Methods to Assess Patient Preferences in Old Age Pharmacotherapy – A Systematic Review

Figures & data

Table 1 Assessment Evaluating the Adaptability of the Identified Preference Measurement Instruments to the Context of Aged Patients with Polypharmacy (“Polypharmacy Assessment”)

Time budget needed for health care workers to assess patient preferences	▼	High: Health care worker present during the complete process of preference elicitation/Interview mode
	▬	Intermediate: Partly self-administered, partly completed with the help of a health care worker
	▲	Low: Self-administered mode (introduction by a health care worker possible)
Level of cognitive demand imposed on respondents	▼	High: High number of cognitive steps/high amount of time needed to reach an appropriate decision
	▬	Intermediate: Intermediate number of cognitive steps/intermediate amount of time needed to reach an appropriate decision
	▲	Low: Few cognitive steps/short time needed to reach an appropriate decision
Variety of pharmacological aspects represented by the method	▼	Low: Method elicits preferences for < 5 different pharmacological aspects (health outcomes, treatment options or procedural characteristics)
	▬	Intermediate: Method elicits preferences for 5–10 different pharmacological aspects (health outcomes, treatment options or procedural characteristics)
	▲	High: Method elicits preferences for > 10 different pharmacological aspects (health outcomes, treatment options or procedural characteristics)
Link of recorded preferences with specific (pharmacological) treatment strategies	▼	Indistinct: Elicits preferences for very general outcomes or treatment characteristics; no obvious link to a specific treatment
	▬	Moderate: Elicits preferences (eg for the treatment of specific bodily symptoms or for a related group of medications) that hint towards a larger selection of pharmacotherapeutic strategies or elicits preferences for treatment scenarios (lacking a detailed description of all relevant characteristics)
	▲	Distinct: Attributes of the preference elicitation task directly linked with specific pharmacological treatment options during the design of the tool or elicits preferences for detailed and specific treatment scenarios

Figure 1 PRISMA flow diagram of the study screening and selection process.

Table 2 Characteristics of Included Studies

Study	Study Design	Context	Population				Method [#Instrument Number]	Quality Criteria (Validity, Reliability, Understanding)
			Population - Sample Size	Age	Cognition	Affect
Akishita et al 2013^Citation62 (Japan)	Cross-sectional	Priorities of health care outcomes	Community-dwelling, functionally independent older adults n = 2637	All aged ≥ 65 years	NC	NC	Rank prioritization [#47]	Reliability: subgroup tested with second version showed similar results
Baxter et al 2016^Citation79 (United Kingdom)	Cross-sectional	Neovascular age-related macular degeneration	Patients with neovascular age-related macular degeneration n = 87 (100 included, 95 completed task, 8 were excluded for not understanding the task)	Mean = 81 years Range = 67 to 94 years	NC	NC	Conjoint analysis [#7]	Validity: 2 additional scenarios to assess validity; Task testing understanding
Böttger et al 2015^Citation80 (Germany)	Cross-sectional	Anticoagulation therapy in atrial fibrillation	Patients with non-valvular atrial fibrillation n = 486 (647 included, 161 did not complete the interview)	Mean (SD) = 73.9 (8.2) years Median = 75.0 years (All included patients: Mean (SD) = 74.2 (8.7) years Median = 75.0 years)	Comorbidity cognitive impairment: 2.9% (all included patients: 3.9%); Comorbidity dementia: 1.0% (all included patients: 1.7%)	Comorbidity depression: 7.6% (all included patients: 8.5%)	Discrete choice experiment [#13]	Validity: 2 additional scenarios to assess validity (results not reported)
Bowling et al 2008^Citation34 (United Kingdom)	Cross-sectional	Angina	Primary care patients with angina* n = 383 (n for the subgroup aged ≥ 75 years not specified) *Only one of the three studies described in the article met the eligibility criteria	Subgroup aged ≥ 75 years	NC	NC	Likert scale-based questionnaire (“The Patients’ Preferences Questionnaire”) [#23]	Psychometric properties assessed; the final questionnaire was found to be psychometrically sound
Brown et al 2008^Citation35 (USA)	Cross-sectional	Diabetes mellitus type 2	Patients with diabetes mellitus type 2 n = 332 (n = 118 “vulnerable”, n = 214 “nonvulnerable”, Vulnerable Elders Scale VES-13)	All aged ≥ 65 years Subgroup “vulnerable”: mean (SD) = 77 (7) years, subgroup “nonvulnerable”: mean (SD) = 73 (5) years	Diagnosis of dementia and scoring less than 17 points on the MMSE were exclusion criteria	Comorbidity depression: 33% of vulnerable, 13% of nonvulnerable participants; assessed with SF-12 (no data reported)	Time trade-off [#51]	No information reported
