International core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy

Background: Comparisons of clinical trial findings in systematic reviews can be hindered by the heterogeneity of the outcomes reported. Moreover, the outcomes that matter most to patients might be underreported. A core outcome set can address these issues, as it defines a minimum set of outcomes that should be reported in all clinical trials in a particular area of research. The objective in this study was to develop a core outcome set for clinical trials of medication review in multi-morbid older patients with polypharmacy.

Methods: Firstly, eligible outcomes were identified through a systematic review of trials of medication review in older patients (=65 years) and interviews with 15 older patients. Secondly, an international three-round Delphi survey in four countries involving patients, healthcare professionals, and experts was conducted to validate outcomes to be included in the core outcome set. Consensus meetings were conducted to validate the results.

Results: Of the 164 participants invited to take part in the Delphi survey, 150 completed Round 1, including 55 patients or family caregivers, 55 healthcare professionals, and 40 experts. A total of 129 participants completed all three rounds. Sixty-four eligible outcomes were extracted from 47 articles, 32 clinical trial protocols, and patient interviews. Thirty outcomes were removed and one added after Round 1, 18 outcomes were removed after Round 2, and seven after Round 3. Results were discussed during consensus meetings. Consensus was reached on seven outcomes, which constitute the core outcome set: drug-related hospital admissions; drug overuse; drug underuse; potentially inappropriate medications; clinically significant drug-drug interactions; health-related quality of life; pain relief.

Conclusions: We developed a core outcome set of seven outcomes which should be used in future trials of
medication review in multi-morbid older patients with polypharmacy.


Anne Spinewine (PI)1, Jean-Baptiste Beuscart1, Olivia Dalleur1, Benoit Boland1, Stefanie Thevelin1
Denis O’Mahony2
Wilma Knol3, Paul Jansen3
Anette Van Dorland4, Nicolas Rodondi4
Lisa Pont5, Johana Westbrook5

1) Clinical Pharmacy research group, Louvain Drug Institute, Université Catholique de Louvain, Belgium
2) Department of Medicine (Geriatrics), University College Cork, Ireland
3) Department of Geriatric Medicine, University Medical Centre Utrecht, Netherlands
4) Department of General Internal Medicine, Universität Bern, Switzerland
5) Centre for Health Systems and Safety Research, Australian Institute of Health Innovation, Macquarie University, Sidney, Australia


Journal: BMC Mediine
Volume: 16
Issue: 21
Pages: -
Year: 2018
DOI: 10.1186/s12916-018-1007-9

Further Study Information

Current Stage: Not Applicable
Date: July 2015 - May 2016
Funding source(s): This work is part of the project “OPERAM: OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly” supported by the European Commission (EC) HORIZON 2020, proposal 634238, and by the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract number 15.0137.

Health Area

Disease Category: Health care of older people

Disease Name: Polypharmacy

Target Population

Age Range: 65 - 100

Sex: Either

Nature of Intervention: Drug

Stakeholders Involved

- Clinical experts
- Consumers (caregivers)
- Consumers (patients)
- Patient/ support group representatives
- Policy makers
- Researchers

Study Type

- COS for clinical trials or clinical research


- Consensus meeting
- Delphi process
- Interview
- Systematic review

Systematic review:
Update of an existing recent systematic review on medication review in the elderly
Systematic search on the Cochrane Library and on RCTs registries (EU, USA, WHO registries)
Selection and data extraction by two independent researchers

Patients and caregivers. Eligible patients are patients aged 65 and older taking at least 5 medications.
semi-structured approach for one-to-one interviews by using open-ended questions
Audio recordings fully transcribed, stored, and analysed using NVivo10® software
The analysis conducted according to an interpretative approach

Delphi process:
Participants: patients, carers, healthcare professionals (GPs, other physicians, pharmacists, nurses), researchers, experts
Four European centres in Belgium, Ireland, Netherlands, and Switzerland
3 Rounds with online or paper-based survey. Older patients will get assistance for completing the survey if needed.

Consensus meetings were conducted to validate the results.