A framework for understanding sources of bias in medication adherence research
Open accessAbstract
The sources of bias in medication adherence research have not been comprehensively explored. We aimed to identify biases expected to affect adherence research and to develop a framework for mapping these onto the phases of adherence (initiation, implementation and discontinuation). A literature search was conducted, key papers were reviewed and a Catalogue of Bias was consulted. The specific biases related to adherence measurement and metrics were mapped onto the phases of adherence using a tabular matrix. Twenty‐three biases were identified, of which 11 were specifically relevant to adherence measures and metrics. The mapping framework showed differences in the numbers and types of biases associated with each measure and metric while highlighting those common to many adherence study designs (e.g., unacceptability bias and apprehension bias). The framework will inform the design of adherence studies and the development of risk of bias tools for adherence research.
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.
Integrity signals
Registry
Cites
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.
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?
Refill records may attribute treatment gaps to patients even when discontinuation was clinician-directed.
“Additionally, refill records may attribute treatment gaps to patients, even when discontinuation was clinician-directed.130,131,134”
From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [134]
The Results (Table 3; page unavailable) identify information bias and insensitive-measure bias for medication-possession metrics during discontinuation. The paper therefore supports the general concern that refill-based measures can misclassify adherence, but the passages found do not specifically say they attribute clinician-directed discontinuation to patients. (LLM, conf=0.78)
Experimental — accuracy not yet measuredPersistence measures derived from databases such as claims data cannot confirm actual medication use and may misclassify patients who switch insurers as nonadherent.
“Persistence measures derived from databases, such as claims data, cannot confirm actual medication use and may misclassify patients who switch insurers as nonadherent.130,131,134”
From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [134]
Framework development (section 2.2; page unavailable) distinguishes analysis of prescription or claims databases and medication-possession scores from observed medication-taking and biomarker measures. This supports the point that database-derived measures cannot confirm actual use. The paper does not address patients switching insurers or their resulting classification as nonadherent (searched: insurer and insurance switching). (LLM, conf=0.78)
Experimental — accuracy not yet measuredSelf-reported adherence is simple and cost-effective but prone to recall and social desirability bias.
“Self-reported adherence is simple and cost-effective but prone to recall and social desirability bias.130,131,133,134”
From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [134]
Table 3 in the Results maps both recall or memory bias and social desirability bias to questionnaire or interview adherence scores. The Discussion also identifies self-reports as subjective measures associated with bias. The passages from our copy do not establish that self-reported adherence is simple or cost-effective. (LLM, conf=0.84)
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
The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., et al. (2021) · BMJ · doi:10.1136/bmj.n71 · Cited by 108,283 · see citing works
A new taxonomy for describing and defining adherence to medications
Vrijens, B., De Geest, S., Hughes, D. A., Przemyslaw, K., Demonceau, J., Ruppar, T., Dobbels, F., Fargher, E., Morrison, V., Lewek, P., et al. (2012) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04167.x · Cited by 2,028 · see citing works
Self-citationMedication adherence outcomes of 771 intervention trials: Systematic review and meta-analysis
Conn, V. S., & Ruppar, T. M. (2017) · Preventive Medicine · doi:10.1016/j.ypmed.2017.03.008 · Cited by 367 · see citing works
Accurate Assessment of Adherence
Daniels, T., Goodacre, L., Sutton, C., Pollard, K., Conway, S., & Peckham, D. (2011) · Chest · doi:10.1378/chest.09-3074 · Cited by 210 · see citing works
Shrivastava, T. P., Goswami, S., Gupta, R., & Goyal, R. K. (2023) · Journal of Diabetes Science and Technology · doi:10.1177/19322968211060060 · Cited by 46 · see citing works
Flagged first, then by citations
Research works printed but not linked: 46
- Wright DFB, Sinnappah KA, Hughes DA. Medication Adherence Research Comes of Age. Br J Clin Pharmacol. 2023;89(7):1914-1917. doi:10.1111/bcp.15722 · DOI
- Haynes RB, Taylor DW, Sackett DL (Eds). Compliance in Health Care. Johns Hopkins University Press; 1979.
- Sackett DL, Haynes RB (Eds). Compliance with Therapeutic Regimens. Johns Hopkins University Press; 1974.