Carpenter et al 2007^Citation36 (USA)	Longitudinal	Care preferences and life evaluations in older adults with or without dementia	Older adults without or with very mild or mild dementia n = 64 (no dementia n = 31; very mild dementia n = 16; mild dementia n = 17)	Mean (SD) = 74.6 (5.5) years Range = 62 to 87 years	Comparison of patients with and without very mild or mild dementia (Clinical Dementia Rating 0.5–1.0)	Assessment of positive and negative affect (Dementia Quality of Life instrument)	Likert scale-based questionnaire (“Brief Treatment Planning Questionnaire” with additional questions regarding preferences in dementia care) [#24]	Test-retest reliability after one week, stability after one year; individuals with mild dementia had lower reliability than individuals with no dementia or very mild dementia
Case et al 2013a^Citation58 (USA)	Cross-sectional	Present versus future health - Quantity versus quality of life (Subcontext multimorbidity)	Community-dwelling older adults n = 357	All aged ≥ 65 years Mean (SD) = 76 (7) years	Diagnosis of dementia was exclusion criterion	Depression: 28% in past month	a) Likert scale-based questionnaire (“Time and Outcome [TOP] Scale” → “Attitude Scale”) [#25] To assess construct validity: b) Visual analogue scale (“Now vs Later”) [#54] c) (Health) Outcome Prioritization Tool [#40]	Construct validity: use of 2 other tools assessing the same trade-offs, analysis of patient characteristics associated with favoring quality over quantity of life, correlation of the 2 subscales; Test-retest-reliability; Internal consistency: Cronbach’s α for the 2 subscales
Case et al 2013b^Citation59 (USA)	Cross-sectional	Present versus future health - Quantity versus quality of life (Subcontext multimorbidity)/ Universal health outcomes (Multimorbidity)	Community-dwelling older adults n = 357 (1 did not complete the interview, excluded from analysis)	All aged ≥ 65 years Mean (SD) = 76 (7) years	Diagnosis of dementia was exclusion criterion	Depression (two-item PRIME-MD): 28% in past month	Subcontext multimorbidity: a) Likert scale-based questionnaire (“Attitude Scale”) [#25] b) Visual analogue scale (“Now vs Later”) [#54] Multimorbidity: c) (Health) Outcome Prioritization Tool [#40]	Acceptability and ease of use assessed quantitatively and qualitatively
Case et al 2014^Citation60 (USA)	Cross-sectional	Primary prevention of myocardial infarction	Community-dwelling older adults n = 353 (357 included, 3 responded “Do not understand the question”, 1 had missing data, excluded from analysis)	All aged ≥ 65 years ≥ 75 years: 56%	Diagnosis of dementia was exclusion criterion	NC	a) Likert scale-based questionnaire (“Time and Outcome [TOP] Scale”) [#25] b) Visual analogue scale (“Present vs Future Health Prioritization Tool”) [#54] c) (Health) Outcome Prioritization Tool [#40] d) “Medication willingness” [#31]	Validity: use of 4 tools assessing the same construct; Understanding of the task
Caughey et al 2017^Citation63 (Australia)	Cross-sectional	Prevention of cardiovascular disease and influence of competing health outcomes (Subcontext multimorbidity)	Ambulatory patients with ≥ 2 chronic conditions n = 15	All aged ≥ 65 years Median (IQR) = 79 (73–86) years	Diagnosis of dementia was exclusion criterion	NC	“Medication willingness” [#32]	Reference to Fried et al 2011a^Citation61
Cherniack et al 2008^Citation37 (USA)	Cross-sectional	Use of conventional or complementary and alternative medicine in three medical conditions (Colds, insomnia, back pain)	Ambulatory patients of geriatric clinics n = 338	All aged ≥ 65 years Mean = 77.5 years	NC	NC	Questionnaire (only questions 13–15 applicable) [#44]	No information reported
Chin et al 2008^Citation38 (USA)	Cross-sectional	Diabetes mellitus	Older patients with diabetes n = 473	All aged ≥ 65 years Mean (SD) = 73.7 (5.9) years	NC	SF-12 mental component score: Mean (SD) = 49.9 (6.8)	Time trade-off [#52]	No information reported
Cline & Mott 2003^Citation39 (USA)	Cross-sectional	Preferences for using prescription drugs versus self-treatment strategies (Osteoporosis)	Community-dwelling older women n = 629	All aged ≥ 65 years Mean (SD) = 75.35 (6.23) years	NC	NC	Likert scale-based questionnaire (“Medical Care Preference Scale”) [#26]	Reference to previous study examining the validity and reliability of the “Medical Care Preference Scale”; Internal consistency reliability reported
