Inclusion of Older 
Adults in Cancer 
Clinical Trials 
Guidance for Industry 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
March 2022 
Clinical/Medical 
   
Inclusion of Older 
Adults in Cancer 
Clinical Trials 
Guidance for Industry 
 
 
 
Additional copies are available from: 
 
Office of Communications, Division of Drug Information 
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD  20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: druginfo@fda.hhs.gov 
https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs 
 
and/or 
 
Office of Communication, Outreach, and Development  
Center for Biologics Evaluation and Research 
Food and Drug Administration 
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Silver Spring, MD  20993-0002 
Phone: 800-835-4709 or 240-402-8010; Email: ocod@fda.hhs.gov 
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-information-biologics/biologics-
guidances 
 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Oncology Center of Excellence (OCE) 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
March 2022 
Clinical/Medical 
  Contains Nonbinding Recommendations 
 
TABLE OF CONTENTS 
 
I.  INTRODUCTION ...................................................................................................... 1 
II.  BACKGROUND ........................................................................................................ 2 
III.  RECOMMENDATIONS............................................................................................ 3 
A.  Early Clinical Development ........................................................................................... 4 
B.  Clinical Trials ............................................................................................................... 4 
C.  Postmarket ................................................................................................................... 6 
 
  Contains Nonbinding Recommendations 
Inclusion of Older Adults in Cancer Clinical Trials 
Guidance for Industry1 
 
 
 
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on 
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can 
use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To 
discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the title 
page. 
 
 
 
I.  INTRODUCTION  
 
This guidance provides recommendations regarding the inclusion of older adult patients in 
clinical trials of drugs2 for the treatment of cancer.  For the purpose of this guidance, older adults 
are those 65 years of age and older.  Specifically, this guidance includes recommendations for 
including an adequate representation of older adults in cancer clinical trials to better enable 
evaluation of the benefit-risk profile of cancer drugs in this population.  Most cancer trials do not 
have an upper age limit for exclusion; however, adults 75 years of age and older are 
underrepresented in cancer clinical trials.3  The guidance emphasizes the particular importance of 
including adults 75 years of age and older in cancer clinical trials.  This guidance is intended to 
assist stakeholders, including sponsors and institutional review boards, responsible for the 
development and oversight of cancer clinical trials.  
 
Enrolling an adequate representation of the range of patients in a clinical trial that may be 
exposed to a drug after approval is important.  It provides the ability to understand the drugs 
benefit-risk profile across the patient population likely to use the drug in clinical practice (e.g., to 
identify whether there are differences in the benefits and/or risks of the drug in different 
populations).  Including information in the labeling describing use in older adults may help 
promote the safe and effective use of these products in older adults and better inform treatment 
decisions in clinical practice.4 
 
 
1 This guidance has been prepared by the Oncology Center of Excellence (OCE), Center for Drug Evaluation and 
Research (CDER), and Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration. 
2 For the purposes of this guidance, references to drugs includes drugs approved under section 505 of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 355) and biological products licensed under section 351 of the Public 
Health Service Act (42 U.S.C. 262). 
3 Singh H, Kanapuru B, Smith C, et al., 2017, FDA Analysis of Enrollment of Older Adults in Clinical Trials for 
Cancer Drug Registration: A 10-Year Experience by the U.S. Food and Drug Administration, JCO, 35:15 suppl, 
10009-10009. 
4 See the draft guidance for industry Geriatric Information in Human Prescription Drug and Biological Product 
Labeling (September 2020).  When final this guidance, will represent the FDAs current thinking on this topic. For 
the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
 
  1  Contains Nonbinding Recommendations 
The contents of this document do not have the force and effect of law and are not meant to bind 
the public in any way, unless specifically incorporated into a contract.  This document is 
intended only to provide clarity to the public regarding existing requirements under the law.  
FDA guidance documents, including this guidance, should be viewed only as recommendations, 
unless specific regulatory or statutory requirements are cited.  The use of the word should in 
Agency guidance means that something is suggested or recommended, but not required.  
 
 
II.  BACKGROUND 
 
Adults 65 years of age and older, and especially those 75 years of age and older, are 
underrepresented in cancer clinical trials despite representing a growing segment of the 
population of cancer patients.5,6  Therefore, obtaining more information is important to better 
inform treatment decisions for older adults with cancer.  Cancer is a disease generally associated 
with age, with the number of cancer cases projected to multiply due to a rapidly aging U.S. 
population.7  FDA is engaged with stakeholders to improve the representation of older adults in 
cancer trials. 
 
