CoChat
Sign Up
Cited by 160Pharmaceutical Practices and Patient OutcomesPharmaceutical studies and practicesEthics in Clinical Research

Underrepresentation of the Elderly in Clinical Trials, Time for Action

Open access
van Marum, Rob J.·2020·British Journal of Clinical Pharmacology
DOI 10.1111/bcp.14539PMC PMC7495271
Open this paper in CoChat — free accountOpen PDF

Abstract

In the general population, the use of prescription drugs increases with age. European data show that 46% of the European population in the age group 45–54 years use prescribed medicines. This number increases to 87.1% in those aged ≥75 years.1 Due to pharmacokinetic and pharmacodynamic changes with aging, the presence of multimorbidity, and an increased prevalence of drug–drug and drug–disease interactions, this high drug consumption in older people is accompanied by an increased susceptibility to adverse drug events (ADEs).2, 3 This is particularly the case for the subgroup of elderly drug users considered frail, a clinically recognizable state in which the ability of the elderly population to cope with every day or acute stressors is compromised by an increased vulnerability brought by an age-associated decline in physiological reserve and function across multiple organ systems.4 Around 10% of people aged over 65 years are considered frail, rising to between a quarter and a half of those aged over 85.5 Frailty is more prevalent in elderly patients with polypharmacy and especially hyperpolypharmacy (>10 drugs used).6 In the frail elderly population, even small changes in health can have life-changing consequences. An increased susceptibility to hypotensive or sedative effects of drugs may lead to falls, fractures, and a loss of independence, forcing the patient to leave home and move to a nursing home. The same serious consequences can be found in cases of drug induced cognitive deterioration/delirium and incontinence.3 The presence of so-called competing risks challenges the efficacy figures found in standard drug trials.7 Assessing whether a drug is safe and effective for use by elderly persons requires that a sufficient number of elderly persons be included in clinical drug trials. When elderly people are excluded the safety concerns and effectiveness outcomes unique to this population will not be detected making risk: benefit difficult to gauge. In 1993, the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) published the ICH-E7 guideline: "Studies in Support of Special Populations: Geriatrics."8 This guideline, which was adopted by the European Medicines Agency (EMA), the US Food and Drug Administration (FDA) and pharmaceutical companies, states that, as a general principle "Drugs should be studied in all age groups, including the elderly, for which they will have significant utility. Patients entering clinical trials should be reasonably representative of the population that will be later treated by the drug." It also states that "It is important not to exclude unnecessarily patients with concomitant illnesses; it is only by observing such patients that drug-disease interactions can be detected." The guideline defines the geriatric population as comprising patients aged 65 years or more. Regarding the proportion of older persons, it states that "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 fact that the ICH-E7 guideline was published in 1993, one would expect that randomised controlled drug trials nowadays are designed in accordance with this guideline. However, this is not the case. In 2014, Beers et al. studied the inclusion of older people in clinical trials for recently registered drugs.9 They found that in trials involving diseases characteristically associated with ageing, 57% of the included patients were aged 65 and older and 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. Last year, Ruiter et al. published a structured review of approval documents of FDA-approved drugs.10 This review included the 10 most frequently on-label prescribed drug classes, drugs with known pharmacokinetic differences in the elderly or drugs that are relatively contraindicated in elderly patients. Over time, the availability of information regarding the elderly population in these approval documents increased from 0% in the period 1970–1979 to 76% for the period 2010–2018. For most of the drugs (62%), the initial approval documents in the database showed information on pharmacokinetics in an elderly subpopulation. Information on safety and efficacy was less frequently present, that is, 42% and 45%, respectively, and did not improve over time. Major reasons for the underrepresentation of elderly patients in drug trials are the use of arbitrary age limits and exclusion criteria for conditions highly prevalent in the elderly. Cruz-Jentoft et al. studied the World Health Organization (WHO) Clinical Trials Registry Platform for ongoing clinical trials about type 2 diabetes mellitus.11 Of 440 eligible trials, 65.7% excluded individuals using an arbitrary upper age limit. Exclusion for comorbidity was present in 76.8%. Exclusion for polypharmacy (29.5% o

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1111/bcp.14539

Cites

11 of 11 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The use of only healthy older adults creates a knowledge gap that underrepresents older adults with comorbidities.

    “This creates a knowledge gap, which underrepresents those older adults with comorbidities [45].”

    From Smart Speakers for Health and Well-Being of Older Adults: A Mixed-Methods Review (2025) · cites this paper as [45]

    The main text reports that older adults are underrepresented in drug trials, that efficacy and harms data are often missing, and that exclusion criteria for conditions prevalent in older people are a major reason. It specifically describes exclusions for comorbidities. It does not say trials use only healthy older adults; that absolute wording overstates the evidence. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
van Marum, R. J.
Affiliations
Department of General Practice and Elderly Care Medicine, Amsterdam Public Health Research Institute Amsterdam UMC, location VUmc Amsterdam The Netherlands
ORCID
van Marum, Rob J.
Venue
British Journal of Clinical Pharmacology
Publisher
Wiley
Published
2020-09-09
Volume
86
Issue
10
Pages
2014-2016
ISSN
  • 0306-5251 (ISSN-L)
  • 1365-2125
DOI
10.1111/bcp.14539
PMC
PMC7495271
OpenAlex
W3084236582
Cited by
159
References
11
Citations by year
2026: 27 · 2025: 46 · 2024: 28 · 2023: 21 · 2022: 22 · 2021: 13 · 2020: 2
Type
journal article
Language
en
Open access
Licence
Locations
  • British Journal of Clinical Pharmacology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
  • Pure Amsterdam UMC (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ethics in Clinical Research
Keywords
clinical trial participation, frailty, hyperpolypharmacy, adverse drug reactions, drug safety in older adults, competing risks, falls and fractures, nursing home admission, multimorbidity
MeSH terms
Age Factors, Aged, Humans, Patient Selection

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review