Cranney et al 2001^Citation40 (Canada)	Longitudinal	Osteoporosis	Women with a recent spine or hip fracture n = 10 (subgroup “vertebral fracture”) n = 10 (subgroup “hip fracture”)	Vertebral fracture: Mean = 75.5 years Range = 65 to 88 years Hip fracture: Mean = 79.5 years Range = 63 to 91 years	NC	Being severely depressed was exclusion criterion; Mean SF-36 Mental health summary score at baseline 43 (vertebral fracture) and 58 (hip fracture)	Feeling Thermometer [#20]	Convergent construct validity: correlation with the HUI2 and the physical health summary of the SF-36; preferences for current health lower in vertebral and hip fracture patients than in wrist or non-fracture patients; Test-retest reliability after 2 weeks; Sensitivity to change
Danner et al 2016^Citation81 (Germany)	Cross-sectional	Age-related macular degeneration	Patients with neovascular age-related macular degeneration n = 86	Median = 75 years	NC	NC	Analytical hierarchy process [#3]	Participants encouraged to “think aloud” during the administration of the instrument to facilitate the interpretation of the quantitative results; Consistency: overall model inconsistency just below 0.2; inconsistency very prevalent at the level of subcriteria
de Vries et al 2015^Citation88 (Netherlands)	Cross-sectional	Antihypertensive medication in diabetes mellitus type 2	Patients with diabetes mellitus type 2 n = 45 (participants in the subgroup aged ≥ 75 years included in the analysis)	Subgroup aged ≥ 75 years: Mean (SD) = 79 (3.6) years	NC	NC	Discrete choice experiment [#14]	Dominant choice set to test understanding of the task: 10 participants (mean age (SD) = 70 (10) years) in the total study sample (n = 161) failed and were excluded from the analysis
Decalf et al 2017^Citation64 (Belgium)	Cross-sectional	Overactive bladder	Community-dwelling and hospitalized older people with and without complaints of overactive bladder n = 276 (informed consent given by 304 people, 28 excluded from analysis)	All aged ≥ 65 years Median (IQR) = 75 (69–80) years ≥ 80 years: n = 71 (26%)	11 participants excluded from the analysis because of suspected cognitive problems	EQ-5D: n = 52 (19%) reported problems on the dimension “Anxiety/Depression”; this group was found to be unable to make consistent choices in the discrete choice experiment	Discrete choice experiment [#15]	Rationality test with additional choice set to test the participants’ understanding of the questionnaire: 3 participants excluded from the analysis because they did not pass the test
Extermann et al 2003^Citation41 (cross-national, France and USA)	Cross-sectional	Cancer (Willingness to undergo chemotherapy)	Cancer outpatients and geriatric outpatients without history of cancer n = 195	All aged ≥ 70 years Mean = 77 years Range = 70 to 95 years	Diagnosis of dementia was exclusion criterion	GDS (Short Form) mean (SD) 2.2–4.9 (2.6–3.7); GDS score not associated with willingness to accept chemotherapy in multivariate analysis	“Medication willingness” [#33]	No information reported
Fraenkel et al 2015^Citation89 (USA)	Cross-sectional	Preference for the status quo in chronic disease (Rheumatoid arthritis)	Patients with rheumatoid arthritis n = 42 (subgroup aged ≥ 65 years)	Subgroup aged ≥ 65 years	NC	NC	Adaptive conjoint analysis [#1]	Content validity/comprehensibility: literature review + expert opinion
Fried et al 2011a^Citation61 (USA)	Cross-sectional	Primary prevention of myocardial infarction	Community-dwelling older adults n = 356 (1 participant failed to complete the interview, excluded from the analyses)	Mean (SD) = 76 (7) years	Diagnosis of dementia was exclusion criterion	Depression assessed as “health characteristic”; not associated with willingness to take the preventive medication	“Medication willingness” [#32]	Understanding: 4 participants responded “do not understand” to ≥ 1 scenarios; 4 additional participants gave discrepant responses
Fried et al 2011b^Citation65 (USA)	Cross-sectional	Universal health outcomes (Multimorbidity)	Older adults with hypertension and fall risk n = 81	All aged ≥ 65 years ≥ 85 years: 30%	Diagnosis of dementia was exclusion criterion (Parent study Tinetti et al 2008b^Citation52)	Depressive symptoms (score ≥ 2 on PHQ-2): 43% of participants	(Health) Outcome Prioritization Tool [#40]	Face validity: cognitive interviews with n = 10 participants; Construct validity: association of patient characteristics associated with a preference for life-sustaining treatment with ranking “keeping you alive” as most important; Test-retest reliability after one week evaluated as “fair to poor”; Understanding: rated by interviewers (13% of participants: no/very poor understanding of the task)
Fuller et al 2004^Citation42 (United Kingdom)	Cross-sectional	Stroke prevention (Anticoagulation with warfarin)	Patients attending a general elderly medicine outpatient clinic n = 81	All aged ≥ 65 years Median = 81 years Range = 66 to 97 years	Cognitive impairment was exclusion criterion	NC	“Medication willingness” [#34]	Accompanying qualitative analysis of decision making
