ICH E7 guideline on Geriatrics population.pptx

The ICH E7 guideline, titled Studies in Support of Special Populations: Geriatrics, provides recommendations for including elderly patients in clinical trials for new medicinal products. The core purpose is to ensure that the safety and efficacy of drugs are adequately evaluated in the aging population.

1. ICH E7 Guideline Studies in support of special population : Geriatrics -Aaditi Kamble. Assistant Professor (Drug Regulatory Affairs Department)

2. Contents :- Document History Statement of Purpose Principle Scope of Guidance Definition of Population Clinical Experience Pharmacokinetic studies a) Formal Pharmacokinetic studies b) Pharmacokinetic screening approach Pharmacokinetics in Renally or Hepatically Impaired Patients Pharmacodynamic/Dose Response Studies Drug-Drug Interaction Studies

3. Document History :- Dated on 16 September 1992 Codification – E7 Approval by the Steering Committee under Step 2 and release for public consultation. Dated on 24 June 1993 Codification E7 Approval by the Steering Committee under Step 4 R ecommended for adoption to the regulatory bodies of the European Union, Japan and USA.

4. Statement of Purpose:- Purpose of guidance is that clinical testing program should carried out according to harmonised guidelines to ensure development of valuable innovative drugs is achieved with maximum efficacy. In Geriatrics – special consideration required due to underlying diseases, concomitant drug therapy and consequent risk of drug interaction. Principle:- Drug should studied in all age groups including elderly patients of specific age groups which population will later treated by that drug.

5. Scope of Guidance :- New molecular entities – Disease of aging (Alzheimer’s disease) Common disease in Geriatrics (Hypertension) New Formulation and New Combinations New use of previously found drugs Definition of Population:- Patients aged 65 or older. To seek patients in older age range – 75 and above Not to include upper age cut-offs Not to exclude patients with concomitant illness ; drug-disease interaction and drug-drug interaction can be detected.

6. Clinical Experience :- Elderly should include in phase 3 database ( Phase 2 at sponsor’s option ) Geriatric data can come from all phases or from phase 3 or from phase 2/3 or from studies exclusively conducted in geriatric patients. Inclusion of both group studies gives advantage of comparison in younger and older age patients data depending on age related basis. Geriatric population represents sufficiently to permit comparison of drug response to younger patients. Drugs used for diseases in elderly allows detection of clinically important differences than youngers. Disease characterised with aging (Alzheimer’s disease); its treatment expected that geriatric patient will contribute major part of clinical database. Drugs to treat uncommon diseases, smaller number of elderly expected.

7. Pharmacokinetic Studies :- Important differences in younger and older patients recognised through pharmacokinetic differences; related to impairment of excretory functions or drug-drug interaction. Information regarding age-related differences can come at sponsor’s option; either of below ways – Formal Pharmacokinetic Studies Pharmacokinetic Screen Approach A. Formal Pharmacokinetic Studies :- Formal Pharmacokinetic Studies can be done by two ways – In healthy geriatric patients In patients with diseases

8. Initial PK studies can be – Pilot trial of limited size conducted under steady state conditions for sizable differences in older and younger patients or subjects, A larger single dose PK study of sufficient size to permit statistical comparison between younger and older patients or subjects PK profile is also acceptable In either of both case, if large age related differences are found initial PK study need to be followed by multiple dose PK study of sufficient size to permit statistical comparison at steady state condition. B. Pharmacokinetic Screening Approach :- Sponsor can conduct PK evaluation with main phase 3 instead of conducting separate PK evaluation for elderly. This screening procedure involves small number of drug blood level determinations at defined time in phase 2/3 from sufficient patient number under steady state condition to detect age associated differences in PK studies Small differences are also of large medical importance.

9. Pharmacokinetics in Renally or Hepatically Impaired Patients :- Renal impairment can also occur in younger patients General principle of guidance is that , drug excreted through renal mechanism should be studied to detect effects of altered renal function for their PK. Pharmacodynamic/Dose Response Studies :- The number of age related PD differences are too small till date ; therefore separate studies are recommended in following conditions, For sedative, hypnotics and psychoactive drugs and drugs giving CNS effects. Subgroup comparison ( younger vs older) in phase 2/3 clinical trial database indicates differences in drug’s effectiveness or adverse reaction profile which is not explainable by PK studies

10. Drug-Drug Interaction Studies :- Study is important to geriatric patients who uses concomitant medication. General principle is cases where therapeutic range of concomitant drugs is narrow and therapy is great in that case drug-drug interaction studies are considered. Examples :- Digoxin and oral anticoagulant interaction studies; because many drugs alters serum concentration of these drugs while these have narrow therapeutic range and these are widely used in elderly Drugs that undergo extensive hepatic metabolism; determination of effect of hepatic enzyme inducers (phenobarbital) and inhibitors (cimetidine) Drugs metabolised by cytochrome P-450 enzymes.

11. Reference :- https://database.ich.org/sites/default/files/E7_Guideline.pdf https://database.ich.org/sites/default/files/E7_Q%26As_Concept_Paper.pdf