The issue of older adults being underrepresented in clinical trials persists in oncology despite 
FDAs efforts to increase their inclusion in clinical trials.  FDA has encouraged the inclusion of 
older adults in clinical trials, including through interaction with sponsors and through several 
guidance documents.8,    In addition, FDA published a series of guidances that encourages 
sponsors to broaden cancer clinical trial eligibility criteria to enhance the generalizability of trial 
results and the ability to understand the drugs benefit-risk profile across the patient population 
likely to use the drug in clinical practice.  One guidance in the series, Cancer Clinical Trial 
Eligibility Criteria: Patients with Organ Dysfunction or Prior or Concurrent Malignancies (July 
2020) is particularly relevant to older adults.  This guidance encourages the inclusion of patients 
with organ dysfunction and with prior or concurrent malignancies, as appropriate, to better 
reflect the population that will use the drug in clinical practice.  It also includes specific 
recommendations regarding the inclusion of patients with renal, cardiac, and hepatic dysfunction 
and of patients with prior or concurrent malignancy, all of which may increase with age. 
 
Differences may exist between younger and older adult patients in drug response and toxicity 
due to age-related physiologic changes.  For example, the pharmacokinetics of the drug, or the 
pharmacodynamic response to the drug, or both may vary between younger and older adult 
 
5 Singh H, Kanapuru B, Smith C, et al., 2017, FDA Analysis of Enrollment of Older Adults in Clinical Trials for 
Cancer Drug Registration: A 10-Year Experience by the U.S. Food and Drug Administration, JCO, 35:15 suppl, 
10009-10009. 
6 Smith BD, Smith GL, Hurria A, et al., 2009, Future of Cancer Incidence in the United States: Burdens Upon an 
Aging, Changing Nation, JCO, 27(17): 2758-65. 
7 Levit L, Singh H, Klepin H, Hurria A, 2018, Expanding the Evidence Base in Geriatric Oncology: Action Items 
from an FDA-ASCO Workshop, JNCI, 110(11): djy169. 
8 See the guidance for industry Studies of Drugs Likely to be used in the Elderly (November 1989), E7Studies in 
Support of Special Populations: Geriatrics (August 1994) and E7 Studies in Support of Special Populations: 
Geriatrics Questions and Answers (March 2012) and Enhancing the Diversity of Clinical Trial Populations  
Eligibility Criteria, Enrollment Practices, and Trial Designs (November 2020). 
 
  2  Contains Nonbinding Recommendations 
patients.  In addition, older adults often have comorbidities and may be taking concomitant 
medications that could impact the efficacy of the cancer drug and may also impact the incidence 
and the severity and seriousness of an adverse reaction.  It is important that the spectrum of older 
adults included in clinical trials are representative of the intended population, including those 
with physiological decline (e.g., frailty).  Furthermore, there may be important differences in 
efficacy in older adult patients compared to the younger or general population, and information 
describing such differences should be conveyed to patients and healthcare providers where 
appropriate.   
 
Geriatric (i.e., older adult) use information must be included in labeling, unless clearly 
inapplicable.9  FDAs draft guidance for industry: Geriatric Information in Human Prescription 
Drug and Biological Product Labeling (September 2020)10 assists applicants in determining the 
appropriate placement and content of geriatric information in labeling so that the information is 
clear and accessible to health care practitioners and includes content that guides the safe and 
effective use in geriatric patients.  In addition, FDAs Drug Trials Snapshots11 provides 
consumers with relevant information about the demographic profile of participants in key clinical 
trials that supported the original approval of new molecular entities and new biological products 
since 2015.  Snapshots can also highlight differences, if applicable, in benefits and side effects 
among demographic groups, including, for example, differences based on age when a clinical 
trial includes a representative population of older adults.  Demographic information may also be 
available on FDAs website within the posted product approval information.12   
 
 
III.  RECOMMENDATIONS     
 
Clinical trials should include study populations reflecting the intended population that may 
receive the intervention being evaluated, if approved.  In general, to achieve an unbiased 
estimate of treatment effect in the general population, sponsors should develop a strategy to 
enroll diverse populations, including different age groups, that are consistent with the intended 
use population.  For most cancers, clinical trials should include a representative population of 
older adults.13  Older adults, including those with physiological decline, should be enrolled in all 
phases of clinical trials when they can be safely and ethically enrolled.   
 
