Guidance for Industry 

 
E7 Studies in Support of 

Special Populations: 

Geriatrics 

 
Questions and Answers 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

 
February 2012 

ICH 

 
   
Guidance for Industry 

 
E7 Studies in Support of 

Special Populations: 

Geriatrics 

 
Questions and Answers 
 
 
 
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http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm    
 
 
U.S. Department of Health and Human Services 

Food and Drug Administration 

Center for Drug Evaluation and Research (CDER) 

Center for Biologics Evaluation and Research (CBER) 

 
February 2012 

ICH 

 
   
 
TABLE OF CONTENTS 

 
 
 
I.   INTRODUCTION............................................................................................................. 1 
 
II.   QUESTIONS AND ANSWERS....................................................................................... 2 
 
  i  Contains Nonbinding Recommendations  
1
 
Guidance for Industry  
 
E7 Studies in Support of Special Populations:  Geriatrics 

 
Questions and Answers 

 
 
 
 
This guidance represents the Food and Drug Administrations (FDAs) current thinking on this topic.  It 
does not create or confer any rights for or on any  person and does not operate to bind FDA or the public.  
You can use an alternative approach if the approach satisfies the requirements of the applicable statutes 
and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for 
implementing this guidance.  If you cannot identify the appropriate FDA staff, call the appropriate 
number listed on the title page of this guidance.  
 
 
 
 
 
I.  INTRODUCTION  
 
The ICH guidance E7 Studies in Support of Special Populations: Geriatrics provides 
recommendations on special considerations that apply in the design and conduct of clinical trials 
of medicines that are likely to have significant use in the elderly.  Since the E7 guidance was 
made final, experiences implementing the guidance in the ICH regions have given rise to 
requests for clarification. This question and answer (Q&A) document is intended to clarify key 
issues. 
 
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and should 
be viewed only as recommendations, unless specific regulatory or statutory requirements are 
cited. The use of the word should in Agency guidances means that something is suggested or 
recommended, but not required.  
 
 
                                                 
1  This guidance  was developed within the Efficacy Working Group of the International Conference on 
Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) and has been  
subject to consultation  by the regulatory parties, in accordance with the ICH process.  The Q&As in this document 
have been endorsed  by the ICH Steering Committee at  Step 4  of the ICH  process, July 2010.   At  Step 4 of the 
process, the final draft is recommended for adoption to the regulatory  bodies of the European Union, Japan, and the  
United States. 
  1
  Contains Nonbinding Recommendations  
II. 	 QUESTIONS AND ANSWERS 
 
Q1: 	 Why do we need an adequate representation of geriatric patients in the clinical 
database? 
 
A1: 	 Geriatric patients can respond differently from younger patients to drug therapy in a 
number of ways, and such differences can be greater in patients 75 years and older:  
 
(a) The geriatric population has age-related physiological changes that can affect the 
pharmacokinetics of the drug and the pharmacodynamic response to the drug, both of 
which can influence the drug-response and the dose response relationship. 
 
(b) Geriatric patients are more prone to adverse effects since they often have co-
morbidities and are taking concomitant therapies that could interact with the 
investigational drug. The adverse effects can be more severe, or less tolerated, and have 
more serious consequences than in the nongeriatric population. 
 
With the increasing size of the geriatric population (including patients 75 and older) and 
in view of the recent advances in pharmacokinetics and pharmacodynamics since the 
ICH E7 guidance was established in 1993, the importance of geriatric data (from the 
entire spectrum of the geriatric patient population) in a drug evaluation program has 
increased. 
 
Not all potential differences in pharmacokinetics, pharmacodynamics, disease-drug 
interactions, drug-drug interactions, and clinical response that can occur in the geriatric 
population can be predicted from nongeriatric populations, as the geriatric patients are 
far more likely to have multiple illnesses and to be receiving multiple drugs. Therefore, 
to assess the benefit/risk balance of a drug that will be used in the geriatric population, 
these patients should be appropriately represented in clinical trials. 
 
Q2: 	 What should be taken into account when estimating an adequate representation of 
geriatric patients to be included in the clinical database? 
 
A2: 	 It is very important to ensure, to the extent possible, that the population included in the 
clinical development program is representative of the target patient population. As stated 
in the current ICH E7 guidance, estimates of the prevalence of the disease to be treated 
by age or examination of the age distribution of usage for other drugs of the same class 
or for the same indication should be provided by the applicant. This will indicate the 
expected use of the drug and should influence the number of geriatric patients to be 
included in the marketing application. 
 