- De Geest S, Zullig LL, Dunbar-Jacob J, Hughes D, Wilson IB, Vrijens B. Improving medication adherence research reporting: ESPA- COMP Medication Adherence Reporting Guideline (EMERGE). Ann Intern Med. 2018;169(1):30-35. doi:10.7326/M18-0543 · DOI · Paper page
- Dima AL, Allemann SS, Dunbar-Jacob J, Hughes DA, Vrijens B, Wilson IB. TEOS: a framework for constructing operational definitions of medication adherence based on Timelines-Events-Objectives- Sources. Br J Clin Pharmacol. 2021;87(6):2521-2533. doi:10.1111/ bcp.14659 · DOI
- Dima AL, Allemann SS, Dunbar-Jacob J, Hughes DA, Vrijens B, Wilson IB. Methodological considerations on estimating medication adherence from self-report, electronic monitoring and electronic healthcare databases using the TEOS framework. Br J Clin Pharmacol. 2023;89(7):1918-1927. doi:10.1111/bcp.15375 · DOI
- Kelly A, Crimston-Smith L, Tong A, et al. Scope of outcomes in trials and observational studies of interventions targeting medication adherence in rheumatic conditions: a systematic review. J Rheumatol. 2020;47(10):1565-1574. doi:10.3899/jrheum.190726 · DOI
- Serhal S, Mitchell B, Krass I, et al. Rethinking the gold standard-the feasibility of randomized controlled trials within health services effec- tiveness research. Res Social Adm Pharm. 2022;18(9):3656-3668. doi: 10.1016/j.sapharm.2022.03.017 · DOI
- Sinnappah KA, Stocker SL, Chan JS, Hughes DA, Wright DFB. Clinical interventions to improve adherence to urate-lowering therapy in patients with gout: a systematic review. Int J Pharm Pract. 2022;30(3): 215-225. doi:10.1093/ijpp/riac025 · DOI
- Anghel LA, Farcas AM, Oprean RN. An overview of the common methods used to measure treatment adherence. Med Pharm Rep. 2019;92(2):117-122. doi:10.15386/mpr-1201 · DOI · Paper page
- Grant MJ, Booth A. A typology of reviews: an analysis of 14 review types and associated methodologies. Health Info Libr J. 2009;26(2): 91-108. doi:10.1111/j.1471-1842.2009.00848.x · DOI · Paper page
- Andrikopoulou E, Scott P, Herrera H, Good A. What are the important design features of personal health records to improve medication adherence for patients with long-term conditions? A systematic liter- ature review. BMJ Open. 2019;9(9):e028628. doi:10.1136/bmjopen- 2018-028628 · DOI
- Conn VS, Ruppar TM, Chan KC, Dunbar-Jacob J, Pepper GA, De Geest S. Packaging interventions to increase medication adherence: systematic review and meta-analysis. Curr Med Res Opin. 2015;31(1): 145-160. doi:10.1185/03007995.2014.978939 · DOI
- Conn VS, Ruppar TM, Chase JA, Enriquez M, Cooper PS. Interven- tions to improve medication adherence in hypertensive patients: sys- tematic review and meta-analysis. Curr Hypertens Rep. 2015;17(12): 94. doi:10.1007/s11906-015-0606-5 · DOI
- Fidler A, Sweenie R, Ortega A, Cushing CC, Ramsey R, Fedele D. Meta-analysis of adherence promotion interventions in pediatric asthma. J Pediatr Psychol. 2021;46(10):1195-1212. doi:10.1093/ jpepsy/jsab057 · DOI
- Ho SC, Chong HY, Chaiyakunapruk N, Tangiisuran B, Jacob SA. Clini- cal and economic impact of non-adherence to antidepressants in major depressive disorder: a systematic review. J Affect Disord. 2016; 193:1-10. doi:10.1016/j.jad.2015.12.029 · DOI · Paper page
- Hussain T, Nassetta K, O'Dwyer LC, Wilcox JE, Badawy SM. Adher- ence to immunosuppression in adult heart transplant recipients: a sys- tematic review. Transplant Rev (Orlando). 2021;35(4):100651. doi:10. 1016/j.trre.2021.100651 · DOI
- Manon SM, Phuong JM, Moles RJ, et al. The role of community phar- macists in delivering interventions for osteoporosis: a systematic review. J Am Pharm Assoc. 2003;62(6):1741-9.e10.
