.  Other than the cognitive and 
physical performance measures, the assessments are self-administered.  Participants who cannot complete 
the assessment on their own will receive assistance from study personnel or a caregiver.  The GA is 
performed before baseline registration.  Follow-up GA measures are collected at 4-6 weeks, 3 months, 
and 6 months.   
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Table 2: Components of the Comprehensive Geriatric Assessment 
***Captured before baseline registration 
Abbreviations: ADL (Activities of Daily Living); Blessed OMC (Blessed-Orientation Memory Concentration 
Test); GAD (Generalized Anxiety Disorder 7-Item Scale); GDS (Geriatric Depression Scale); IADL (Instrumental 
Activities of Daily Living); QoL (Quality of Life). 
8.2. Other Clinical Measures (Participant) 
8.2.1. Sociodemographics.*** Participant age, race and ethnicity, gender, highest level of education 
achieved, employment status, marital status, and presence of a living companion will be captured. We 
will also assess understanding of disease. 
8.2.2. Tumor and Treatment Characteristics. The tumor stage, previous surgery or radiation, 
previous cancer treatments, current cancer treatment plan including chemotherapy (type, dosing, and 
schedule), monoclonal antibody treatment, targeted agents, and supportive care medications will be 
captured by the CRA. 
8.2.3. PRO-CTCAE.  (from:  http://outcomes.cancer.gov/tools/pro-ctcae_fact_sheet.pdf)  There is 
growing awareness that collecting symptom data directly from patients using patient reported 
outcome (PRO) tools can improve the accuracy and efficiency of symptomatic AE data collection.  
This is based on findings from multiple studies demonstrating that physicians and nurses 
DOMAIN 
TOOL 
SCORE SIGNIFYING 
IMPAIRMENT 
Physical function 

Activities of Daily Living

Instrumental ADLs

Fall History

OARS Physical Health

Any ADL deficit

Any  IADL deficit

Any history of falls

A lot of difficulty with any task
Objective 
physical 
performance 

Short Physical Performance
Battery

Timed “Up and Go”***

≤ 9 points

>13.5 seconds
Comorbidity 

OARS Comorbidity***

Participant answered “yes” to ≥3
chronic illnesses

One illness interferes “a great deal”
with QoL
Nutrition 

Body Mass Index

Mini Nutritional Status***

Weight loss***

<21 kg/m2

≤ 11 points

>10% from baseline weight
Social support 

OARS Medical Social
Support***

Participant answers one of the social
support questions indicating less than
adequate support for care
Polypharmacy 