Sponsors of cancer trials should consider the expected age range of their target population early 
in development.  CDER and CBER are available to discuss plans for enrollment of older adults 
in cancer clinical trials, particularly when enrollment of adequate representation of older adults 
may be challenging.   
 
 
9 See 21 CFR sections 201.56(d)(4), 201.57(c)(9)(v), and 201.80(f)(10). 
10 When final, this guidance will reperesent the FDAs current thinking on this topic. 
11 Available at https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots 
12 See Drugs@FDA. 
13 One source of data that may be considered when estimating the incidence of a cancer in older adults is the 
National Cancer Institutes Surveillance, Epidemiology, and End Results Program, SEER Incidence database, 
available at https://seer.cancer.gov/data/.  
 
  3  Contains Nonbinding Recommendations 
A strategy regarding inclusion of older adults should include all known information including for 
example, prevalence of the condition, diagnosis and treatment patterns, prior relevant studies, 
and differences in outcomes related to safety or efficacy.  The guidance for industry Enhancing 
the Diversity of Clinical Trial Populations  Eligibility Criteria, Enrollment Practices, and Trial 
Designs (November 2020) includes recommendations for inclusive trial practices, trial design 
and methodological approaches, and other study design and conduct considerations for 
improving enrollment that sponsors should consider regarding older adults.   
 
To understand potential age-related differences that may be relevant to the clinical development 
of a cancer drug, FDA recommends the following: 
 
A.  Early Clinical Development 
 
  Sponsors should enroll older adults, if appropriate, in early phase studies to obtain 
information on safety, exposure, and response to better inform the study design 
and dose selection of later phase studies.   
 
  Sponsors should evaluate drug interactions early in drug development to allow 
enrollment of older adults who may otherwise be excluded because of their 
concomitant medication use.   
 
  Sponsors should document co-morbidities and make every effort to safely include 
these patients as well as those with organ dysfunction and prior/concurrent 
malignancies.14   
 
B.  Clinical Trials 
 
  Trial design  
 
Sponsors should make every effort to enroll a representative population of older 
adults in their pivotal randomized trials.  To facilitate the enrollment of older 
adults in cancer trials, sponsors may consider flexible approaches to trial design, 
such as age-based stratification or analyses based on hypothesized efficacy 
differences in older adults compared to the younger adults participants (65 
years) to allow a focused benefit/risk assessment.  If the pivotal trials are not able 
to enroll a representative sample of older adult patients, alternative trial designs 
should be proposed.  This may include an open-label safety study that can enroll 
and analyze an older adult population separately in a parallel arm of a trial.  
Additional considerations for this particular trial design can be found in the  
guidance for industry Placebos and Blinding in Randomized Controlled Cancer 
Trials for Drug and Biological Products (August 2019).  In some cases, the older 
adult arm(s) can be actively accruing at the time of new drug application (NDA) 
or biologics license application (BLA) or supplement submission.  
 
 
14 See guidance for industry Cancer Clinical Trial Eligibility Criteria: Patients with Organ Dysfunction or Prior or 
Concurrent Malignancies (July 2020).  
  4  Contains Nonbinding Recommendations 
An example of a possible trial design approach is a randomized controlled trial 
that enrolls younger and older adults and stratifies by age.  The intent-to-treat 
(ITT) population consists of all enrolled patients, with the primary study 
hypothesis evaluating effectiveness in randomized patients under 75 years of age.  
Using a hierarchical testing strategy, after the primary analysis in patients under 
75 years of age, subsequent analyses would be done in the ITT population to 
provide safety and efficacy information about all patients.  If the size of the older 
patient population is adequate and powered to address the hypothesis, results in 
the older population can also be analyzed separately.    
 
The design of the development program should reflect any important differences 
in a drugs benefit-risk balance in older adults compared to younger adults.  In the 
design of the clinical development program, we recommend that sponsors 
consider perspectives of older adults, seeking input from patients and advocacy 
groups, as well as input from those caring for older adults such as clinicians and 
caregivers.  This information can inform the design of the clinical trials, such as in 
assuring meaningful endpoints are selected, as well as in the conduct of the trial, 
such as in facilitating enrollment and retention of older adults.15 
 
  Develop recruitment strategies targeted to older adults 
 
Clinical trials do not have an upper age limit for exclusion, however adults 75 
years of age and older, continue to be underrepresented.  FDA encourages 
sponsors and clinical trial cooperative groups to develop strategies to recruit 
patients that are reflective of the intended population.  Possible challenges with 
recruiting older adults that could be mitigated, particularly among patients 75 
years of age and older, include: location of clinical trial sites (e.g., sites in 
community-based settings may be more accessible to older adults than sites 
located in urban academic centers), format (e.g. digital) and content of 
informational material for the trial, caregiver support, accommodations needed for 
impairment (e.g., visual, mobility, etc.), and travel and other logistics.  Where 
feasible, remote monitoring approaches should be considered. 
 
