Geriatric Investigational Plan - Clinical Trials for Elderly

Every clinical trial should have a protocol and the protocol needs to include the inclusion/exclusio criteria to define the study population (i.e., who can participate in the trial). The first inclusion criterion is usually the age limit. In many clinical trials sponsored by AstraZeneca, the 'Ages Eligible for Study' was defined as "18 Years to 130 Years (Adult, Older Adult)". Here are links to entries in clinicaltrials.gov for two of these studies: NEPTUNE study and MYSTIC study The upper limit of 130 years old for the study triggered me to look into the age range for clinical trials in adult population (especiaily the upper limit in elderly patients).

The clinical trials in the pediatric population and the age groups in the pediatric population have been discussed in previous posts.

• Age Group in Pediatric, Perinatal or Preterm, and Geriatric Subjects
• Pediatric use and geriatric use of drug and biological product

The reason to have an upper limit of age for study participants is to have a homogeneous population for the study to maximize the chance to have a positive study.  Nowadays, many trials do not set an upper limit for age. An 80-85-year-old individual can be very healthy and an 80-85 years old patient can participate in clinical trials without problems.

For pediatric population, in order to obtain the indication or label, a separate set of clinical trials need to be conducted. There are many requirements and rules for pediatric clinical trials. Regulatory agencies encouraged the sponsors to do clinical trials in pediatric population – pediatric investigational plan (PIP).

Similarly, the safety and efficacy of the specific drug product should also be studied in the geriatric population. The safety and efficacy of a product may be different between the geriatric population and the general adult population. There was an ICH E7 STUDIES IN SUPPORT OFSPECIAL POPULATIONS:GERIATRICS and its Questions and Answers. FDA has a guidance on "Content and Format for Geriatric Labeling". Below are some additional discussions about the clinical trials in the geriatric population.

• Disparate Inclusion of Older Adults in Clinical Trials: Priorities and Opportunities for Policy and Practice Change
• Why Do Clinical Trials Need Older and Diverse Participants?
• https://www.fda.gov/downloads/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstotheFDCAct/FDASIA/UCM410474.pdf
• FDA-ASCO Public Workshop: Geriatric Oncology Workshop
• Clinical Discussion of Specific Clinical Discussion of Specific Populations
• GAO 2007 Prescription Drugs: FDA Guidance and Regulations Related to Data on Elderly Persons in Clinical Drug Trials

For a study in adult including elderly patients, the typical criteria for age will be 18 years and older with no upper limit for age. In this way, the geriatric subjects can be enrolled into the study if the subject meets all other inclusion/exclusion criteria and the very older patients can be enrolled into the study if they are healthy enough. However, if we look at the various studies, different sponsors use different criteria for age in their studies.

Using Phase III studies in NSCLC, here are some examples from clinicaltrials.gov. We can see that different clinical trials use different ranges for age. 

Study	Inclusion Criterion for Age
A Study of Nivolumab + Chemotherapy or Nivolumab + Ipilimumab Versus Chemotherapy in Patients With EGFR Mutation, T790M Negative NSCLC Who Have Failed 1L EGFR TKI Therapy (CheckMate722)	18 Years and older (Adult, Older Adult)
Evaluate the Efficacy and Safety of IBI305 in Patients With Advanced or Recurrent Non-squamous NSCLC	18 Years to 70 Years (Adult, Older Adult)
MIL60 Versus Bevacizumab in Patients With Treatment-naïve Non-squamous Non-small Cell Lung Cancer	18 Years to 75 Years (Adult, Older Adult)
A Study Comparing MB02 and Avastin® in Subjects With Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) (STELLA)	18 Years to 80 Years (Adult, Older Adult)
Effect of Tumor Treating Fields (TTFields) (150 kHz) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure (LUNAR)	22 Years and older (Adult, Older Adult)
Study of ONO-4538 in Non-Squamous Non-Small Cell Lung Cancer	20 Years and older (Adult, Older Adult)

Whether or not the upper limit is set to 70, 75, 80 years old or have no upper limit, if the drug is approved, the indication for the drug will be the same and the only difference may be the descriptions in section 8.5 of the drug label per FDA's guidance "Labeling for Human PrescriptionDrug and Biological Products –Implementing the PLR Content and Format Requirements".