Polypharmacy

Lab***

≥5 regularly scheduled prescription
medications OR

Any high-risk medication OR

Creatinine clearance <60 ml/min
Psychological 

GAD-7 ***

Geriatric Depression Scale

> 10 points

≥5 points
Cognition 

Blessed OMC***

Mini-Cog

>10

0 words recalled OR 1-2 words
recalled + abnormal clock drawing
test
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underestimate symptom onset, frequency, and severity in comparison with patient ratings.  For 
example, in a study of men with prostate cancer enrolled in a Phase II clinical trial, physician 
reporting was neither sensitive nor specific in detecting common chemotherapy symptomatic adverse 
effects.108 
In the field of pain management, it has long been recognized that only the patient can accurately 
report the onset, severity and duration of pain and its impact upon function.  This principle extends to 
other symptoms, such as fatigue, erectile dysfunction, and xerostomia (dry mouth), which can be 
found in the CTCAE.  The other advantages of a PRO complement to the CTCAE are discussed in an 
article by Trotti et al.109  
The NCI’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse 
Events (PRO-CTCAE) system provides a platform to collect patient reports of symptoms they are 
experiencing while undergoing treatment, for the purpose of enhancing adverse event (AE) reporting 
http://outcomes.cancer.gov/tools/pro-ctcae.html).  To date, 81 symptoms of the CTCAE (version 4) 
have been identified as amenable to patient reporting. These symptoms have been converted to patient 
terms (e.g., CTCAE term “myalgia” converted to “aching muscles”).  
For purposes of this project, core items will be assessed along with items related to geriatric 
functioning.  Participants will complete these surveys at baseline, 4-6 week, 3 month, and 6 month 
time points. 
8.3 Decision-Making Assessments (Participant and Oncology Physician) 
8.3.1. Participant Assessments. We will collect measures to assess the processes of decision-making 
for treatment.  The measures chosen for this study are validated tools designed to measure how 
participants’ approach the decision-making process.  Validated tools will measure patient-centered 
autonomy-supportive oncology physician behaviors such as whether the participant feels that the 
oncology physician understands his/her perspective, and provides choices and options.  
8.3.2. Oncology Physician Assessments.  We will collect information on demographics and 
decision-making preferences.  Oncology physicians will be presented with a clinical scenario of 
elderly cancer patients with a variety of geriatric-related impairments (i.e., physical frailty, cognitive 
impairment).  A series of questions will follow each vignette inquiring about the likelihood of the 
oncology physician to offer chemotherapy in the scenario.  After the study is over, physicians will be 
asked to complete a brief follow-up survey. After the baseline clinical encounter, oncology physicians 
will complete a short (<10 question) survey follow-up requesting information on the treatment plan 
for the participant and factors that influenced how the decision was made.   
9. NCORP PRACTICE SITE RANDOMIZATION
A practice site is defined as any practice location within an overarching NCORP designation where 
oncology physicians and study staff work independently, i.e., do not cross over into another site.  Practice 
sites will be randomized to one of the two study arms by means of a computer–generated randomization 
table.  Past accrual to URCC studies will be used to stratify each practice site as a large accruing (20 or 
more accruals/year) site or a small accruing practice site in order to assure balance in the randomization.  
The randomization process will be determined using R software provided by Dr. Charles Heckler, the 
lead biostatistician of the URCC NCORP Research Base.   
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10. INTERVENTION OVERVIEW FOR PHYSICIANS
Practice sites will be notified if they are in the intervention arm by URCC Research Base staff. At the 
sites randomized to the intervention arm, oncology teams will implement the intervention.  The oncology 
physician is required to review the GA information and decide upon recommendations.  He/she can 
designate an advanced practice practitioner (APP) (e.g., nurse practitioner (NP) or physician assistant 
(PA))or an oncology fellow to assist with intervention procedures.  The URCC NCORP Research Base 
must be informed if an APP or a fellow is participating prior to any study procedures being implemented.  
Designated APPs and fellows, if at an intervention site, must complete intervention training procedures.  
Sites will be asked by the Research Base staff if there are members on the oncology team who may 
conduct the baseline visit at the time of IRB approval or after a physician is recruited.   These members 
will be contacted and trained appropriately for their group assignment (i.e. control, intervention).  
Prior to implementing the intervention, oncology physicians and designees will receive training on how to 
best utilize GA information in clinical practice for older adults with cancer.   The training session 
provides a brief overview of the intervention information and can be completed through a web 
conference, telephone call, or as a paper “sign-off” documenting review of the materials.  The training 
materials were developed with resources from Drs. Mohile’s and Hurria’s geriatric oncology lectures.   
The CRAs and/or research nurses at sites randomized to the intervention arm will be trained to utilize the 
mycarg.org website to derive a summary of GA scores and a list of targeted GA-driven recommendations.  
This information will be printed by the site CRAs for the oncology physician who will “sign off” that 
he/she has received and reviewed the information.    
Study or clinical staff can assist the oncology physician in checking which recommendations were 
considered and facilitating implementation of GA-driven recommendations. The oncology physician can 
identify which of the recommendations he/she thinks are appropriate and high priority for the participant.  
They do not all need to be implemented at the time of the visit but implementation should occur before the 
4 week visit.    
Selection of GA recommendations could occur prior to the baseline visit or during the baseline visit in 
conjunction with the participant and/or caregiver.  It is strongly preferred that the oncology physician 
conduct the baseline study visit.   The baseline study visit can be conducted by the physician in 
conjunction with the APP or fellow.  If the oncology physician is not available prior to the start of the 
new treatment regimen, an APP or oncology fellow may conduct the baseline study visit.  The APP 
and/or oncology fellow must have completed intervention training prior to the baseline study visit.  If an 
APP or oncology fellow is conducting the baseline visit, the oncology physician should still determine the 
recommendations and they will need to be approved or “signed off” by the oncology physician. It is 
required that discussion occurs either in person or by telephone between the oncology physician and APP 
or oncology fellow regarding the GA information and recommendations prior to the baseline visit.   The 
oncology physician must still complete the other physician forms. The baseline surveys will capture 
which member of the oncology team conducted the baseline visit. 
Two copies of the summary and checklists should be made: one should be provided to the 
participant/caregiver and one should be retained in the study chart. Participants and caregivers should be 
provided with a copy of the GA summary and GA-driven recommendation forms prior to the baseline 
visit.  The original forms should be submitted to the URCC Research Base.   
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11. OUTLINE OF STUDY-SPECIFIC PROCEDURES
Baseline: Visit 1 – Intervention 
CRA enter GA Score on MYCARG.ORG
Print and provide GA summary and recommendations 
forms to oncology team member*
Information on cognitive impairment or depression is
included in summary.
Baseline: Visit 1 – Usual Care 
Inform oncology physician if depression (GDS) or
cognition (BOMC) assessments score ≥ 11. 
All Follow-up Visits: Visit 2, Visit 3, Visit 4   
 (Visits are 4 to 6 weeks, 3 months, and 6 months from Baseline) 
Before Visit:  Confirm participant will bring completed packets to study visit.      
During Visit: Administer cognitive and physical performance measures and complete CRA study forms.  
*Intervention Arm ONLY: CRA complete GA-driven recommendation follow-up forms at visit 2 (4-
6wks). Inform oncology physician if depression (GDS) assessment score ≥ 11.
After Visit:    Submit all forms to URCC Research Base within 7 days. 
Score GA & Complete Baseline Registration 
When participant and CRA screening forms complete, score each GA measure as per training procedures (at 
screening or beginning of baseline visit prior to study visit with oncology team).
Complete baseline registration for participant if participant has 1 or more domains that meet cut-off score for 
impairment (other than polypharmacy).
Screening:  Visit 0 
Consent patient; complete screening registration. 
If time permits, administer GA measures (cognitive, physical performance, and nutrition) to participant.
Participant complete screening packet during visit or take the screening packet & baseline packet home with them
to complete prior to the baseline visit.
CRA completes CRA screening study forms and confirms planned treatment regimen is an approved one by 
checking on the URCC Research Base list
Confirm participant plans to start a new regimen and will bring completed packet to next visit or schedule 
additional time if needed to complete at visit.
Oncology Physician Enrollment – Baseline survey on REDCAP 
Subject Identification Process  
Intervention Site (Arm 1) 
Usual Care Site (Arm 2) 