Fyffe et al 2008^Citation43 (USA)	Cross-sectional	Depression	Home-care patients n = 28	Mean (SD) = 77 (9.7) years Range = 62 to 95 years	21% scored < 24 on MMSE	25% met criteria for a current depressive disorder (on SCID-I)	Rank prioritization [#48]	Accompanying qualitative analysis of decision making
Girones et al 2012^Citation66 (Spain)	Prospective	Lung cancer	Patients with lung cancer n = 83	All aged ≥ 70 years Mean (SD) = 77 (5.1) years Range = 70 to 91 years ≥ 80 years: 28.9%	26.4% scored < 21 on MMSE	31.3% > 3 on GDS	Direct choice [#9]	Content validity: scenarios based on data from the literature
Gum et al 2010a^Citation82 (USA)	Cross-sectional	Distress (Stress and sadness)	Adults participating in community health screenings n = 140	All aged ≥ 60 years Mean (SD) = 76.48 (7.56) years	NC	Frequency of distress assessed	Choose and rank [#4]	Content validity and comprehensibility pilot tested
Gum et al 2010b^Citation83 (USA)	Cross-sectional	Stress and sadness	Adults receiving home-based aging services n = 142	All aged ≥ 60 years Mean (SD) = 74.7 (8.3) years	Diagnosis of dementia was exclusion criterion; assessed with 3MS (detailed results reported)	Assessed with SCID and BSI-18 (n = 17: any depressive disorder on SCID); assessment of self-identified behavioral health problem	Choose and rank [#4]	See Gum et al 2010a
Hamelinck et al 2016^Citation90 (Netherlands)	Cross-sectional	Early breast cancer	Women with early primary breast cancer n = 29 (subgroup aged ≥ 65 years)	Subgroup aged ≥ 65 years	Presence of cognitive/mental problems was exclusion criterion	Depression considered as part of assessment for “geriatric health condition”	Probability trade-off technique [#42]	Accompanying qualitative analysis of decision making
Holbrook et al 2007^Citation44 (Canada)	Cross-sectional randomized trial	Anticoagulation treatment in atrial fibrillation	Patients (family practices, geriatric day clinical program) without atrial fibrillation or warfarin treatment n = 98	All aged ≥ 65 years Mean (SD) = 73.6 (6.1)	Eligible patients were “cognitively intact”	NC	Decision aid [#8]	Validity and reliability pilot tested
Jimenez et al 2012^Citation67 (USA)	Cross-sectional	Mental health	Patients with depression, anxiety or at-risk alcohol abuse n = 2208	All aged ≥ 65 years Mean (SD) in subgroups = 70.5–74.1 (5.0–6.2) years	Parent study: severe cognitive impairment was exclusion criterion (≥ 16 on short Orientation-Memory-Concentration Test)	Eligible participants screened positive for depression, anxiety or at-risk alcohol abuse	Questionnaire (“Cultural Attitudes toward Healthcare and Mental Illness Questionnaire”) [#45]	No information reported
Junius-Walker et al 2011^Citation68 (Germany)	Cross-sectional	Multimorbidity	Community-dwelling primary care patients n = 123	All aged ≥ 70 years Mean (SD) = 77.7 (5.4) years	“Limited consent capabilities” was exclusion criterion; Health domain “cognitive malfunction” (Clock-drawing test) problem for 45.5% of participants	Health domain “problems with mood” (depression, mourning) problem for 49.6% of participants	Complex intervention (Geriatric (STEP) assessment + rating of relevant health problems on Likert scale) [#6]	Content validity: geriatric (STEP) assessment covering multiple health domains; development process and feasibility study of STEP assessment referenced
Junius-Walker et al 2012^Citation69 (Germany)	Cluster randomized controlled trial	Multimorbidity	Independently living primary care patients n = 317	All aged ≥ 70 years Mean = 77.2 years	“Limited mental capability” was exclusion criterion; Health domain “cognitive malfunction” (Clock-drawing test) part of STEP assessment (results reported)	Health domain “mood” part of STEP assessment	Complex intervention (Geriatric (STEP) assessment + rating of relevant health problems on Likert scale + priority setting consultation; PrefCheck Intervention) [#6]	Reference to Junius-Walker et al 2011^Citation68
Junius-Walker et al 2015^Citation70 (Germany)	Cross-sectional	Multimorbidity	Primary care patients n = 826	All aged ≥ 72 years Mean (SD) = 79 (4.4) years	“Inability to consent” was exclusion criterion; Health domain “Cognition” (Clock-drawing test) positive in 31.4% of participants	Health domain “mood” (STEP assessment): problem in 37.5% (mourning), 10.9% (depression), 5.0% (loneliness) and 4.7% (anxiety) of participants	Complex intervention (Geriatric (STEP) assessment + rating of relevant health problems on Likert scale) [#6]	Reference to Junius-Walker et al 2011^Citation68
König et al 2014^Citation84 (Switzerland)	Cross-sectional	Alzheimer’s disease	Patients with mild to moderate Alzheimer’s disease n = 126	Mean = 75 years Range = 52 to 91 years	Clinical Dementia Rating score > 6 in ≈ 31% of patients	(Depression considered in parent study, different sample size)	Willingness to pay [#55]	Construct validity: confirmation of predefined hypothesis of altruism
