Erna Beers

Objectives: To investigate the inclusion of older people in clinical trials of recently authorized medicines, evaluating adherence to the 20‐year‐old International Conference of Harmonisation ( ICH ) guideline on geriatrics (E7). Design: Observational. Setting: European public assessment reports, published clinical trials, World Health Organization International Clinical Trials Registry Platform. Participants: Individuals aged 65 and older and 75 and older. Measurements: Number and proportion of randomized participants and all exclusion criteria of studies involving diseases characteristically associated with aging (venous thromboembolism, osteoporosis, atrial fibrillation) and diseases not unique to older adults (type 2 diabetes mellitus, depression, bipolar disorder, epilepsy). Results: In 114 Phase II and III trials of 12 medicines, 43.1% of participants were aged 65 and older, and 16.1% were aged 75 and older. In trials involving diseases characteristically associated with ageing, 57% were aged 65 and older; 22% were aged 75 and older. In trials involving diseases not unique to old age, 9% were aged 65 and older, and 1% were aged 75 and older. Upper age limits were applied in 30.7% of the trials; the frequency did not differ between larger (sample size ≥500) and smaller trials ( P = .36), although it was significantly lower in trials involving diseases characteristically associated with aging (18.0%) than in trials of diseases not unique to old age (45.3%; P = .002). Age‐sensitive exclusion criteria, based on comorbidity (75.4%), concomitant medication (71.9%), and other criteria correlated with age (60.5%) were applied more frequently in larger trials ( P < .02). Conclusion: Studies of diseases not uniquely associated with old age included an unacceptably low proportion of older people, contrary to the recommendations of the ICH E7 guideline. Although the proportion of older participants in trials of diseases characteristically associated with aging was appropriate for certain medicines, the use of age‐sensitive exclusion criteria limits the representativeness of the trial population for daily practice.

The ICH E7 guideline intends to improve the knowledge about medicines in geriatric patients. As a legislative document, it might not reflect the needs of healthcare professionals. This study investigated what information healthcare professionals, regulatory agencies and pharmaceutical industries consider necessary for rational drug prescribing to older individuals. A 29-item-questionnaire was composed, considering the representation in trials, pharmacokinetics, efficacy, safety, and convenience of use in older individuals, with space for additions. Forty-three European professionals with an interest in medication for older individuals were included. In order to investigate their relevance, five items were included in a second questionnaire, with 11 control items. Median scores, differences between clinical and non-clinical respondents and response consistency were analysed. Consistency was present in 10 control items. Therefore, all items of the first questionnaire and the five additional items were analysed. Thirty-seven (86%) respondents returned the first questionnaire; 31/37 (84%) the second. Information about age-related differences in adverse events, locomotor effects, drug-disease interactions, dosing instructions, and information about the proportion of included 65+ patients was considered necessary by most respondents. Clinicians considered information significantly more important than the non-clinical respondents about the inclusion of 75+, time-until-benefit in older people, anticholinergic effects, drug-disease interactions, and convenience of use. Main study limitations are the focus on information for daily practice, while the ICH E7 guideline is a legislative document focused on market approval of a new medicine. Also, a questionnaire with a Likert scale has its limitations; this was addressed by providing space for comments. This study reveals that items considered necessary are currently not included in the ICH E7 guideline. Also, clinicians’ and non-clinicians’ opinions differed significantly in 15% of the items. Therefore, all stakeholders should collaborate to improve the availability of information for the rational prescribing to older individuals.

Background Historically, older patients have been frequently excluded from clinical trials. This has a knock-on effect on the availability of relevant information from trials for health-care professionals prescribing medicines to older individuals in daily clinical practice. Objective To investigate the availability of information relevant to appropriate prescribing for older people in the summaries of product characteristics (SmPCs) of recently approved medicines. Methods An analysis was undertaken of the SmPCs and European public assessment reports (EPARs) of all non-generic medicines indicated for diseases that are common in older individuals and that were approved by the European Medicines Agency between January 2008 and December 2010. The EPARs were considered the second most complete, publicly available document after the pre-authorization dossier. The availability of information was evaluated for 19 items on the representation of and clinical experience in older people, as well as pharmacokinetic and drug–drug interaction studies. These items were derived from the ICH E7 guideline for studies involving geriatric populations in the SmPCs and EPARs. Information not included was classified as being essential or non-essential, based on the product characteristics. Results Fifty-three medicines were investigated. Overall, information on the ICH E7 items was available in 56 % of the SmPCs (EPARs 79 %); 41 % of the SmPCs (EPARs 24 %) did not provide information that should have been included. Twenty-seven percent of the SmPCs, but 78 % of the EPARs, provided information about the number of patients included. Moreover, 2 % of the SmPCs (EPARs 51 %) provided information about the exclusion of patients with common comorbidities, and 14 % of the SmPCs, but 81 % of the EPARs, provided information about exclusion based on age. Conclusions SmPCs, unlike EPARs, do not sufficiently provide adequate information about older individuals. Consequently, it is not clear whether the information about efficacy and safety applies to the frail older patients often seen in daily practice. The SmPC is intended for use by health-care professionals in daily clinical practice and provides basic information for safe and effective prescribing. As the EPAR describes regulatory considerations relevant to drug approval and is too long for daily use, the information about older individuals included in the SmPCs should be improved.