Study visit with oncology team* occurs

Oncology physician completes forms about participant

Submit all materials to URCC within 7 days.
*Oncology team member can include oncology physician, APP, or oncology fellow.   If an APP or oncology fellow is
conducting the baseline visit, the recommendations still need to be approved or “signed off” by the oncology physician. It is
required that discussion occur between the oncology physician and APP or oncology fellow regarding the GA information
and recommendations prior to the baseline visit.   The oncology physician must still complete the other physician forms.
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11.1. Procedures Prior to Screening Visit 
11.1.1. Oncology Physician Enrollment and Participation 
11.1.1a. If an oncology physician is interested in the study and meets the inclusion/exclusion 
criteria, he/she will agree to participate on paper or through REDCap (sent by the URCC 
Research Base).  
11.1.1b The oncology physician will complete a baseline survey on demographics and treatment 
preferences either on paper or through REDCap. 
11.1.1c  Ideally oncology physicians are enrolled as soon as possible.  However, an oncology 
physician can be enrolled after his/her patient is identified for the study or prior to screening 
registration for the first identified patient.   
11.1.2. Participant Identification Process 
11.1.2a. Participants: Once a site has IRB approval, the site study staff can start screening for 
participants according to the inclusion/exclusion criteria for patients (section 4.2).  Only patients 
from enrolled physicians can be registered. 
11.1.2b. Screening Log: A screening log will be kept at each participating site, where all patients 
approached for the study will be entered by site study staff.  The screening log can be completed 
on paper or through REDCap.   
11.2. Screening:  VISIT 0 
11.2.1. Participant Recruitment & Consent Process 
11.2.1a. Participants 

The site study staff will notify the patient’s oncology physician when a patient is identified
as a possible candidate for the study.  Site study staff should screen for patients who may fit
eligibility criteria for all requirements other than GA impairment.  It is anticipated that some
of the patients who are eligible will be new patients for the oncology physician.  Site study
staff should confirm that planned treatment includes either a chemotherapy agent or another
agents approved by the URCC NCORP Research Base.  Approved agents are available on a
list on the URCC NCORP Research Base website with study-related materials.  If the agent
or regimen is not on the list, contact URCC NCORP Research Base for approval. The
Research Base will review toxicity information and if approved, will add drugs to the list in
an ongoing fashion (see section 4.2.1c).

The oncology physician and/or CRA should mention the study to the patient and give out
recruitment materials.

If the patient is interested, the oncology physician and/or site study staff will explain the
study and once all aspects of the study have been discussed to the patient’s satisfaction, the
voluntary written informed consent procedures will be completed with the patient if they
choose to enroll in the study.

The site study staff can schedule a separate visit with the patient to go over consent and
initiate study procedures if more time is needed.
11.2.2. Participant Assessment Process 
11.2.2a. Once a participant has consented, screening and baseline assessments/procedures need to 
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occur prior to starting the new regimen. Site study staff can schedule a separate visit with the 
participant to complete study procedures if more time is needed.  
11.2.2b. The procedures for screening will consist of the steps below: 

Confirm that the participant’s oncology physician has been enrolled onto the study and if
not, follow procedures for enrolling oncology physicians.

Participants meeting eligibility criteria are initially registered with a screening registration
after signing consent.

Administer cognitive, physical, and nutritional assessments to the participant.

These assessments can be administered right after consent, at a separate visit
scheduled by site study staff, or just prior to the  baseline study visit.  Allow 45
minutes to perform assessments if done just prior to the  baseline study visit.

Anyone at the practice site can administer cognitive and physical assessments to the
participant as long as they have participated in the required GA training administered
by the URCC Research Base.  CRAs, clinical nurses, and technicians are all eligible
to participate in training and can complete GA study procedures.

Participant will complete all screening surveys.

Ideally the participant will complete either at the time of consent or the screening and
baseline packets can be taken home and completed before the baseline study visit. If
the participant needs assistance from site study staff to complete surveys, allow
adequate time.  Approximately 60 minutes is recommended.

Abstract required medical information from chart.
11.2.2c. The GA must be completed within 4 weeks prior to the baseline study visit with the 
oncology team.  The baseline study visit with the oncology team should be scheduled prior 
to starting the new treatment regimen. Treatment should begin within 4 weeks after the 
baseline study visit. 
11.3. Baseline:  VISIT 1 
11.3.1. Participant Assessment Process 
11.3.1.a. BEFORE BASELINE VISIT: 
Site study staff will telephone the participant to: 

Confirm that participant will be starting a new treatment regimen. If a participant decides
not to proceed with the new regimen before the baseline registration is performed,
registration should not be completed and the participant should be considered a screen
failure.

Confirm scheduled visit with the oncology team.

Confirm that the participant completed the screening surveys before the baseline study visit
and remind them to bring the surveys in with them.

Schedule the participant to come in to meet with site study staff at least 45 minutes
prior to the baseline study visit in order to complete study procedures.  Allow for more
time if participant communicates that surveys have not been completed.  Only
participants that complete GA procedures can be registered for the study.
11.3.1.b. AT THE BASELINE VISIT: 

If screening surveys have not been completed prior to the participant coming in, complete
them at this visit.

If not complete, staff should administer cognitive, physical performance, and nutrition
assessment.
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
If not complete, staff should complete CRA study forms.

If not complete, baseline surveys should be done. The baseline surveys do not need to be
completed prior to baseline registration, but should be completed on the day of the baseline
visit.  For example, participants can complete baseline surveys while receiving cancer
treatment that same day.

Score each GA measure as taught in training procedures.  If assistance is needed for scoring,
contact the URCC NCORP Research Base.

Participants that have at least one abnormal GA score other than polypharmacy can move
forward with the study.

After the GA and the above steps are complete, the baseline registration procedures can be
completed for the participant (refer to section 6. Registration).

Registration must occur prior to baseline study visit with the oncology team and prior
to starting the new treatment regimen.

Once the participant is registered, if the new treatment regimen does not get initiated,
complete the Cancer Treatment Status form.  Participants should continue to be
followed and remain on study.

Prior to the study visit with the oncology team, if depression (GDS) or cognition (BOMC)
assessments score ≥ 11, inform participant’s oncology physician as follows:

Usual Care arm -- inform oncology physician with template as per training.

Intervention arm -- information on cognitive impairment or depression is included in
summary (see section 11.3.2, Intervention Procedures).
11.3.2. Intervention Procedures (Only for sites randomized to the intervention arm) 
11.3.2.a.  AT THE BASELINE VISIT: 

After the participant has been registered for the study, enter the GA scores into mycarg.org
website or if no internet is available, contact the URCC NCORP Research Base Program
Manager to assist.

