It is well recognised, that the European population is
becoming increasingly aged and for many of these people the
drugs used have not been specifically evaluated in this
population. This document provides recommendations on
ethical aspects of clinical trials performed in older people, who
may in some cases be considered a vulnerable patient
Older people experience a higher incidence of disease-
related morbidities, take more medicines with multiple
medication regimes and account for more adverse drug related
events than their younger counterparts. Thus, it is important to
conduct more research and clinical trials in this patient
population to further the understanding and management of
their conditions and treatment. Medicines used by older people
should be of high quality, appropriately researched and
evaluated throughout their life cycles. The population included
should be representative of the future consumers of the tested
History and rationale for the development of these guidance:
This document is based on several workshops organised by the
EFGCP GMWP, which invited J-M. Vetel and F. Hirsch to
present a first draft based on the European Medicines Agency
(EMA) pædiatrics guideline with the goal to foster ethical
research in this neglected area.
The overall principles and key elements of this guidance
were further elaborated discussed and revised by the GMWP in
the following years and presented at the EMA workshop on
Medicines for Older People in March 2012. Following public
consultation, the GMWP has received many thoughtful
comments from academia, investigators, regulators, patients
advocacy groups and the pharmaceutical industry and has met
twice to review and incorporate as many comments as possible
into the final text. The group has shared it with all those who
had contributed and/or reviewed the draft to inform them and
seek their permission to mention their names.
GUIDANCE SYNTHESIS. MEDICAL RESEARCH FOR AND WITH OLDER
PEOPLE IN EUROPE: PROPOSED ETHICAL GUIDANCE FOR GOOD CLINICAL
PRACTICE: ETHICAL CONSIDERATIONS
L. DIENER1,2, L. HUGONOT-DIENER1,3, S. ALVINO1,4, J.P. BAEYENS1,5, M.F. BONE1,6, D. CHIRITA1,7,
J.M. HUSSON1,8, M. MAMAN1,9, F. PIETTE1,10, A. TINKER1,11, F. VON RAISON1,9
1. European Forum for Good Clinical Practice Geriatric Medicine Working Party (EFGCP GMWP) ; Square de Meeûs – Rue de l’industrie 4. 1000 Brussels, Belgium; 2. REGATES,
Paris, France; 3. AP-HP, groupe hospitalier Paris-centre. Broca Hospital, Department of Geriatrics, 54-56 rue Pascal, 75013 Paris, France; 4. inVentiv Health Clinical, Milan, Italy;
5. University of Luxembourg; 6. South Tyneside NHS Foundation Trust, UK; 7. Grünenthal, Aachen, Germany; 8. Paris, France (+ in 2011); 9. Novartis, Basel, Switzerland;
10. Université Paris-Descartes, Paris, France; 11. Institute of Gerontology, Kings’ College, London, UK. Corresponding author: L. Hugonot-Diener, AP-HP, groupe hospitalier Paris-
centre. Broca Hospital, Department of Geriatrics, 54-56 rue Pascal, 75013 Paris, Francemedforma@pda.fr;
Abstract: Introduction: In Europe the population is ageing rapidly. Older people are taking many medicinal
products daily and these may not necessarily be suitable for them. Publications show that older patients are
underrepresented in clinical trials, especially those over 75 years, with multiple co-morbidities, concomitant
treatments and/or frailty. This document provides a summary of recommendations on ethical aspects of clinical
trials with older people, who may in some cases be considered a vulnerable patient population. The EFGCP’s
Geriatric Medicine Working Party (GMWP) has developed this guidance to promote such research and to support
health care professionals in their efforts. Ethical, scope and context: The definition of a geriatric patient is
reviewed. Frail and vulnerable patients, who are a minority of geriatric patients, should be included whenever it
is relevant. The legal context is described. The process of informed consent: All adults should be presumed
capable of consent, unless proven otherwise; informed consent must be sought for all older people who are able
to consent. A simple, short and easy-to-understand information sheet and consent form will contribute to
improving the readability and understanding of the older participant. A participant guide and the use of a simple
tool to ensure decision making capacity, are recommended. Whenever older people are unable to consent, their
assent should be sought systematically using adequate information, in addition to seeking the consent of their
legal or authorised representative as appropriate. Ethics Committees: Research ethics committees need internal
and/or external geriatric expertise to balance the benefits and risks of research in older people and to appreciate
and recognise their autonomy. Design and Analyses: Design and Analyses should be adapted to the objectives
with appropriate outcomes and are not different from other clinical trials. Conclusions: The absence of proper
recruitment or insufficient presence of older patients in clinical development plans for new medicinal products is
detrimental; there is a need to improve evidence-based knowledge, understanding and management of their
conditions and treatment. The aim of this guidance is to facilitate clinical research for and with the older patient
population. The long version of the guidance will be available on the EFGCP’s website: www.efgcp.be/.
Key words: Clinical trials and research, older people, ethics, guidance, consent, inclusion, frailty, gerontology.
The Journal of Nutrition, Health & Aging©
Volume 17, Number 7, 2013
Received February 25, 2013
Accepted for publication March 19, 2013
10 HUGENOT-DIENER_04 LORD_c 31/07/13 14:20 Page625
Ethical, Scope and Legal Context
The definition of a “geriatric patient” for use in clinical trials
(UEMS-geriatric section, 2008 (1)).
Five main aspects are dominant in this definition:
• Age: “The geriatric population“ is arbitrarily defined, for the
purpose of this guideline, as comprising patients aged 65
years or older. It is important, however, to seek patients in
the older age range, 75 and above, to the best extent
possible. Protocols should not ordinarily include arbitrary
upper age cut offs.
