EMA Public Consultation on – ‘Points to consider on frailty: Evaluation instruments for baseline characterisation of clinical trial populations’
- Start of public consultation: 21 December 2015
- Deadline for comments: 31 May 2016
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Article 6 of the Clinical Trials Regulation ((EU) No 536/2014) requires a justification for the gender and age allocation of subjects and, if a specific gender or age group is excluded from or underrepresented in the clinical trials, an explanation of the reasons and justification for these exclusion criteria.
Reasons for exclusion often have been poorly justifiable, and have included predefined arbitrary upper age limits, lists of different comorbidities or polypharmacy. Such frequent exclusion has generated a situation of “evidence biased”, as opposed to evidence based medicine for older adults. This selection bias is even more evident for the frail elderly, who account for a large proportion of older persons at risk. Important elements to be considered in the development of a new medicine for use in the older population include the recruitment of sufficient numbers of elderly in appropriate age ranges (particularly the very elderly) for Pharmacokinetics (PK) as well as PK/PD analyses, the use of an age- appropriate measure of renal function, and awareness of and openness to testing covariates reflecting biological rather than chronological age. The very elderly often exhibit enhanced PD sensitivity and thus exploration of the minimum effective dose is key to improving tolerability. Better characterisation of this growing segment of the population, following a standardized approach, might also help the evaluation of efficacy and safety of drugs in the post authorisation phase, and perhaps in defining enrolment criteria for future studies in the pre authorisation phase(1, 2).
- The Agency should perform a search among available documentation and other scientific data to identify available and validated instruments/methods (e.g. scales) which can be used to examine effect and safety in “frail” patients.
- In August 2011 the Committee for Medicinal Products for Human Use (CHMP) requested the GEG (Geriatric Expert Group) to perform such a search, and this Points to Consider document is the result of that work.
A standardized characterisation of frailty is potentially useful for risk stratification and to improve the description of the characteristics of older populations involved in clinical trials. If such frailty scales could be routinely introduced to characterise the baseline demographics of the population enrolled in a clinical trial for a drug with highly prevalent use in the older population, this would enhance the knowledge of the benefit/risk balance of the product in the target population.