After entering the GA scores, print the built pdf packet specific to that participant.

Present GA summary form and recommendation forms to oncology team to review just prior
to baseline study visit.  The study visit must occur prior to starting the new regimen. Study
staff can assist in the completion of the forms.  Study and clinical staff can assist in
implementing GA-driven recommendations after the physician approves them.

Information on cognitive impairment or depression is included in the summary.

The oncology physician MUST review and sign the summary form and
recommendations forms.  Another team member (APP or oncology fellow) can
conduct the baseline study visit only if the physician is unavailable.   If this is the case,
the GA summary information and recommendations must be reviewed or discussed
with the oncology physician prior to the baseline study visit.

GA recommendations that are planned by the oncology physician for the participant
should be check-marked by the end of the visit.

Two copies of the GA summary and GA recommendations forms should be made: one
should be provided to the participant and one should be retained in the study chart.

The original forms should be sent to the URCC Research Base.
11.3.4. Oncology Physician Assessment for Participant: After the baseline visit, oncology 
physicians will complete a brief survey (on paper) to capture factors that influenced the decision-
making process for treatment.  Oncology physicians must complete this survey even if another 
member of the oncology team conducted the baseline study visit.    
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11.3.5. Submitting Materials to the URCC Research Base: 
11.3.5a. After the baseline visit, site study staff should ensure the forms below are completed and 
submit them to the Research Base: 

All oncology physician and participant assessments from above

All CRA study forms

Clinic note from visits

Cancer treatment plan

Intervention summary and recommendation forms (if applicable)
11.4. Follow-up Visits: 
11.4.1. Visits will occur 4-6 weeks after the baseline visit, 10-14 weeks after the baseline visit (3 
months), and 20-26 weeks after the baseline visit (6 months). 
11.4.1a. BEFORE EACH FOLLOW-UP VISIT: 
Study staff will telephone the participant to:  

Confirm scheduled visit with the oncology team.  The visit does not need to be scheduled
with the oncology physician.  The participant can choose to visit with study staff to complete
procedures on a day other than a scheduled visit with their oncology team.

Confirm that the participant completed the surveys.

Surveys must be completed during the appropriate window for each time point.  Site
study staff can either mail the follow-up surveys OR at the end of one visit, they can
provide the next round of surveys to the participants to take home with them for the
next follow-up visit.

Ideally participants will complete the survey packet at home and bring to site study
staff on the day of a routinely scheduled visit for the oncology physician or designee
(e.g., nurse practitioner) visit or during cancer treatment infusions.

If the participant needs assistance from site study staff to complete surveys on-site,
allow adequate time (45-60 minutes).

If participants cannot complete packet at home:

Participant can come in prior to office visit to complete surveys.

Participant can complete surveys during cancer treatment infusions.

If needed, the participant can meet with the site study staff at an additional time
to complete the follow-up surveys. The participants do not need to meet with the
oncology physician to complete the surveys.
11.4.1b. AT  SCHEDULED FOLLOW-UP VISITS: 

Participant: Bring in completed surveys in the follow-up packet or complete at visit.

At each visit:  Staff will review participant surveys for completion and administer the
following assessments to the participant:

Cognitive and Physical Performance

If depression (GDS) assessment score ≥ 11, both usual care arm and intervention arm
inform participant’s oncology physician with template as per training.

Complete all CRA follow-up study forms including treatment and toxicity forms.
Treatment and toxicity information should be captured consecutively.

At the 4-6 week time point:  CRAs at practice sites randomized to the intervention arm will
complete the GA-Recommendation Follow-up forms by comparing them to the GA-
Recommendation Baseline forms, clinic notes, and conferring with the oncology team if
needed to verify which recommendations were implemented.

If the participant discontinues cancer treatment  for any reason, a Cancer Treatment Status
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form should be completed and submitted to the URCC NCORP Research Base and the 
participant should continue to be followed on study. 

Site study staff will submit the following to the URCC Research Base:

All oncology physician and participant surveys

Clinic note from visits

Chemotherapy and other cancer treatment records

Emergency room or hospitalization discharge summaries

All CRA, participant, and physician study forms
Other medical records will be requested if there are discrepancies or missing information in key 
data. 
11.4.1c.  DEFINITIONS AND PROCEDURES RELATED TO ACTIVE WITH MISSING 
DATA,  LOST TO FOLLOW-UP, AND WITHDRAWAL 
Many in this study’s participant population are expected to become more ill as the study 
progresses due to the nature of their underlying cancer diagnosis.  It is understood participants 
may not be well enough to complete all study assessments or visits. Therefore, the following 
definitions are provided to account for this when capturing patient status outcomes in this 
population.   
Once a participant has completed the baseline registration, participants are considered active 
participants with missing survey data if they decline to complete surveys or CRA administered 
GA measures  or both (e.g., too ill, too tired) or they are unable to come to study visits due to 
being too ill or entering hospice.  They will be considered lost to follow up if they are unable to 
be contacted by calls and emails.  
Participants who discontinue treatment but are still being followed by the site should still be 
requested to complete study procedures (surveys and CRA administered GA measures).  If they 
decline to complete surveys or CRA administered GA measures, these participants will also be 
considered active participants with missing survey data. 
In all of the above scenarios, CRA measures collecting data from the medical record (clinic notes, 
chemotherapy flow-sheets, labs) should continue until the 3 month time point for all participants 
receiving any treatment. At the 6 month time point, treatment and toxicity data will be collected 
for participants who are continuing on any of the original treatment drugs even if dose 
adjustments have been made.    
Collected in addition to right 
shaded panel if participant 
declines to complete surveys 
but still agrees to CRA-
administered GAs 
Collected if participant declines or cannot complete surveys AND 
CRA-administered  GAs 
Nutritional
Status and
MNA
BOMC
Polypharmacy Log
Cancer Treatment
Dosage Form
Cancer Treatment
Status Follow-up
Form (if
applicable)
Mini Cog
Timed
“Up and
Go”
Physician Rated
KPS
Toxicity Outcomes