- Mathes T, Grospietsch K, Neugebauer EAM, Pieper D. Interventions to increase adherence in patients taking immunosuppressive drugs after kidney transplantation: a systematic review of controlled trials. Syst Rev. 2017;6(1):236. doi:10.1186/s13643-017-0633-1 · DOI
- Mbuagbaw L, Sivaramalingam B, Navarro T, et al. Interventions for enhancing adherence to antiretroviral therapy (ART): a systematic review of high quality studies. AIDS Patient Care STDS. 2015;29(5): 248-266. doi:10.1089/apc.2014.0308 · DOI
- McCullough AR, Ryan C, Macindoe C, et al. Behavior change theory, content and delivery of interventions to enhance adherence in chronic respiratory disease: a systematic review. Respir Med. 2016; 116:78-84. doi:10.1016/j.rmed.2016.05.021 · DOI
- Mellon L, Doyle F, Hickey A, et al. Interventions for increasing immu- nosuppressant medication adherence in solid organ transplant recipi- ents. Cochrane Database Syst Rev. 2022;9:CD012854. doi:10.1002/ 14651858.CD012854.pub2 · DOI
- Ng R, Carter SR, El-Den S. The impact of mobile applications on medi- cation adherence: a systematic review. Transl Behav Med. 2020;10(6): 1419-1435. doi:10.1093/tbm/ibz125 · DOI
- Nieuwlaat R, Wilczynski N, Navarro T, et al. Interventions for enhanc- ing medication adherence. Cochrane Database Syst Rev. 2014;2014 (11):CD000011. doi:10.1002/14651858.CD000011.pub4 · DOI · Paper page
- Normansell R, Kew KM, Stovold E. Interventions to improve adher- ence to inhaled steroids for asthma. Cochrane Database Syst Rev. 2017;4:CD012226. doi:10.1002/14651858.CD012226.pub2 · DOI
- Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collabora- tion's tool for assessing risk of bias in randomised trials. BMJ. 2011; 343(7829):889-893. doi:10.1136/bmj.d5928 · DOI · Paper page
- Asamoah-Boaheng M, Bonsu KO, Farrell J, Oyet A, Midodzi WK. Measuring medication adherence in a population-based asthma administrative pharmacy database: a systematic review and meta- analysis. Clin Epidemiol. 2021;13:981-1010. doi:10.2147/CLEP. S333534 · DOI
- Vollmer WM, Xu M, Feldstein A, Smith D, Waterbury A, Rand C. Comparison of pharmacy-based measures of medication adherence. BMC Health Serv Res. 2012;12(1):155. doi:10.1186/1472-6963- 12-155 · DOI
- Atkinson TM, Rodriguez VM, Gordon M, et al. The association between patient-reported and objective oral anticancer medication adherence measures: a systematic review. Oncol Nurs Forum. 2016; 43(5):576-582. doi:10.1188/16.ONF.576-582 · DOI
- Murali KM, Mullan J, Roodenrys S, Cheikh Hassan HI, Lonergan MA. Exploring the agreement between self-reported medication adher- ence and pharmacy refill-based measures in patients with kidney dis- ease. Patient Prefer Adherence. 2022;16:3465-3477. doi:10.2147/ PPA.S388060 · DOI
- Kalichman SC, Amaral CM, Swetzes C, et al. A simple single-item rat- ing scale to measure medication adherence: further evidence for con- vergent validity. J Int Assoc Physicians AIDS Care. 2009;8(6):367-374. doi:10.1177/1545109709352884 · DOI
- Berg KM, Arnsten JH. Practical and conceptual challenges in measur- ing antiretroviral adherence. J Acquir Immune Defic Syndr. 2006;43- (Suppl 1):S79-S87. doi:10.1097/01.qai.0000248337.97814.66 · DOI
- Buono EW, Vrijens B, Bosworth HB, Liu LZ, Zullig LL, Granger BB. Coming full circle in the measurement of medication adherence: opportunities and implications for health care. Patient Prefer Adher- ence. 2017;11:1009-1017. doi:10.2147/PPA.S127131 · DOI
- Elseviers M, Vrijens B. Assessment of medication adherence in field research. In: Elseviers M, Wettermark B, Almarsd ottir A, et al., eds. Drug Utilization Research: Methods and Applications. Wiley Online Library; 2016:361-368. doi:10.1002/9781118949740.ch35 · DOI