Landreville et al 2001^Citation45 (Canada)	Cross-sectional	Depression	Patients of family medicine clinics n = 200	All aged ≥ 65 years Mean (SD) = 73.13 (5.98) years	NC	Mean (SD) GDS score 6.29 (5.24)	Likert scale (Case descriptions + 3 Treatment descriptions + Modified version of the “Treatment Evaluation Inventory”) [#28]	Reference to previous study (validation of case descriptions; validity, test-retest-reliability and internal consistency of modified “Treatment Evaluation Inventory”)
Luck-Sikorski et al 2017^Citation71 (Germany)	Cross-sectional	Depression	Primary care patients with and without depression n = 1230	All aged ≥ 75 years Mean (SD) = 80.6 (4.66) years	Presence of moderate or severe dementia was exclusion criterion; Mean (SD) MMSE score 27.3 (2.46)	GDS: 14.0% with mild (score 4–5), 15.9% with moderate (score ≥ 6) depressive symptoms; preferred treatment options analyzed in regard to GDS score	Likert scale + Ranking [#29]	No information reported
Mandelblatt et al 2010^Citation72 (USA)	Prospective cohort study	Breast cancer (Chemotherapy)	Women with invasive nonmetastatic breast cancer n = 801	All aged ≥ 65 years Mean (SD) = 73 (6.1) years Range = 65 to 100 years	Blessed test: 0 errors = 49% (no cognitive impairment); ≥ 1 error = 51%; ≥ 11 errors = exclusion criterion	NC	(Modified) Time trade-off [#53]	Relationship between preferences for chemotherapy and actual receipt of chemotherapy analyzed
Man-Son-Hing et al 2000^Citation46 (Canada)	Cross-sectional	Primary prevention of stroke and myocardial infarction with aspirin	Primary care patients without manifest atherosclerotic disease and without indication or contraindication for regular aspirin use n = 42	All aged ≥ 65 years Mean = 71 years Range = 65 to 85 years	(Cognitive status was assessed, data not reported)	NC	a) Individualized decision analysis [#21] b) Probability trade-off technique [#43]	Evaluation of the results of both methods by the participants; descriptions of health states previously pilot tested for content and comprehensibility (reference)
Miller et al 1998^Citation31 (USA)	Cross-sectional	Frailty	Older adults (community health clinic, public housing for seniors, geriatric medicine clinics, retirement community) n = 359	All aged ≥ 60 years Mean (SD) = 76.8 (7.4) years	Diagnosis of dementia and “too confused to participate” were exclusion criteria	NC	Likert scale-based questionnaire [#27]	No information reported
Mohlman 2012^Citation73 (USA)	Cross-sectional	Anxiety	Older adults n = 383 (433 surveys received, 50 excluded (incomplete or suspected misunderstanding of instructions))	All aged ≥ 65 years Mean (SD) = 75.21 (7.38) Range = 65 to 97 years Three subgroups: young-old (65–74 years), middle-old (75–84 years), oldest-old (≥ 85 years)	(Pilot tested with non-demented adults; cognition not considered in actual study)	BAI: mean (SD) = 8.46 (5.02); BDI: mean (SD) = 5.98 (6.73); STAI-trait: mean (SD) = 38.99 (11.31)	Direct choice (in response to a scenario) [#10]	Pilot tested
Mueller et al 2016^Citation85 (Germany)	Cross-sectional (after observational period)	Neovascular age-related macular degeneration	Patients with neovascular age-related macular degeneration n = 284 (337 included, 53 excluded from analysis due to incomplete or inconsistent responses)	All aged ≥ 50 years Mean (SD) = 77.4 (7.1) years	NC	NC	Discrete choice experiment [#16]	Additional scenarios and exclusion of participants giving inconsistent responses (no detailed results reported)
Murphy et al 2002^Citation47 (USA)	Cross-sectional	Prevention of myocardial infarction, stroke, hip fracture	Patients of a hospital-based geriatrics clinic n = 409	Mean = 81 years	Patients with dementia and/or inability to fully understand the questions were excluded	Mental illness was exclusion criterion	“Medication willingness” [#35]	Pilot tested; Reproducibility: interview repeated with 30 patients after two months
Muth et al 2016^Citation53 (Germany)	Cluster randomized controlled pilot study	Multimorbidity	Primary care patients with ≥ 3 chronic conditions and ≥ 5 chronic prescriptions n = 100 (94 completed the study)	All aged ≥ 65 years Intervention group: mean (SD) = 75.8 (6.70) Control group: mean (SD) = 75.2 (5.88) Median = 75 years Range = 64 to 93 years	Cognitive impairment (MMSE < 26) was exclusion criterion	GDS score: intervention group: mean (SD) = 2.2 (2.12), control group: mean (SD) = 1.7 (1.89)	Questionnaire (“MediMol” questionnaire; only questions 16–18 applicable) [#46]	No information reported
Nyman et al 2005^Citation48 (Sweden)	Prospective	Locally advanced prostate cancer	Patients with locally advanced prostate cancer n = 150 (149 completed the questionnaires at entry, 148 at follow-up)	Mean = 75 years Range = 57 to 89 years	(“No mental handicap” was inclusion criterion)	NC	Direct choice (after standardized written information) + questionnaire [#12]	Assessment of the patients’ satisfaction with the chosen treatment three months after the direct choice