GA
Recommendation
Forms at 4-6
week visit
Short Physical
Performance
Battery

Decision Regret
Follow-up
/Physician
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The primary aim of this study requires the review of treatment toxicity through patient report and/or CRA 
review of the medical record (in collaboration with the oncology team).  Assessment of treatment toxicity 
is a routine part of clinical care.  As noted above, patients can partially or completely discontinue their 
own participation in study activities at any time without actively (verbally) withdrawing from the study 
(i.e., active participant with missing data). A withdrawal from the study is defined as a patient who 
verbally states that they no longer wish to be participating in, contacted or associated with this 
study.  Only a patient can withdraw themselves from the study. If the patient does not have cognitive 
capacity, their proxy or authorized representative can withdraw a patient from the study. CRAs cannot 
withdraw a patient from study.  
Because of the fragile patient population being studied, the patient should not be automatically assumed 
to be withdrawn from the study if they are too ill to complete surveys or if they decline to complete 
surveys or GA procedures at one or more visits or go into hospice.  The CRA should continue to obtain 
medical chart  data, as it relates to subject outcomes, treatment and toxicity outcomes (i.e., Cancer 
Treatment Dosage Form, Toxicity Outcome Forms, Cancer Treatment Status Follow-up Forms) for both 
active with missing data and withdrawal patients unless the patient provides in writing that they no longer 
wish this data to be collected. This should be provided to the UR NCORP Research Base.  These 
procedures do not require patient participation.  Research Base staff will also obtain Medicare data if 
agreed to in the patient consent. 
All data will be kept in a confidential manner.  All data will be used unless permission is revoked in 
writing and forwarded to the URCC NCORP Research Base.  Site staff should forward any such 
correspondence to the URCC NCORP Research Base. 
11.5. 
Survival Status will be recorded at approximately one year from date of participant baseline 
registration on the Survival Status form. 
12. REIMBURSEMENT
In order to improve study retention and compliance, we will compensate participants for their 
participation (i.e., time and travel).  Assessments are paid at $15.00 each and payments will be provided 
after each time point starting with the baseline visit.  Participants can receive up to $60 if all four time 
point assessments are completed. 
13. ADVERSE EVENT REPORTING
13.1. Risks from participating in this research are psychological distress from completing the 
questionnaires and the cognitive testing.   
13.2. ADVERSE EVENTS RELATED TO STUDY PROCEDURES AND NOT TO ROUTINE 
ONCOLOGY TREATMENT AND CARE will be reported using the URCC Adverse Event form. This 
form can be found on the URCC NCORP Research Base website. 
13.3. Adverse Events will be reported in accordance with the following guidelines: 
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13.4. Submit written adverse event reports in one of the following ways: 
(1) PDF by
email:
Cathleen_lesniewski@urmc.rochester.edu 
(2) By mail:
Cathleen Lesniewski 
URCC NCORP Research Base 
Saunders Research Building 
265 Crittenden Blvd 
CU 420658 
Rochester, NY  14642 
(3) By fax:
Cathleen Lesniewski 
585-461-5601
13.5. An unexpected adverse event is defined as any adverse experience, the specificity or severity of 
which is not consistent with the risk information described in section 13.1. 
13.6. A serious event refers to any event in which the outcome results in any of the following:  death, a 
life-threatening adverse experience, inpatient hospitalization or prolongation of existing hospitalization, a 
persistent or significant disability, incapacity, or a congenital anomaly/birth defect.  Important medical 
events that may not result in death, be life-threatening, or require hospitalization may be considered a 
serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize 
the participant and may require medical or surgical intervention to prevent one of the outcomes listed in 
this definition. 
13.7. ONLY serious adverse events related to the study procedures need to be reported for data and 
safety monitoring purposes.  AEs and SAEs related to routine oncology treatment and care DO 
NOT need to be reported, but will be collected on outcomes forms as per section 7.1.   
13.8. Adverse events should be reported to the local IRB as per their requirements. 
13.9. Data Safety and Monitoring 
13.9.1. All adverse events requiring reporting will be submitted to the Research Base as described in 
section 13.4.  Adverse events that are serious AND unexpected AND related will be forwarded to the 
study chair and the URCC Data Safety and Monitoring Committee (DSMC) chair immediately upon 
receipt at URCC.  Additional information may be requested upon their review. 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Unexpected 
and Expected 
Unexpected 
Expected 
Unexpected 
Expected 
Unexpected 
Expected 
Unexpected 
Expected 
with 
hospital-
ization 
without 
hospital-
ization 
with 
hospital- 
ization 
without 
hospital- 
ization 
With 
hospital- 
ization 
without 
hospital- 
ization 
Unrelated 
Unlikely 
Not 
Required 
Not 
Required 
Not 
Required 
Not 
Required 
Not 
Required 
Not 
Required 
Not 
Required 
Not 
Required 
10  
Calendar 
Days 
Not 
Required 
10  
Calendar 
Days 
10 
Calendar 
Days 
Possible 
Probable 
Definite 
Not 
Required 
10 
Calendar 
Days 
Not 
Required 
Not 
Required 
10 
Calendar 
Days 
10 
Calendar 
Days 
Not 
Required 
Not 
Required 
24-Hour; 
5 Calendar
Days 
10 
Calendar 
Days 
24-Hour; 
5 Calendar
Days 
10 
Calendar 
Days 
Hospitalization is defined as initial hospitalization or prolongation of hospitalization for ≥ 24 hours, due to adverse event related to study procedures.  
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13.9.2. All adverse events reported to URCC are entered into a protocol-specific spreadsheet.  
Adverse event rates are monitored utilizing the spreadsheet.  If a serious adverse event is being 
reported frequently, the study chair will conduct a detailed review.  The DSMC Committee Chair will 
be notified and will determine if further action is required. 
13.9.3. The URCC Data Safety Monitoring Committee (DSMC) will review study progress and 
cumulative reports of adverse events at annual meetings.  An overall assessment of accrual and 
adverse events will enable the committee members to assess whether significant benefits or risks are 
occurring that would warrant study closure.   
13.9.4. The URCC will notify the NCORPs immediately of any serious safety concerns identified by 