- Hawkshead J, Krousel-Wood MA. Techniques for measuring medica- tion adherence in hypertensive patients in outpatient settings: advan- tages and limitations. Dis Manag Health Out. 2007;15(2):109-118. doi: 10.2165/00115677-200715020-00006 · DOI
- Lehmann A, Aslani P, Ahmed R, et al. Assessing medication adher- ence: options to consider. Int J Clin Pharmacol. 2014;36(1):55-69. doi: 10.1007/s11096-013-9865-x · DOI
- Mason M, Cho Y, Rayo J, Gong Y, Harris M, Jiang Y. Technologies for medication adherence monitoring and technology assessment criteria: narrative review. JMIR Mhealth Uhealth. 2022;10(3):e35157. doi:10. 2196/35157 · DOI
- Stirratt MJ, Dunbar-Jacob J, Crane HM, et al. Self-report measures of medication adherence behavior: recommendations on optimal use. Transl Behav Med. 2015;5(4):470-482. doi:10.1007/s13142-015-0315-2 · DOI · Paper page
- Valencia S, Leon M, Losada I, Sequera VG, Fernandez Quevedo M, Garcia-Basteiro AL. How do we measure adherence to anti- tuberculosis treatment? Expert Rev Anti Infect Ther. 2017;15(2):157- 165. doi:10.1080/14787210.2017.1264270 · DOI
- Van Der Straten A, Montgomery ET, Hartmann M, Minnis A. Method- ological lessons from clinical trials and the future of microbicide research. Curr HIV/AIDS Rep. 2013;10(1):89-102. doi:10.1007/ s11904-012-0141-9 · DOI
- Williams AB, Amico KR, Bova C, Womack JA. A proposal for quality standards for measuring medication adherence in research. AIDS Behav. 2013;17(1):284-297. doi:10.1007/s10461-012-0172-7 · DOI
- De Vera MA, Marcotte G, Rai S, Galo JS, Bhole V. Medication adher- ence in gout: a systematic review. Arthritis Care Res (Hoboken). 2014; 66(10):1551-1559. doi:10.1002/acr.22336 · DOI
- Donoghue K, Hermann L, Brobbin E, Drummond C. The rates and measurement of adherence to acamprosate in randomised controlled clinical trials: a systematic review. PLoS ONE. 2022;17(2):e0263350. doi:10.1371/journal.pone.0263350 · DOI
- Zullig Leah L, Mohammad S, Renee A, Colette W, Coleman M, Oeffinger KC. Adherence to cardiovascular disease risk factor medi- cations among patients with cancer: a systematic review. Int J Clin Pharmacol. 2022;44(1):288.
- Bender B, Milgrom H, Apter A. Adherence intervention research: what have we learned and what do we do next? J Allergy Clin Immu- nol. 2003;112(3):489-494. doi:10.1016/S0091-6749(03)01718-4 · DOI
- Murali KM, Lonergan M. Breaking the adherence barriers: strategies to improve treatment adherence in dialysis patients. Semin Dial. 2020; 33(6):475-485. doi:10.1111/sdi.12925 · DOI
Cited by
Sorted by citations
Adherence to PCSK9 Inhibitors in Clinical Practice
Blais, J. E., Zhong, W., Li, C. Y. V., Kongkaew, C., & Chan, A. H. Y. (2026) · JACC: Advances · doi:10.1016/j.jacadv.2026.102733 · Cited by 7 · see citing works
- Authors
- Sinnappah, K. A., Hughes, D. A., Stocker, S. L., Vrijens, B., Aronson, J. K., & Wright, D. F. B.
- Affiliations
- University of Otago (NZ)
- Bangor University (GB)
- The University of Sydney (AU)
- University of Liège (BE)
- University of Oxford (GB)
- Corresponding author
- Wright, Daniel F. B.
- ORCID
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2023-08-08
- Volume
- 89
- Issue
- 11
- Pages
- 3444-3453
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- OpenAlex
- W4385295586
- Cited by
- 17
- References
- 5
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 3
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Bangor University Research Portal (Bangor University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Family Practice › Medication Adherence and Compliance
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Social Sciences › Sociology and Political Science › Survey Methodology and Nonresponse
- Keywords
- medication adherence, bias, risk of bias, adherence measurement, risk of bias tools, research design
- MeSH terms
- Humans, Bias, Medication Adherence
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