Perret-Guillaume et al 2011^Citation74 (Switzerland)	Cross-sectional	Antihypertensive therapy	Patients hospitalized at a geriatric hospital n = 120	All aged > 70 years Mean (SD) = 83.8 (7.4) years	Presence of cognitive disorders (MMSE < 18) was exclusion criterion; MMSE score ≥ 26 in 55% of participants	GDS 4 items: score = 0/4 in 67% of participants	“Medication willingness” [#36]	Consistency of responses between scenarios reported
Pfisterer et al 2007^Citation49 (Germany)	Cross-sectional	Urinary incontinence	Geriatric inpatients n = 117	All aged ≥ 80 years Mean (SD) = 84.6 (3.9) years	MMSE ≤ 27 was exclusion criterion	NC	Paired comparisons (on 11-point visual analogue scale; information leaflets) [#41]	Pilot tested; Consistency of individual ratings assessed
Protheroe et al 2000^Citation50 (United Kingdom)	Cross-sectional	Atrial fibrillation	Patients with atrial fibrillation n = 97	All aged 70 to 85 years Mean (SD) = 77 (3.9) years	NC	NC	Individualized decision analysis (including ranking of health outcomes and time trade-off exercises) [#22]	No information reported
Raue et al 2011^Citation75 (USA)	Cross-sectional	Depression	Home care patients n = 256	All aged ≥ 65 years Mean (SD) = 78.2 (7.1) years Range = 65 to 96 years	Dementia and/or MMSE ≤ 20 were exclusion criteria	SCID-I; 7% major depression, 9% minor depression; Hamilton Depression Rating Scale; Clinical Anxiety Scale	Choose and rank (“Cornell Treatment Preference Index”) [#5]	Reference to previous study examining the association of treatment preferences (assessed with the “Cornell Treatment Preference Index”) with various outcomes (eg adherence) in depressed patients
Rochon et al 2014^Citation76 (USA)	Cross-sectional	Osteoarthritis of the knee	Patients with osteoarthritis of the knee n = 58	All aged ≥ 65 years	NC	NC	Adaptive conjoint analysis [#2]	Accompanying qualitative analysis (focus groups with n = 29 participants) of user experience
Schnabel et al 2014^Citation54 (Germany)	Cross-sectional	Complementary and alternative medicine	Older adults (community-dwelling, self-reliant or assisted by home care; residents of retirement or nursing homes) n = 400	All aged ≥ 70 years Mean (SD) = 81.8 (7.4) years	(No detailed data reported, but study population included participants with legal guardian)	NC	Direct choice [#11]	No information reported
Schonberg et al 2014^Citation55 (USA)	Longitudinal	Breast cancer	Women receiving breast biopsy n = 164	All aged ≥ 65 years Age groups 65–74 and ≥ 75 years	Dementia was exclusion criterion; assessed with Short Blessed Test (detailed results reported)	NC	“Medication willingness” [#37]	No information reported
Silverman et al 2013^Citation77 (USA)	Cross-sectional	Osteoporosis	Postmenopausal women at risk for osteoporotic fractures n = 367	All aged ≥ 65 years Means (SD) in 4 subgroups 74.7 (7.1) to 79.7 (7.1) years	NC	Health status assessment including depressive symptoms	a) Rank prioritization [#49] b) Maximum difference scaling [#30]	Pilot tested
Sudlow et al 1998^Citation32 (United Kingdom)	Cross-sectional	Atrial fibrillation (Anticoagulants)	Patients with atrial fibrillation n = 179	All aged ≥ 65 years	MMSE, 26% scoring < 24	NC	“Medication willingness” [#38]	No information reported
Tinetti et al 2008a^Citation51 (USA)	Cross-sectional	Competing cardiovascular disease, medication symptoms and fall injury outcomes (Subcontext multimorbidity)	Senior housing residents with hypertension and fall risk n = 13	All aged ≥ 70 years Mean (SD) = 83 (9.3) years Range = 71 to 96 years	Cognitive impairment was exclusion criterion (score < 15 on the telephone version of the MMSE); mean (SD) 19 (2.0); median 19; range = 15–21 (of 22 items)	NC	Discrete choice experiment [#17]	Pretest (n = 15); Test-retest reliability; Tested for order effects; Obvious choice task to test understanding (all 13 participants passed)
Tinetti et al 2008b^Citation52 (USA)	Cross-sectional	Competing cardiovascular disease, medication symptoms and fall injury outcomes (Subcontext multimorbidity)	Persons with hypertension and fall risk n = 123 (2 additional individuals failed to complete the choice task and were excluded)	All aged ≥ 70 years Mean (SD) = 81.5 (5.9) years Range = 70 to 96 years	Diagnosis of dementia or MMSE (telephone version) < 15 were exclusion criteria; 21.1% with MMSE < 19; exclusion of individuals who failed a simple choice task (18.4% of otherwise eligible persons)	32.0% with depressive symptoms (score ≥ 2 on PHQ-2)	Discrete choice experiment [#17]	Reference to Tinetti et al 2008a^Citation51