the DSMC.  DSMC reports will be available for download on the Research Base website. 
14. CRITERIA FOR WITHDRAWAL
If an oncology physician withdraws from study, no further patients with this oncology physician will be 
recruited.  The final physician follow-up survey should be completed at the end of the study or at the time 
of a physician withdrawing; for example, if they were to move or join another practice. Whenever 
possible, participants that have already been enrolled should complete study procedures (see section 
11.4.1c).  The URCC Research NCORP Base should be contacted to discuss follow up procedures for 
participants whose enrolled physician is withdrawing from the study. 
See section 11.4.1c for procedures related to missing data, lost to follow up, or withdrawal.  Participants 
that decline or are too ill to complete follow-up surveys should not be considered as withdrawals; instead 
they will be considered active participants with missing survey data. Due to the nature of the illness, we 
expect there will be participants that will be too ill to complete their study related procedures (e.g., 
surveys, GA procedures). In these situations, CRAs should still be collecting medical record chart review 
and completing CRA forms as per section 11.4.1c.    
Patients can partially or completely discontinue their own participation in study activities at any time 
without actively (verbally) withdrawing from the study (i.e., active participant with missing data). A 
withdrawal from the study is defined as a patient who verbally states that they no longer wish to be 
participating in, contacted or associated with this study.  Only a patient can withdraw themselves from the 
study. If the patient does not have cognitive capacity, their proxy or authorized representative can 
withdraw a patient from the study. CRAs cannot withdraw a patient from study.  
Because of the fragile patient population being studied, the patient should not be automatically assumed 
to be withdrawn from the study if they are too ill to complete surveys or if they decline to complete 
surveys or GA procedures at one or more visits or go into hospice.  The CRA should continue to obtain 
medical chart data, as it relates to subject outcomes, treatment and toxicity outcomes (see Section 11.4.1c) 
for both active with missing data and withdrawal patients unless the patient provides in writing that they 
no longer wish this data to be collected. This should be provided to the UR NCORP Research Base.  
These procedures do not require patient participation.  Research Base staff will also obtain Medicare data 
if agreed to in the patient consent.   
All data will be kept in a confidential manner.  All data will be used unless permission is revoked in 
writing and forwarded to the URCC NCORP Research Base.  Site staff should forward any such 
correspondence to the URCC NCORP Research Base. 
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15. STATISTICAL PLAN
15.1. Statistical Considerations 
Unless otherwise stated, all statistical tests will be performed at the two-tailed 5% level of significance.   
Likewise, 95% confidence intervals will be constructed for effect estimates.  Data will be analyzed on an 
"intent-to-treat" basis. The assumptions underlying all statistical analyses will be thoroughly checked 
using appropriate graphical and numerical methods.110,111  In case of serious violations of distributional 
assumptions such as normality, appropriate transformations or nonparametric methods will be 
performed.112,113  If outliers or influential data are detected, the accuracy of the data will be investigated.  
If no errors are found, analyses will be repeated after removing these cases to evaluate their impact on the 
results.  However, the final analyses will include these data points. 
This is a cluster-randomized trial with NCORP practice sites being the clusters.  The analyses involve use 
of mixed models that take into consideration possible correlation among the participants within a cluster.  
This is accomplished by including NCORP site as a random effect in all the models below.  Intra-cluster 
correlation (ICC) will be calculated from the variance component estimates as Var(NCORP) / 
[Var(NCORP) + Var(Residual)].  To estimate uncertainty in the calculated ICCs, we will use Bayesian 
methods (Markov Chain Monte-Carlo) assuming a noninformative prior to estimate credible intervals for 
the computed ICCs.  The specific NCORP differences will be assessed graphically using Best Linear 
Unbiased Predictors (BLUP) of the mean response for each NCORP. 
15.2. Justification of Study Design 
The study is designed as a cluster randomized trial because a care or service model is applied to each 
participant by the oncology team.  If a cluster design were not undertaken, there would be contamination 
in that practitioners and teams could choose the care or service model once they were exposed to 
participants in both arms.  The cluster randomized design will allow for the comparison of toxicity 
between Arms 1 and 2 in the same timeframe.   
15.3. Sample Size Considerations 
Cluster Randomized Design Sample 
Size:  The primary outcome measure 
for this study is the proportion of 
participants that experience grade 3-5 
toxicity within 3 months of treatment 
initiation.  Given the clinical 
significance of toxicity, we propose 
that any statistically significant 
reduction in the proportion of 
participants that experience toxicity 
would be clinically significant.  In the 
published CARG study, 307 of 500 
participants had advanced cancer and of these, 141 (46%) experienced grade 3, 4, or 5 toxicity within 3 
months.5  The proportion of participants that underwent full geriatric assessment plus interventions in our 
geriatric oncology clinic that experienced chemotherapy toxicity was 33%.  Our participant population 
aged 70 and over with advanced solid tumor malignancies receiving chemotherapy, was similar to 
participants studied in our preliminary work.  Our previous multicenter study5 has allowed us to calculate 
the intracluster correlation (ICC) amongst 7 different sites for the assessment of the primary outcome, 
toxicity.  The ICC was low, 0.002, which likely reflects the standard way that oncology physicians and 
their teams assess chemotherapy toxicity with NCI Common Toxicity Criteria.  To be on the conservative 
side, our power calculations assume ICC=0.10.  This design (8 sites per arm and 43 participants per site) 
has 80% power to detect a 13% reduction in the proportion of participants that experience grade 3-5 
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chemotherapy toxicity within 3 months of chemotherapy initiation, assuming a two-sided significance 
level of 0.05 and an ICC of 0.10.  See Table 2 for sample size requirements for some other changes in 
