Impact of Medication Regimen Simplification on Medication Adherence and Clinical Outcomes in Patients with Long-Term Medical Conditions

Figures & data

Figure 1 The process of identification, screening, and inclusion of papers for this review.

Table 1 Studies That Reported Simplification of Drug Regimens (N=17)

Author and Country	Study Design	Study Population	Objectives/Rationale
Angela et al 2010^Citation6 USA	Retrospective cohort study involved	75 patients on ARV regimens.	Examine the impact of pharmacist’s intervention on adherence and clinical outcomes of ARV regimens.
Rubio et al 2010^Citation15 Spain	Prospective cohort study	183 HIV-infected patients on protease inhibitors (PIs) therapy.	Determine the effectiveness and adherence and of simplified once-daily dosing of atazanavir boosted with ritonavir (ATV/r).
Buscher et al 2012^Citation16 USA	Prospective cohort study	99 newly diagnosed HIV patients.	To determine the effect of ART dosing frequency and number of pills on the adherence of newly diagnosed HIV patients.
Pallela et al 2014^Citation17 USA	Randomized open-label trial	476 HIV-1 RNA suppressed patients	To examine the efficacy of antiretroviral simplification from a ritonavir-boosted protease inhibitor therapy (NRTI) to STR.
Fabbiani et al 2014^Citation18 Italy	Retrospective cohort study	553 patients on EFV containing regimens.	Determine the risk of therapy interruption of STR compared to BID or OD EFV therapy.
Arroyo et al 2016^Citation19 Spain	Retrospective study	264 patients on ART treatment	Evaluate the influence of the number of daily pills and daily doses on treatment adherence in a 7-year pharmaceutical care program.
Velvanathan et al 2016^Citation20 Malaysia	Randomized control trial.	120 of HIV patients	Compare the clinical outcomes, adherence of patients on FDC vs FRC containing emtricitabine (FTC), tenofovir (TDF), and efavirenz (EFV).
Chen et al 2017^Citation21 USA	Randomized control trial	Involved 750 HIV patients.	To assess adherence barriers in correlation with STR, single-dose MTR, and multi-dose MTR of ART.
Laliberte’ et al 2013^Citation14 USA	Retrospective cohort study	5756 patients with venous thromboembolism (VTE).	Evaluate the adherence rates between OD and BID chronic medication regimens for DM and HTN in patients with VTE.
Stange et al 2013^Citation7 Germany	Prospective, semi-randomized trial	240 adult inpatients with HTN, DM, and/or dyslipidemia.	To examine the impact of structured pharmacist’s intervention on healthcare providers on reducing the complexity of the medication regimen.
Pauly et al 2015^Citation10 Germany	Prospective open clinical trial	269 psychiatric patients.	Assess the effect of multi-dimensional interventions in improving adherence to complex regimen therapy.
Barnebey & Robin 2017^Citation13 USA	Randomised controlled trial	81 adult patients diagnosed with open-angle glaucoma or ocular hypertension.	To assess the adherence of TTFC with unfixed agents of travoprost and timolol (TRAV+ TIM).
Taybani et al 2019^Citation23 Hungary	Prospective single-arm clinical trial	62 patients with T2DM.	Assess the impact of switching insulin therapy from MDI to the once-daily fixed-ratio combination.
Oh C.K et al 2020^Citation25 South Korea	Prospective cohort trial	160 kidney transplant recipients.	Evaluate the medication adherence of tacrolimus, sirolimus, and corticosteroids as a simplified once-daily immunosuppressive regimen.
Dudl et al 2009^Citation24 USA	Three-year observational study	170,024 patients with diabetes, CAD, or both.	To assess the effect of promoting a bundle of fixed doses of a generic statin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB),
Sluggett et al 2020^Citation26 Australia	Pre-planned secondary analysis of a cluster randomized controlled trial	242 residents of eight residential aged care facilities (simplification was done for 62 residents in interventional arm)	To evaluate the impact of a medication regimen simplification on medication administration times, falls, hospitalization and mortality at 12 months follow up.
S.F Dos Santos et al^Citation22 2020 Brazil	Retrospective cohort study	1206 patients using MTR of efavirenz, tenofovir and lamivudine who switched to the STR.	To evaluate the impact of switching from MTR to STR on adherence to cART.

Table 2 Simplification Strategies of Drug Regimens and Its Impact on Outcome Measures (N=17)