Uemura et al 2016^Citation86 (Japan)	Cross-sectional	Castration-resistant prostate cancer	Patients with castration-resistant prostate cancer n = 133 (134 included, 1 person excluded from main analyses for giving inconsistent responses)	Mean (SD) = 75.36 (7.39) years	(Participants had to be able to complete the survey by themselves)	NC	Discrete choice experiment [#18]	Additional choice set with dominant scenario to test understanding
van Summeren et al 2016^Citation57 (Netherlands)	Cross-sectional (Pilot study)	Universal health outcomes (Multimorbidity)	Primary care patients with polypharmacy (≥ 5 chronic medications) and multimorbidity (≥ 2 chronic conditions) n = 60	All aged ≥ 69 years Mean (SD) = 83.8 (4.2) years	Cognitive impairment (failing to understand the four health outcomes) was exclusion criterion	NC	(Health) Outcome Prioritization Tool [#40]	Acceptability and practicability (including the patients’ understanding of the task) evaluated with semi-structured questionnaires and in-depth interviews
van Summeren et al 2017^Citation56 (Netherlands)	Cross-sectional (Follow-up study)	Universal health outcomes (Multimorbidity)	Primary care patients with polypharmacy (≥ 5 chronic medications) and multimorbidity (≥ 2 chronic conditions) n = 59	All aged ≥ 69 years Median (IQR) = 83 (81–86) years	Cognitive impairment was exclusion criterion	NC	(Health) Outcome Prioritization Tool [#40]	Reference to van Summeren et al 2016,^Citation57 Fried et al 2011b^Citation65 and one additional previous study by Fried et al
Vennedey et al 2016^Citation87 (Germany)	Cross-sectional	Neovascular age-related macular degeneration	Patients with neovascular age-related macular degeneration n = 86	Median = 75 years	NC	NC	Discrete choice experiment [#19]	Pilot tested; Duplicate choice set to test consistency; Participants rated the difficulty of the choice task; Participants encouraged to “think aloud” during the administration of the instrument to facilitate the interpretation of the quantitative results
Voigt et al 2010^Citation78 (Germany)	Cross-sectional	Multimorbidity	Primary care patients n = 35	All aged ≥ 70 years Mean = 77.7 years	Severe dementia was exclusion criterion; Health domain “cognition” part of STEP assessment (detailed results reported)	Health domain “Mood” part of STEP assessment	Complex intervention (Geriatric (STEP) assessment + rating of relevant health problems on Likert scale) [#6]	Content validity: geriatric (STEP) assessment covering multiple health domains; development process of STEP assessment referenced
Yellen et al 1994^Citation33 (USA)	Cross-sectional	Cancer	Cancer patients n = 42 (subgroup aged ≥ 65 years)	Subgroup aged ≥ 65 years: Mean = 70.7 years ≥ 75 years: n = 10	NC	NC	a) “Medication willingness” (“Treatment-Acceptance Vignettes”) [#39] b) “Switch-Point Vignettes” [#50]	No information reported

Abbreviations: 3MS, Modified Mini-Mental State Examination; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; Blessed test, Blessed Orientation-Memory-Concentration test; BSI-18, Brief Symptom Inventory-18; EQ-5D, EuroQol 5-Dimensions questionnaire; GDS, Geriatric Depression Scale; HUI2, Health Utilities Index Mark 2; IQR, interquartile range; MMSE, Mini-Mental State Examination; NC, not considered; PHQ-2, Patient Health Questionnaire-2; PRIME-MD, Primary Care Evaluation of Mental Disorders; SCID, Structured Clinical Interview for DSM-III-R; SCID-I, Structured Clinical Interview for DSM-IV Axis I Disorders; SD, standard deviation; SF-12, Medical Outcomes Study 12-Item Short Form Health Survey; SF-36, Medical Outcomes Study 36-Item Short Form Health Survey; STAI-trait, State Trait Anxiety Inventory (trait scale); STEP, Standardized Assessment for Elderly Patients in Primary Care.

Table 3 Results of the “Polypharmacy Assessment” (Assessment Evaluating the Adaptability of the Identified 55 Preference Measurement Instruments to the Context of Aged Patients with Polypharmacy)

	Method	Instrument Number/Study	Time Budget	Cognitive Demand	Variety of Aspects	Link with Treatment	Comments	Trade-Offs
1.	Adaptive conjoint analysis	#1 Fraenkel et al 2015^Citation89	▼	▼	▬	▲		Yes
		#2 Rochon et al 2014^Citation76	▲	▼	▬	▲		Yes
2.	Analytical hierarchy process	#3 Danner et al 2016^Citation81	▼	▬	▬	▲		Yes
3.	Choose and rank	#4 Gum et al 2010a,^Citation82 2010b^Citation83	▼	▲	▼	▬		Yes
		#5 Raue et al 2011^Citation75	▼	▲	▼	▬		Yes
4.	Complex intervention	#6 Junius-Walker et al 2011,^Citation68 2012,^Citation69 2015,^Citation70 Voigt et al 2010^Citation78	▼	▲	▲	▬		No
5.	Conjoint analysis	#7 Baxter et al 2016^Citation79	▼	▼	▬	▲		Yes
6.	Decision aid	#8 Holbrook et al 2007^Citation44	▼	▬	▼	▲		Yes
7.	Direct choice (between different options)	#9 Girones et al 2012^Citation66	▼	Insufficient data	▼	▲		No
		#10 Mohlman 2012^Citation73	▬	▲	▼	▬		No
		#11 Schnabel et al 2014^Citation54	▲/▼	▲	▼	▬		No