proportion of toxicity.  Accounting for a small drop-out rate of 10% (based on our observational cohort 
data5), the targeted accrual will be 700 participants total.  Because toxicity is assessed from the medical 
record and primary team, the drop-out rate reflects participants that sign consent but withdraw prior to 
baseline assessment.   
During NCORP site recruitment, if more than 16 NCORP sites are interested in participating, we will 
allow randomization. The total participant sample size will remain the same, and accrual will cease 
when that target is met. 
15.4. Primary Analysis 
a.
The primary outcome measure for this study is the proportion of participants that experience
grade 3-5 toxicity within 3 months of treatment initiation.  Because of the cluster randomized
study design, we will apply generalized linear mixed model (GLMM) methodology.114
Toxicity (Yes/No) will be the response, and arm, treatment type and arm:treatment type
interaction will be the fixed effects.  NCORP practice site will be entered as a random effect
independent of residual error.  Estimation will be performed using the Residual Pseudo
Likelihood procedure, assuming a binomial distribution and logit link.  Using the fitted
model, we will provide estimates and 95% confidence intervals for proportion of participants
that experience toxicity for each arm, as well as risk ratios between the arms. This will allow
the results for those who fit the original eligibility criterion (on chemotherapy) to be
compared to the other allowed treatments that have a similar toxicity profile as
chemotherapy.
15.5. Secondary Analyses 
15.5.1. Secondary Aim 1.  We will determine the effect of the intervention on 6-month survival 
using log rank tests and survival plots. Assuming an exponential survival distribution, and given 
survival proportion of 0.89 at 6 months from our previous observational work5 and a sample size of 
624, we estimate that there will be 80% power (0.05 significance level) to detect an increase in 
survival proportion greater than 0.942, implying a detectable hazard ratio of 0.511.   
15.5.2. Secondary Aim 2a.  We will compare the effect of the intervention on measures of 
decisional regret (both participant and oncology physician) using four linear mixed models (regret).  
For each model, Arm will be the fixed effect and NCORP will be a random effect (independent of 
residual error).  Restricted Maximum Likelihood (REML) estimation will be used, and inference will 
be performed using the Kenward-Roger degrees of freedom adjustment procedure.  We will also 
determine whether the intervention influences the relative dose intensity (RDI) of treatment given in 
the first line setting by analyzing the Phase II RDI in the same manner.  In addition, to investigate 
whether the intervention changes dosing, we will analyze with a linear mixed model.  In this model, 
RDI will be the response.  The fixed effect will be Arm and the random effect will be NCORP.  
Overall change in dosing will be assessed with an F Test. Lastly, we will determine the association of 
baseline oncology physician and patient decision-making interaction on likelihood of developing 
toxicity. Variables to be evaluated will be derived from participant assessments (control preferences 
(CP)) and oncology physician comfort (PC) with shared decision-making.  A GLMM will be fit with 
chemotherapy toxicity as the response, Arm, , CP and PC as fixed factors, and NCORP site as a 
random effect independent of residual error.  Otherwise, the modeling methodology is the same as for 
the Primary Aim. 
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15.5.3. Secondary Aim 2b. We will compare whether the uptake of geriatric assessment 
interventions (% of recommended interventions carried out influences chemotherapy toxicity.  The 
data from the intervention arm will be fit to a GLMM with  toxicity as the outcome, percent of 
recommended interventions as the fixed effect, and NCORP site as a random effect independent of 
residual error.  Otherwise, the modeling methodology is the same as for the Primary Aim. 
15.5.4. Exploratory Aims.   We will evaluate changes in functional abilities and physical 
performance between Arms 1 and 2.  For each of these outcomes, a GLMM structured the same as 
that used in Specific Aim 2 will be used.  Functional status will measured with IADL score.   Physical 
performance will be measured with the OARS Physical Health Subscale and the Short Physical 
Performance Battery.  PRO-CTCAE analyses will be performed using descriptive statistics, 
correlations, and regressions to evaluate changes in symptoms over time, relationship between PRO 
results and clinician-related to toxicity, and relationship of symptoms with treatment decisions. 
15.6. Missing Data 
Every effort will be made to encourage and facilitate participants' completion of questionnaires, but 
because of dropout, missing data will occur. We will evaluate the patterns of missing data and 
associations of missingness with other available variables. Under the missing at random (MAR) 
assumption, we will use multiple imputation to obtain unbiased estimates of the key statistics.  If the data 
are suspected to be missing not at random (MNAR), a sensitivity analysis using selection and/or pattern-
mixture models will be run to determine the impact on the results.115  If the estimates are similar to the 
ones obtained from the simpler analysis of only complete cases, we will report the complete-case analysis 
results.  
It is hypothesized that the GA summary and GA-driven recommendations provided in the intervention 
arm will result in a greater number of missing data (e.g., if participants decide not to go onto a new 
treatment regimen after reviewing the summary) so for these participants, no toxicities will be reported. 
We will impute this kind of missing data with the data from the PRO-CTCAE.  We will also still follow 
the participants.  This will enable us to perform ITT analysis.116 Missing data for other reason, e.g., 
dropout, will be handled with the methodologies described in the previous paragraph.   
16. DATA MANAGEMENT AND QUALITY ASSURANCE
16.1. Training Procedures 
A special training session was held at the annual URCC NCORP Research Base meeting in September 
2013. This training included a detailed review of the study rationale, design, and research administration 
procedures. Training sessions will be held with the staff from each site via teleconference and at the 
annual meetings.  These sessions and the corresponding procedures manuals will review the following: 1) 
informed consent; 2) completing the assessments using Teleforms; 3) completing the functional and 
objective measures; 4) data collection via chart extraction; 5) completing the web-based intervention 
using mycarg.org (for intervention arm only); 6) transfer of the data to the URCC NCORP Research 
