Selection of outcome measurement instruments for a core outcome set for clinical trials aimed at improving adherence to appropriate polypharmacy in older people

Selection of outcome measurement instruments for a core outcome set for clinical trials targeting interventions aiming to improve adherence to appropriate polypharmacy in older people

Outcomes included in the Core Outcome Set (COS)

The Core Outcome Set (COS) for use in trials aimed at improving adherence to appropriate polypharmacy in older people comprised six outcomes: ‘medication adherence across multiple medications’, ‘treatment burden’, ‘all adverse events and side effects’, ‘health-related quality of life’, ‘healthcare utilisation’, and ‘cost-effectiveness’.¹

A list of 13 Patient-Reported Outcome Measures (PROMs), five objective adherence measures and three measurement methods were compiled from a previous study and different systematic reviews.^2-5 Information cards were prepared and presented to experts in the Delphi consensus exercise (Table 1).

Table 1: The final list of outcomes included in the COS, along with the experts’ information cards for each outcome measurement instruments compiled from systematic reviews,^1,3-4 and another relevant study²

Outcomes	Outcome measurement instruments
Medication adherence across multiple medications	1. The Brief Medication Questionnaire (BMQ)
	2. The Medication Adherence Report Scale (MARS)
	3. The Medical Outcome Study (MOS) – Specific Adherence Scale
	4. The Morisky Medication Adherence Scale-4 (MMAS-4)
	5. Electronic Monitoring Devices (EMDs)
	6. Pill counts
	7. The Medication Possession Ratio (MPR)
	8. The Proportion of Days Covered (PDC)
	9. Daily Polypharmacy Possession Ratio (DPPR)
Suggested instruments	10. The Adherence to Refills and Medications Scale (ARMS)^a
	11. The Medication Adherence Universal Questionnaire (MAUQ)
	12. The Medication Adherence Reasons Scale (MAR-Scale)
Treatment burden	1. Treatment Burden Questionnaire (TBQ)
	2. Multimorbidity Treatment Burden Questionnaire^a
	3. Patient Experience with Treatment and Self-management Questionnaire (PETS)
	4. The Living with Medicines Questionnaire-3^a
Health-related quality of life	1. The 3-level EQ-5D questionnaire (EQ-5D-3L)
	2. The 5-level EQ-5D questionnaire (EQ-5D-5L)^a
	3. The Short Form-12 (SF-12)
	4. The Short Form-36 (SF-36)
	5. The Medication-Related Burden Quality of Life (MRB-QoL) questionnaire^a
All adverse events and side effects	The number of undesired consequences of the intervention (i.e. adverse events or side effects) that result from administering multiple medications in older patients^a
Healthcare utilisation	The number or percentage of a specified utilised service during/in a specified time period that results from administering multiple medications in ol der pa tients^a
Cost-effectiveness	Consulting a health economist about the mos t ap propriate method^a

^aFigures representing the measurement instruments that met the inclusion threshold following the conclusion of the Delphi exercise

Please click on each outcome measurement instrument to see the information card (link to PDF)

This list was voted on in a two-round Delphi questionnaire by academics, healthcare professionals, methodologists, and journal editors (i.e. experts). After the second round, five PROMs and four measurement methods were considered appropriate to be used in studies aimed at improving adherence to appropriate polypharmacy in older patients: the Adherence to Refills and Medications Scale (ARMS), the Living with Medicines Questionnaire-3 (LMQ-3), Multimorbidity Treatment Burden Questionnaire (MTBQ), the 5-level EQ-5D questionnaire (EQ-5D-5L), the Medication-Related Burden Quality of Life (MRB-QoL) questionnaire, ‘the number of undesired consequences of the intervention (i.e. adverse events or side effects) that result from administering multiple medications in older patients’, ‘the number or percentage of a specified utilised service during/in a specified time period that results from administering multiple medications in older patients’, ‘consulting a health economist about the most appropriate method’ and the Daily Polypharmacy Possession Ratio (DPPR).

Public participants’ information cards were prepared following the end of the second round of the Delphi questionnaire (Table 2).

Table 2: The final list of outcomes included in the COS, along with the public participants’ information cards for each outcome measurement instrument
following the end of the second Delphi questionnaire

Outcomes	Outcome measurement instruments
Medication adherence across multiple medications	1. The Adherence to Refills and Medications Scale (AR MS)^a
Medication adherence across multiple medications	2. The Daily Polypha rmacy Possession Ratio (D PPR)
Treatment burden	1. Multimorbidity Treatment Burden Questio nnai re (MTBQ)^a
Treatment burden	2. Th e Living with Medicines Questionnaire-3 (LMQ-3)
Health-related quality of life	1. The 5-level EQ-5D questionnaire (EQ-5D-5L)
Health-related quality of life	2. The Medication-Related Burden Quality of Life (MRB -QoL) questionnaire^a
All adverse events and side effects	The number of undesired consequences of the intervention (i.e. adverse events or side effects) that result from administering multiple medications in old er p atients^a
Healthcare utilisation	The number or percentage of a specified utilised service during/in a specified time period that results from administering multiple medications in older patients
Cost-effectiveness	Consulting a health economist about the most appropriate method

^aFigures showing the measurement instruments that met the threshold for inclusion after the experts’ consensus meeting and the interview with the public
member had concluded.

Please click on each outcome measurement instrument to see the information card (link to PDF)

The resultant list was presented and discussed in a consensus meeting with experts and another separate interview-like meeting with one public member to select one measurement instrument for each outcome.

In the consensus meeting, only the MRB-QoL, ARMS, MTBQ, and ‘the number of undesired consequences of the intervention (i.e. adverse events or side effects) that result from administering multiple medications in older patients’ achieved consensus for inclusion in the final list of measurement instruments.

References

1.          Al Shaker H, Barry H, Hughes C. (2025) Development of a core outcome set for clinical trials targeting interventions aiming to improve adherence to appropriate polypharmacy in older people—an international consensus study. Age and Ageing; 54(4): afaf102.
2.          Cross AJ, Elliott RA, Petrie K, Kuruvilla L, George J. (2020) Interventions for improving medication-taking ability and adherence in older adults prescribed multiple medications. Cochrane Database of Systematic Reviews; 5(5): CD012419.
3.          Patton DE, Pearce CJ, Cartwright M, Smith F, Cadogan CA, Ryan C, Clark E, Francis JJ, Hughes CM. (2021) A non-randomised pilot study of the Solutions for Medication Adherence Problems (S-MAP) intervention in community pharmacies to support older adults adhere to multiple medications. Pilot and Feasibility Studies; 7(1): 18.
4.          Mendoza-Quispe D, Perez-Leon S, Alarcon-Ruiz CA, Gaspar A, Cuba-Fuentes MS, Zunt JR, Montori VM, Bazo-Alvarez JC, Miranda JJ. (2023) Scoping review of measures of treatment burden in patients with multimorbidity: advancements and current gaps. Journal of Clinical Epidemiology; 159: 92-105.
5.          Møller A, Bissenbakker KH, Arreskov AB, Brodersen J. (2020) Specific measures of quality of life in patients with multimorbidity in primary healthcare: a systematic review on patient-reported outcome measures’ adequacy of measurement. Patient Related Outcome Measures; 11: 1-10.