8.	Direct choice + Questionnaire	#12 Nyman et al 2005^Citation48	▲	Insufficient data	▼	▲		Yes
9.	Discrete choice experiment	#13 Böttger et al 2015^Citation80	▼	▬	▬	▲		Yes
		#14 de Vries et al 2015^Citation88	▲	▼*	▬	▲	*Cognitive demand: 6 attributes, changing probability data within attribute levels, 3 options per choice set	Yes
		#15 Decalf et al 2017^Citation64	▲/▼	▬	▼	▬*	*Link with treatment: link to treatment strategies only at the level of side effects	Yes
		#16 Mueller et al 2016^Citation85	▼	▬	▼	▲		Yes
		#17 Tinetti et al 2008a,^Citation51 2008b^Citation52	▼	▬	▼	▲		Yes
		#18 Uemura et al 2016^Citation86	▲	▼*	▬	▲	*Cognitive demand: 6 attributes, changing probability data within attribute levels	Yes
		#19 Vennedey et al 2016^Citation87	▼	▬	▬	▲		Yes
10.	Feeling thermometer	#20 Cranney et al 2001^Citation40	▼	▬	▬	▬		Yes
11.	Individualized decision analysis	#21 Man-Son-Hing et al 2000^Citation46	▼	▬*	▼	▲	*Cognitive demand: assessment of health states on visual analogue scale	No
		#22 Protheroe et al 2000^Citation50	▼	▼*	▼	▲	*Cognitive demand: ranking of 9 health states + time trade-off	Yes
12.	Likert scale	#23 Bowling et al 2008^Citation34	Insufficient data	▲	▼	▬		No
		#24 Carpenter et al 2007^Citation36	▼	▲	Insufficient data*	Insufficient data*	*Missing information regarding exact questionnaire items	No
		#25 Case et al 2013a,^Citation58 2013b,^Citation59 2014^Citation60	▼	▬	▼	▬	“Attitude Scale”/“Time and Outcome Preference (TOP) Scale”	Yes
		#26 Cline & Mott 2003^Citation39	▲	▲	▼	▼		No
		#27 Miller et al 1998^Citation31	▲/▼	▲	▼	▬		No
		#28 Landreville et al 2001^Citation45	▲/▼	▬	▼	▬		No
13.	Likert scale + Ranking	#29 Luck-Sikorski et al 2017^Citation71	▼	▲	▼	▬		Yes
14.	Maximum difference scaling	#30 Silverman et al 2013^Citation77	▲/▼	▬	▬	▲		Yes
15.	“Medication willingness“	#31 Case et al 2014^Citation60	▼	▬	▼	▲	Single question regarding preventive medication	No
		#32 Version 1: Fried et al 2011a^Citation61 Version 2: Caughey et al 2017^Citation63	▼	▼	▬/▼*	▲	*Version 2 (Caughey et al 2017) covers also competing health outcomes	Yes
		#33 Extermann et al 2003^Citation41	▲	▬	▼	▲		Yes
		#34 Fuller et al 2004^Citation42	▼	▬	▬	▲		Yes
		#35 Murphy et al 2002^Citation47	▼	▬	▼	▬		Yes
		#36 Perret-Guillaume et al 2011^Citation74	▼	▼	▼	▲		Yes
		#37 Schonberg et al 2014^Citation55	▼	▲	▼	▬		No
		#38 Sudlow et al 1998^Citation32	▼	▲	▼	▬		No
		#39 Yellen et al 1994^Citation33	▼	▼	▼	▲	“Treatment-Acceptance Vignettes”	Yes
16.	Outcome Prioritization Tool	#40 Case et al 2013b,^Citation59 2014,^Citation60 Fried et al 2011b,^Citation65 van Summeren et al 2016,^Citation57 2017^Citation56	▼	▬	▼	▬/▼*	*Link with treatment: items vary in practical implications	Yes
17.	Paired comparisons	#41 Pfisterer et al 2007^Citation49	▼	▬	▼	▬		Yes
18.	Probability trade-off technique	#42 Hamelinck et al 2016^Citation90	▼	▼	▼	▲		Yes
		#43 Man-Son-Hing et al 2000^Citation46	▼	▼	▼	▲		Yes
19.	Questionnaire	#44 Cherniack et al 2008^Citation37	▬	▲	▼	▬	Only part of the questionnaire assesses preferences, items 13 to 15 considered	No
		#45 Jimenez et al 2012^Citation67	▼	▲	▼	▬		No
		#46 Muth et al 2016^Citation53	▼	▲	▬	▬	Only part of the “MediMol” questionnaire assesses preferences, items 16 to 18 considered	No
20.	Rank prioritization	#47 Akishita et al 2013^Citation62	▲	▬	▲	▼		Yes
		#48 Fyffe et al 2008^Citation43	▼	▲	▼	▬		Yes
		#49 Silverman et al 2013^Citation77	▲/▼	▲	▼	▬		Yes
21.	Switch-Point Vignettes	#50 Yellen et al 1994^Citation33	▼	▼	▼	▲		Yes
22.	Time trade-off	#51 Brown et al 2008^Citation35	▼	▼	▲	▲		Yes
		#52 Chin et al 2008^Citation38	▼	▼	▬	▲		Yes
		#53 Mandelblatt et al 2010^Citation72	▼	▼	▼	▬		Yes
23.	Visual analogue scale	#54 Case et al 2013b,^Citation59 2014^Citation60	▼	▲	▼	▼	“Now vs Later”/”Present vs Future Health Prioritization”	Yes
24.	Willingness to pay	#55 König et al 2014^Citation84	▼	▬	▼	▲		Yes

Notes: Time budget = Time budget needed for health care workers to assess patient preferences; Cognitive demand = Level of cognitive demand imposed on respondents; Variety of aspects = Variety of pharmacological aspects represented by the method; Link with treatment = Link of recorded preferences with specific (pharmacological) treatment strategies; Trade-offs = Instrument requires the respondent to make trade-offs between competing medical problems (Yes or No).

▼→ Negative rating: High (time budget, cognitive demand), Low (variety of aspects), Indistinct (link with treatment); ▬ → Intermediate/Moderate rating: Intermediate (time budget, cognitive demand, variety of aspects), Moderate (link with treatment); ▲ → Positive rating: Low (time budget, cognitive demand), High (variety of aspects), Distinct (link with treatment); ▲/▼ Low or High (time budget); ▬/▼Intermediate or Low (variety of aspects), Moderate or Indistinct (link with treatment).

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