Author and Country	Simplification Strategy	Outcome Measures (Adherence)	Outcome Measures (Clinical)	Impact on Outcomes
Angela et al 2010^Citation6 USA	Reducing pill burden and dosing frequency	Refill records	CD4 count	Increase treatment adherence and improve clinical outcomes.
Rubio et al 2010^Citation15 Spain	Once-daily dosing	Self-reported	Assessment of virological failure	Retained virological response with a slight improvement in adherence.
Buscher et al 2012^Citation16 USA	Once-daily dosing	Visual analogue scale.	Assessment of treatment failure (HIV-RNA levels)	Greater adherence with no difference in clinical outcomes.
Palella et al 2014^Citation17 USA	Single tablet regimen	Visual analogue scale.	Virological suppression	Maintained virological suppression. No difference in adherence.
Fabbiani et al 2014^Citation18 Italy	Single tablet regimen	Treatment discontinuation	Virological suppression	Higher adherence and lower virological failure
Arroyo et al 2016^Citation19 Spain	Reducing daily doses and pills	Dispensing records	No assessment	Higher adherence levels.
Velvanathan et al 2016^Citation20 Malaysia	Fixed-dose combination	Morisky scores	CD4 count	Improved clinical outcomes and patients` adherence.
Chen et al 2017^Citation21 USA	Single tablet regimen	Pill counts	CD4 count Viral load ((HIV-RNA levels)	Higher medication adherence and lower viral load
Laliberte’ et al 2013^Citation14 USA	Once-daily dosing	MPR and PDC > 80%	No assessment	Higher adherence
Stange et al 2013^Citation7 Germany	Reducing the number and frequency of medications	Self-reported MARS-D	No assessment	No significant change in adherence.
Pauly et al 2015^Citation10 Germany	Decrease dosing frequency Discontinue unnecessary drugs	MARS	No assessment	Enhanced adherence
Barnebey and Robin 2017^Citation13 USA	Fixed-dose combination	Dosing aid records	IOP reduction	Better adherence. IOP reductions were similar.
Taybani et al 2019^Citation23 Hungary	Once-daily dosing Fixed-dose combination	Indirect (decrease treatment burden)	HbA1c level Glycaemic control	Effective decreased treatment burden and may improve adherence to therapy.
Oh C.K et al 2020^Citation25 South Korea	Once-daily dosing	Self-reported (TBS scores)	Biopsy confirmed acute rejection (BCAR)	Improved adherence without risk of treatment failure.
Dudl et al 2009^Citation24 USA	Fixed-dose combination	Indirect (medication bundle exposure)	Risk of hospitalization for MI or stroke in the following year.	Higher medication exposure and decreased risk of MI or stroke hospitalization.
Sluggett et al 2020^Citation26 Australia	Long-acting and combination formulations	Indirect (reduce times of medication administration)	Risk of falls, hospitalization, and mortality.	Significant reduction of medication administration times. Higher risk of falls. No significant differences were observed for risk of hospitalization or mortality.
Dos Santos et al 2020^Citation22 Brazil	Single tablet regimen	Proportion of days covered (PDC≥95%)	Viral load	Significant increase in adherence levels with no difference in viral load outcomes

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Rubio R, Serrano O, Carmena J, et al. Effect of simplification from protease inhibitors to boosted atazanavir-based regimens in real-life conditions. HIV Med. 2010;11(9):545–553. doi:10.1111/j.1468-1293.2010.00827.x

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Palella FJ, Fisher M, Tebas P, et al. Simplification to rilpivirine/emtricitabine/tenofovir disoproxil fumarate from ritonavir-boosted protease inhibitor antiretroviral therapy in a randomized trial of HIV-1 RNA-suppressed participants. AIDS. 2014;28(3):335–344. doi:10.1097/QAD.0000000000000087

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Fabbiani M, Zaccarelli M, Grima P, et al. Single tablet regimens are associated with reduced efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients. BMC Infect Dis. 2014;14(1):1–8. doi:10.1186/1471-2334-14-26

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Velvanathan T, Islahudin F, Sim BLH, Taha NA. Simplification of HAART therapy on ambulatory HIV patients in Malaysia: a randomized controlled trial. Pharm Pract (Granada). 2016;14(4):1–8. doi:10.18549/PharmPract.2016.04.830

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Laliberte F, Bookhart BK, Nelson WW, et al. Impact of once-daily versus twice-daily dosing frequency on adherence to chronic medications among patients with venous thromboembolism. Patient. 2013;6(3):213–224. doi:10.1007/s40271-013-0020-5

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Stange D, Kriston L, Von-Wolff A, Baehr M, Dartsch DC. Reducing cardiovascular medication complexity in a German University Hospital: effects of a structured pharmaceutical management intervention on adherence. J Manag Care Pharm. 2013;19(5):396–407.

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Pauly A, Wolf C, Mayr A, Lenz B, Kornhuber J, Friedland K. Effect of a multi-dimensional and inter-sectoral intervention on the adherence of psychiatric patients. PLoS One. 2015;10(10):1–18. doi:10.1371/journal.pone.0139302

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Barnebey HS, Robin AL. Adherence to fixed-combination versus unfixed travoprost 0.004%/timolol 0.5% for glaucoma or ocular hypertension: a randomized trial. Am J Ophthalmol. 2017;176:61–69. doi:10.1016/j.ajo.2016.12.002

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Taybani Z, Bótyik B, Katkó M, Gyimesi A, Várkonyi T. Simplifying complex insulin regimens while preserving good glycemic control in type 2 diabetes. Diabetes Ther. 2019;10(5):1869–1878. doi:10.1007/s13300-019-0673-8

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Oh CK, Bang JB, Kim SJ, et al. Improvement of medication adherence with simplified once-daily immunosuppressive regimen in stable kidney transplant recipients: a prospective cohort study. Asian J Surg. 2020;43(6):660–667. doi:10.1016/j.asjsur.2019.07.011

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Dudl RJ, Wang MC, Wong M, Bellows J. Preventing myocardial infarction and stroke with a simplified bundle of cardioprotective medications. Am J Manag Care. 2009;15(10):88–94.

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Sluggett JK, Hopkins RE, Chen EY, et al. Impact of medication regimen simplification on medication administration times and health outcomes in residential aged care: 12 month follow up of the SIMPLER randomized controlled trial. J Clin Med. 2020;9(4):1053. doi:10.3390/jcm9041053

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