Base; 7) formulating the research chart; and 8) a discussion of interviewing techniques so that the 
research team will standardize their approaches in order to elicit consistent data from participants. There 
will be a protocol update every year at the annual Research Base meeting.  All assessments, data 
collection forms, and manuals will be readily available on the NCORP Research Base website.  
16.2. Data Management 
The same protocols and procedures for data quality and control that we use for all URCC NCORP 
Research Base protocols (which accrued over 1,000 participants in the previous year) will be used for this 
study. Once the patient consents to the protocol, he/she will be assigned a unique identifier by the 
Research Base, which will be used to link all participant data.  Oncology physician and participant 
assessments will be captured using scannable Teleforms. The CRA and/or Research Nurse at each site 
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will ensure that data are complete prior to submission.  Assessment of cancer characteristics, cancer 
treatment and RDI, and toxicity outcomes will be captured via Teleforms.  At the Research Base, data are 
scanned into an electronic password-secured Access database which is backed up every 24 hours.  At the 
Research Base, staff will ensure that all data are collected in order to minimize missing data by employing 
multi-step verification procedures and querying originating sites for missing or ambiguous data.  Queries 
will be reviewed with the sites, especially regarding the ascertainment of toxicity. 
16.3. REDCap 
Data are also collected and managed by the research teams at University of Rochester Medical Center 
using REDCap electronic data capture tools hosted at URMC.  We will evaluate records, clinical 
characteristics, and outcomes and we will utilize REDCap to collect and manage this information. 
Further, we will link this information to the encrypted ACCESS database (which contains the survey 
information) with a unique identifier.   
16.3.1. The University of Rochester Medical Center provides the following information on the 
REDCap program: “Vanderbilt University, in collaboration with a consortium of institutional 
partners, has developed a software toolset and workflow methodology for electronic collection and 
management of research and clinical trial data, called REDCap (Research Electronic Data Capture). 
The REDCap system is a secure, web-based application that is flexible enough to be used for a 
variety of types of research.  It provides an intuitive interface for users to enter data and real time 
validation rules (with automated data type and range checks) at the time of data entry. REDCap offers 
easy data manipulation with audit trails and functionality for reporting, monitoring and querying 
participant records, as well as an automated export mechanism to common statistical packages (SPSS, 
SAS, Stata, R/S-Plus).  Through the REDCap Consortium, Vanderbilt has disseminated REDCap for 
use around the world. Currently, over 240 academic and non-profit consortium partners on six 
continents with over 26,000 research end-users use REDCap.”  
16.3.2. According to the University of Rochester Clinical and Translational Science Institute 
(CTSI), REDCap is supported with the following means. “The CTSI Informatics Core, a unit of 
the SMD Academic Information Technology (AIT) Group, will serve as a central facilitator for data 
processing and management.  REDCap data collection projects rely on a thorough study-specific data 
dictionary defined in an iterative self-documenting process by all members of the research team, with 
planning assistance from the AIT-CTSI Informatics Core. The iterative development and testing 
process results in a well-planned data collection strategy for individual studies.”  
16.3.3. The CTSI states that regarding security, “REDCap servers are housed in a local data center 
at the University of Rochester and all web-based information transmission is encrypted. REDCap was 
developed in a manner consistent with HIPAA security requirements and is recommended to 
University of Rochester researchers by the URMC Research Privacy Officer and Office for Human 
Subject Protection. 
16.4. Data Storage 
All written materials will be kept confidential, locked in the private offices and limited-access file room 
of the URCC NCORP Research Base and identified by ID numbers.  All electronic information will be 
kept confidential with password-protected, limited access. 
The Case Summary should accompany ALL data submissions.  All completed forms must be submitted 
should be sent within 7 days of study visit to: 
Libby Nagalski 
URCC NCORP Research Base 
Saunders Research Building 
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265 Crittenden Blvd 
Box CU 420658 
Rochester, NY 14642 
17. DATA COLLECTION AND MEASURES
For a detailed description of the measures that will be collected, refer to Appendix IIA-IID:  Summary of 
Measures, Participant Measures, Clinical Research Associate Materials, and Oncology physician 
Measures.  
18. PARTICIPANT CONSENT AND PEER JUDGMENT
All investigational, FDA, NCI, state, federal and institutional regulations concerning informed consent 
and peer judgment will be fulfilled. 
19. RECORD AND DATA RETENTION
Clinical research records are source documents and records, in any form (including, but not limited to, 
written, electronic, magnetic, and optical records, in addition, scans (x-rays and electrocardiograms) that 
describe or record the methods, conduct, and/or results of a trial, and the actions taken. Unlike 
pharmaceutical-sponsored research, under the Terms of the NIH Award, the awardee institution retains 
ownership of the clinical research records that were conducted with NIH support. Records may be 
preserved in hardcopy, electronic or other media form since there is no regulatory requirement that 
clinical research records be retained in a certain type of format. However, investigators should check with 
their institution for institutional policies and procedures pertaining to record retention. All records relating 
to research that is conducted must be retained for at least five years after completion of the research. The 
three-year time period begins when the individual institution’s engagement in the human subject’s 
research activity ends. Human subject research activities are considered completed once all research-
related interventions and interactions with human subjects have been completed, all data collection and 
analysis of identifiable private information described in the IRB-approved research plan have been 
finished and primary analysis of either identifiable private or de-identified information is completed.  
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