• Gender: to be representative of the geriatric general
population, the proposal recommends that a majority of
women should be recruited, unless there are gender specific
• Functionality/ Frailty: The proposal supports the elaboration
of a consensual definition of frailty, which could be used in
the clinical research setting to be studied. However,
additional research is needed before an operational definition
of frailty can be established (2, 3).
• The number of medicines prescribed: As polypharmacy may
be the consequence of multiple co-morbidities and have
significant interactions itself, the registration of the number
of different medications taken is a good indicator. A
relatively recent overview of the literature indicates that the
two most useful indicators of polypharmacy were the use of
inappropriate medicines or the use of 6 and more
medications at the same time (1).
• Possible exclusion criteria: in order to reflect the
applicability of a particular study to use in this population
the proposal is that when an exclusion criterion is proposed
it must be fully justified.
The vulnerable patient
This concerns a small part of geriatric patients including frail
people: Vulnerability is a condition, which represents ‘Those
who are relatively (or absolutely) incapable of protecting their
own interests’ (CIOMS. 2002 (4)) but may also reflect some
more subtle issues particular to the study population.
The legal framework under which clinical trials are
conducted in older patients includes regulations and guidelines
for Good Clinical Practice. Research in and with the older
person should comply with all relevant legal, regulatory and
ethical guidelines; this includes the ICH E7 and related Q&A
The Process of Informed Consent
The protection of older and vulnerable patients against the
risks inherent in human research is paramount. However, this
should not lead to exclusion of their participation and
subsequent potential benefits. In many instances, older people
wish to and are fully capable of participating in research.
All adults should be presumed capable of consent, unless
proven otherwise: informed consent must be sought in all older
people who are able to consent. A simple, short and easy-to-
understand information sheet and consent form will contribute
to improving the readability and understanding of the older
participant, especially if it is adapted to those with a visual or
other sensory impairment and is supplemented with supportive
tools such as visual and hearing aids, cartoons as applicable,
and a participant guide.
It is advisable to produce a specific participant guide with
simple instructions and information on tests and procedures to
be carried out, the need to be fasting or not, medication taken
on the consultation day, return of bottles etc., contacts, end of
the study or premature stopping arrangements, known &/or new
safety information, publication of results etc.
Use of a simple tool or questions to check if the participant
has understood the given information and implications of
participation is recommended.
Assent from Older and Vulnerable Participants
Where there may be doubt that the older patient has fully
understood the nature, purpose and implications of involvement
in a clinical trial, it will be useful to check this matter with a
simple tool (e.g. UBACC (6, 7) or Newcastle +85) (8).
Then if there is a failure to understand, their assent will not
be sufficient to allow participation in that research, unless it is
supplemented by the assent or consent of a proxy or the legal
representative, as appropriate in that jurisdiction.
Whenever older people are unable to consent, their assent
should still be sought systematically using appropriate
information, in addition to the consent of their legal or
The consent/assent process and assessment of capacity to
consent should always be performed in a supportive and caring
environment with respect for patients’ dignity and rights.
Research ethics committees need internal and/or external
geriatric expertise to balance the benefits and risks of research
in older people and to appreciate and recognise their autonomy.
All members of the research ethics committee including
geriatric experts consulted on an ad hoc basis should be
independent of the sponsor, the investigator and the proposed
research. The qualifications and expertise of the experts used
and the members of the research ethics committee should be
documented and annexed to its opinion. This geriatric expertise
should be available when reviewing the initial protocol and the
subsequent amendments, as well as the follow-up of the study,
until submission of the final report.
Design and Analyses
Design and analyses should be adapted to the research
objectives with appropriate outcomes to this patient population.
A comprehensive geriatric assessment could be used as criteria
MEDICAL RESEARCH FOR AND WITH OLDER PEOPLE IN EUROPE
The Journal of Nutrition, Health & Aging©
Volume 17, Number 7, 2013
10 HUGENOT-DIENER_04 LORD_c 31/07/13 14:20 Page626
for randomisation and for outcomes in designing clinical trials Download full-text
with specific endpoints, such as effects on cognitive function,
balance and falls, urinary incontinence, &/or weight loss, as
appropriate. Patients entering clinical trials, should be
reasonably representative of the population that will be later
treated by the drug.
Geriatric trials should be analysed for potential risks,
including those that may not usually be of concern in younger
people as medicines or procedures may cause adverse effects in
older participants that have not been identified in young adults.
In Europe the population is ageing rapidly. Older people are
daily taking many medicinal products, which may not
necessarily be suitable for them. Publications show that older
patients, especially those over 75 years, with co-morbidities,
concomitant treatments and/or frailty are underrepresented in
clinical trials. Direct extrapolation to older patients of
efficacy/safety data and of the drug benefit/risk profile
observed in younger adults is questionable and does not reflect
daily life and medical practice; all of which may lead to safety
issues and iatrogenic disorders. The absence of proper
recruitment or insufficient presence of older patients in clinical
development plans of new medicinal products is detrimental:
there is a need for improving evidence-based knowledge,
understanding and management of their conditions and
treatment. The aim of this guidance is to facilitate clinical
research in the older population. The long version of the
guidance will be available on the EFGCP’s website:
1. UEMS-geriatric section (2008). The definition of a “geriatric patient” for use in
clinical trials: www.uemsgeriatricmedicine.org/)
Report of CIOMS Working Group VI. WHO ed. (2005). Management of Safety
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doi:10.1093/gerona/gls 119. Epub 2012 Apr 16.
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JNHA: CLINICAL TRIALS AND AGING
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