Sponsors should discuss specific goals for enrollment of older adults with clinical 
investigators and keep the clinical trial sites updated on the progress of enrolling 
older adults in the trial.  Sponsors should discuss the importance of enrolling older 
adults during study training provided to the clinical sites.  In addition, sponsors 
should consider getting input on trial design, trial conduct and recruitement 
strategies from geriatricians, geriatric oncologists, social and behavioral scientists 
with expertise in treating older adults.  Additional input from patient 
advocates/navigators should also be sought. 
 
  Consider collecting additional information for older adults 
 
 
15 See guidance for industry Patient-Focused Drug Development: Collecting Comprehensive and Representative 
Input (June 2020).   
  5  Contains Nonbinding Recommendations 
Sponsors should prospectively consider information that should be collected for 
older adults that will be clinically informative and will provide an understanding 
of clinical outcomes in older adults.  For example, in addition to collection of age 
and performance status, elements from geriatric assessment tools (e.g. functional 
status, cognitive function), and a comprehensive assessment of comorbidities 
should be considered during trial design.16  Incorporating a patient reported 
outcome instrument(s) in cancer trials may encourage older adults to participate in 
clinical trials and the information obtained may inform future research.17  
 
  Consider additional strategies in adverse event monitoring and management 
 
Older adult patients experience with adverse events may differ from younger 
patients.  Developing strategies to capture and manage adverse events in older 
patients (e.g., supportive care measures, involvement of geriatric oncologists and 
other health care professionals with expertise in treating older adults) may 
facilitate older patients completing the trial.  
 
  Report more discrete age subgroups 
 
Because outcomes may differ by increasing age group in patients 65 years of age 
and older, sponsors should identify further age subgroups to understand the drugs 
benefits and risks.18  For example, subgroups such as age 65 years to 74 years of 
age and 75 years of age and older may be relevant.  A particular need exists for 
information in patients 75 years of age and older.  Sponsors may consider 
combining data across trials of similar design to ensure adequate representation of 
older adults across discrete age subgroups.  Reporting clinical trial data from 
older adults in a more standardized and granular way can be more clinically 
useful19.  FDAs guidance for industry Integrated Summary of Effectiveness 
(October 2015) includes recommendations regarding subpopulation assessment 
and reporting in the NDA or BLA that are applicable to subgroups of older adults 
in cancer trials (see section III.D of that guidance).  
 
C.  Postmarket 
 
  Ideally, adequate information on older adults should be captured in the premarket 
clinical trials.  However, if older adults are not adequately represented in pre-
market clinical trials, it may be appropriate to develop a plan to collect data on 
older adults in the postmarket setting.  This could be accomplished with post-
marketing trials examining a broader population, or through collection of real 
 
16 Singh H, Beaver JA, Kim G, Pazdur R, 2016, Enrollment of Older Adults on Oncology Trials: An FDA 
Perspective, JGO, 8: 149-50. 
17 See the guidance for industry Patient-Reported Outcome Measures: Use in Medical Product Development to 
Support Labeling Claims (December 2009). 
18 See the guidance for industry E7 Studies in Support of Special Populations: Geriatrics Questions and Answers 
(March 2012). 
19 See footnote 16. 
  6  Contains Nonbinding Recommendations 
world data in an observational study or registry.  In certain situations, FDA may 
require postmarket studies and clinical trials.20  Sponsors should prospectively 
discuss their plan for collecting additional information in the postmarket setting 
with the CDER or CBER review division or office.  Postmarket data may provide 
clinically useful information, that when appropriate, can be added to the Geriatric 
Use subsection of the labeling or other parts of the labeling.21      
 
20 See section 505(o)(3)(B) of the FD&C Act and draft guidance for industry Postmarketing Studies and Clinical 
Trials-Implementation of 505(o)(3) of the Federal Food, Drug and Cosmetic Act (October 2019). When final, this 
guidance will represent the FDAs current thinking on this topic   
21 See draft guidance for industry:  Geriatric Information in Human Prescription Drug and Biological Product 
Labeling (September 2020).  When final this guidance, will represent the FDAs current thinking on this topic. 
 
  7