Rational use of medicines in older adults: Can we do better during clinical development?

Saeed, M. A.; Vlasakakis, Georgios; Pasqua, Oscar Della

doi:10.1002/cpt.87

Cited by 7 publications

(9 citation statements)

References 5 publications

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“…25,26 PD changes have also been reported. 27 Characteristics associated with frailty such as sarcopenia and the increased prevalence of comorbidities and polypharmacy also increase the potential for drug-drug interactions 5 and other adverse drug reactions in older relative to younger adults. 25 Factors with the potential to alter the PK or PD of many drugs have been extensively reviewed and include characteristics summarised in Table 1 for PK and Table S1 22,[28][29][30] as indicated for the simvastatin example in Figure 3.…”

Section: Agementioning

confidence: 99%

“…Clearly, alternative and complementary methods are required to ensure the impact of age on treatment response and dose rationale for these patients is accurately characterised. 27 Above all, the safety of clinical trial participants must be the primary concern of sponsors and academic investigators, although this objective should be balanced against the ethical need for clinical trials to provide information of relevance for the frail and elderly patients who will ultimately receive the new medicines developed. Despite the challenges involved, there is evidence to suggest that careful selection of inclusion criteria and judicious, rather than arbitrary, selection of exclusion criteria related to organ function, concomitant therapies and comorbid conditions, can increase the proportion of older participants enrolled in trials without compromising safety.…”

Section: Agementioning

confidence: 99%

“…renal function) and body composition, declining homeostatic reserve, and comorbid diseases contribute to changes in PK with advancing age 25,26 . PD changes have also been reported 27 . Characteristics associated with frailty such as sarcopenia and the increased prevalence of comorbidities and polypharmacy also increase the potential for drug–drug interactions 5 and other adverse drug reactions in older relative to younger adults 25 .…”

Section: The Science Behind the Inclusion Of Diverse Populationsmentioning

confidence: 99%

“…The results of studies in the healthy elderly may not be generalisable to the frail or those with multiple comorbidities and taking numerous medications. Clearly, alternative and complementary methods are required to ensure the impact of age on treatment response and dose rationale for these patients is accurately characterised 27 …”

Section: The Science Behind the Inclusion Of Diverse Populationsmentioning

confidence: 99%

“…From a scientific perspective, decisions on the target population required to attain diversity targets in a Phase 3 MRCT can also be informed by the knowledge of factors identified in early phase trials to influence PK and PD and in turn the potential to pool results in prespecified populations 2. This approach should be complemented by quantitative clinical pharmacology methods, which can be used to explore the implications of baseline clinical and demographic characteristics on the PK, PD, safety and efficacy of new molecules 27. The challenge to ensure adequate representation remains a clinical and scientific rather than a regulatory endeavour.…”

mentioning

confidence: 99%

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Clinical trial diversity: An opportunity for improved insight into the determinants of variability in drug response

Gross

Harry

Clifton

et al. 2022

Brit J Clinical Pharma

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Although the number of countries participating in pivotal trials submitted to enable drug registration has nearly doubled over the past 25 years, there has not been a substantial increase in the diversity of clinical trial populations. In parallel, our understanding of factors that influence medicine response and variability has continued to evolve. The notion of intrinsic and extrinsic sources of variability has been embedded into different regulatory guidelines, including the recent guideline on the importance of enhancing the diversity of clinical trial populations.In addition to presenting the clinical and scientific reasons for ensuring that clinical trial populations represent the demographics of patient populations, this overview outlines the efforts of regulatory agencies, patient advocacy groups and clinical researchers to attain this goal through strategies to meet representation in recruitment targets and broaden eligibility criteria. Despite these efforts, challenges to participation in clinical trials remain, and certain groups continue to be underrepresented in development programmes. These challenges are amplified when the representativeness of specific groups may vary across countries and regions in a global clinical programme.Whilst enhanced trial diversity is a critical step towards ensuring that results will be representative of patient populations, a concerted effort is required to characterise further the factors influencing interindividual and regional differences in response for global populations. Quantitative clinical pharmacology principles should be applied to allow extrapolation of data across groups or regions as well as provide insight into the effect of patient‐specific characteristics on a medicine's dose rationale and efficacy and safety profiles.

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