The current guidance states, for drugs used in diseases not unique to, but present in, the 
elderly, a minimum of 100 patients would usually allow detection of clinically important 
differences. Given the increasing prevalence and the growing recognition of the 
  2
  Contains Nonbinding Recommendations  
complexity of the geriatric population, including concomitant therapies and co-
morbidities, it would usually be appropriate to include more than 100 geriatric patients 
in the phase 2 and 3 databases and include patients over the entire spectrum of the 
geriatric patient population. 
 
In the marketing application, depending on the numbers of patients, data should be 
presented for various age groups (for example <65, 65-74, 75-84, and > 85) to assess the 
consistency of the treatment effect and safety profile in these patients with the 
nongeriatric patient population. 
As single trials may not have sufficient numbers of geriatric patients to allow such 
analyses, these will often need to be carried out on pooled data. Any such analyses will 
need to consider consistency across studies. 
 
Q3: 	 Are there any special patient populations or characteristics that are particularly 
important to address in the planning of the clinical development program? 
 
A3: 	 Geriatric patients often have co-morbidities and concomitant therapies that could 
interact with the investigational drug and make patients more likely to have undesirable 
effects and interactions. Therefore, it is important to assess the safety and efficacy of a 
drug in such patients and to design a study with inclusion/exclusion criteria that allow 
their participation. There may exist a reluctance to include vulnerable geriatric patients 
at high risk of adverse outcomes (so-called frail geriatric patients). However, care in 
randomization should allow the appropriate attribution of findings either to the 
investigational drug or to other factors. 
 
This applies both to drugs intended for the geriatric patient population and for drugs 
used in diseases present in, but not unique to, the geriatric population. 
 
 
Q4: 	 What should be considered for the clinical development program to adequately 
characterize the safety and efficacy of a drug for a marketing application? 
  
A4: 	 An appropriate representation of the geriatric population (including patients with 
concomitant therapies and co-morbidities) should be enrolled in the clinical 
development program to adequately characterize efficacy and safety in the geriatric 
population and allow for comparisons with the nongeriatric population. This information 
would ordinarily be expected in a marketing application. 
 
 In general, it is preferable to include both nongeriatric and geriatric patients in the same 
study(ies), which can facilitate observation of age-related differences. In some cases, a 
separate study in the geriatric population can be preferable.   
 
Every effort should be made to include geriatric patients using concomitant therapies 
and with co-morbidities in the premarketing clinical development program. In some  
  3
  Contains Nonbinding Recommendations  
cases, enrollment of these patients can be challenging and it could be appropriate to 
collect data postmarketing. However, the adequacy of, and the need for, data in these 
patients should be considered during drug development and discussed in the marketing 
application submission. Where enrollment of geriatric patients has been insufficient 
despite the efforts of the applicant, a specific plan to collect data postmarketing should 
be discussed during development and presented in the marketing application.  
 
Information relevant to the geriatric patient population, including any limitations, should 
be reflected in the product labeling. 
 
 
Q5: 	 Are there concerns related to the data specific to the geriatric population that could be 
considered in the planning of the clinical studies? 
 
A5: 	 Depending on the mechanism of action of the drug and/or the characteristics of the disease, 
certain specific adverse events and age-related efficacy endpoints should be actively sought in  
the geriatric population, e.g., effects on cognitive function, balance and falls, urinary  
incontinence or retention, weight loss, and sarcopenia. This may require specific testing, e.g., for 
cognitive function. Applicants should also refer to disease specific guidances for specific 
recommendations concerning the evaluation of both efficacy and safety in geriatric patients. 
 
 
Q6: 	 In light of recent advances in the field of pharmacokinetics and assessment of drug-
drug interactions since the ICH E7 guidance was established, what studies should be 
considered when developing a drug that will be used in geriatric patients? 
 
A6: 	 The pharmacokinetics in geriatric patients (over the entire spectrum of the geriatric 
patient population) should be evaluated to identify age-related differences that are not 
explained by other factors such as reduced renal function or weight differences. The 
potential influence of impaired renal/hepatic function, as well as potential drug 
interactions, is often assessed in studies with nongeriatric subjects. 
 
Population pharmacokinetic analysis could provide the requested data if a sufficient 
number of patients in different age ranges (including patients >65 and >75 years) are 
included in the clinical trials. The applicability of population pharmacokinetics is 
dependent on several factors, e.g. the representation of the target population, the 
pharmacokinetics of the drug, dosing regimens, and analytical requirements. 
 
A specific pharmacokinetic study comparing nongeriatric and geriatric subjects in the 
same study (matched for relevant covariates, e.g., weight, sex) could achieve the same  
goals. 
  
More details on the pharmacokinetic approach (population pharmacokinetics, the 
appropriate design of a specific pharmacokinetic study) and assessment of drug-drug 
interactions can be discussed with the regulatory agencies. 
  4