Impact of reducing dosing frequency on adherence to oral therapies: a literature review and meta-analysis

Figures & data

Figure 1 Search terms and strategy for identifying relevant studies.

Table 1 Search terms and initial strategy for identifying relevant studies

Search number	Search strings
1	(once OR twice OR thrice OR one OR two OR three) NEAR/1 (daily* OR per*day) OR ‘OD’:ab,ti OR ‘BID’:ab,ti OR ‘TID’:ab,ti OR ‘QID’:ab,ti
2	adhere*:ab,ti OR nonadhere*:ab,ti OR (non NEAR/1 adhere*):ab,ti OR complian*:ab,ti OR noncomplian*:ab,ti OR (non NEAR/1 complian*):ab,ti OR ‘medication possession’:ab,ti OR mpr:ab,ti OR ‘persistence’:ab,ti OR (non NEAR/1 persist*):ab,ti OR nonpersisten*:ab,ti OR ‘medication possession ratio’ OR ‘treatment refusal’ OR ‘medication compliance’/exp OR medication NEAR/1 complian* OR medication NEAR/1 persisten* OR medication NEAR/1 adhere*
3	patient NEAR/1 (monitoring OR care OR counselling)
4	#2 OR #3
5	#1 AND #4

Table 2 Summary of included studies for a dosage frequency comparison in medication treatments for chronic diseases

Disease sub-type	Study	Intervention	Number of patients	Mean duration (range) of follow-up in weeks	Study country(ies)	Outcome assessed
Hypertension	Cells^Citation43	Isradipine RF: BID	12	9.4	NR	Compliance
		Isradipine MR: OD	12
	Baird^Citation29	Betaioc® Durules®: OD	193	NR	Canada and UK	Compliance
		Betaloc®: BID	196
	Maro^Citation34	Antihypertensive: OD	61	156	Tanzania	Compliance*
		Antihypertensive: BID	34
		Antihypertensive: TID	51
	Turki^Citation40	Antihypertensive: OD	209	NR	Malaysia	Adherence*
		Antihypertensive: BID	148
		Antihypertensive: ≥TID	23
	Girvin^Citation44	Enalapril: OD	25	16	Ireland	Compliance
		Enalapril: BID	25
	Andrejak^Citation30	Trandolapril: OD	71	26	France	Compliance*
		Captopril: BID	62
	Boissel^Citation45	Nicardipine: TID	3636	12	France	Compliance
		Nicardipine SR: BID	3638
Angina pectoris	Brown^Citation46,†	ISMN: OD	NR	NR	UK	Cost (total, direct, and indirect)
		ISMN: BID	NR
	Kardas^Citation47	Betaxolol: OD	56	10	Poland	Compliance*
		Metoprolol tartrate: BID	56
Cardiovascular disorders	Bae^Citation49	Cardiovascular regimen: BID	1,077,936	NR	NR	Adherence*
		Cardiovascular regimen: OD
Atrial fibrillation	Song^Citation10	Carvedolol: OD	28,384	NR	NR	Persistence*
		Carvedolol: BID
		Amlodipine: OD
		Captopril: TID
Acute coronary syndrome (ACS)	Hess^Citation37	Carvedilol at 6 months: OD	168	52	NR	Persistency,
		Carvedilol at 6 months: BID	2086			MPR, compliance
		Metformin at 6 months: OD	136
		Metformin at 6 months: BID	614
		Carvedilol at 12 months: OD	168
		Carvedilol at 12 months: BID	2086
		Metformin at 12 months: OD	136
		Metformin at 12 months: BID	614
Heart transplant	Doesch^Citation48	Tacrolimus/Cyclosporin A: BID	50	4	NR	Adherence*
		Tacrolimus: OD	50
Depression	McLaughlin^Citation36	Bupropion: OD	756	NR	USA	Persistence*
		Bupropion: BID	2382
	Granger^Citation39	Bupropion: OD	142	NR	NR	Adherence*
		Bupropion: BID	349
	Stang^Citation6	Bupropion: TID	31
		Bupropion SR: BID	12,468	NR	USA	Persistence*, adherence,
	Stang^Citation50	Bupropion XL: OD	257,049			MPR
		Bupropion SR: BID	1917	39	USA	Persistence*, MPR
		Bupropion XL: OD	1074
Schizophrenia	Pfeiffer^Citation52	Antipsychotic medication: OD	1381	NR	USA	Adherence*
		Antipsychotic medication:	258
		Multiple daily dosing
Epilepsy	Cramer^Citation51	Antiepileptics: OD regimen	3	14	NR	Compliance*
		Antiepileptics: BID regimen	12
		Antiepileptics: TID regimen	7
		Antiepileptics: QID regimen	4
Pain	Carlos^Citation54,†	Duloxetine: OD	NR	13	Mexico	Cost-effectiveness*
		Gabapentin: TID	NR
		Pregabalin: BID	NR
Migraine	Mulleners^Citation53	Propranolol: OD	11	NR	UK	Compliance
		Atenolol: BID	11
		Pizotifen or methysergide: TID	7
Type 2 Diabetes	Winkler^Citation27	Sulfonylureas OD: adherence by pill count > 90%	11	7.7	Germany	Adherence*
		Sulfonylureas OD: adherence by MEMS (dosage) > 90%	11
		Sulfonylureas OD: adherence by MEMS (regimen) > 90%	11
		Sulfonylureas OD: adherence by pill count 90%–110%	11
		Sulfonylureas OD: adherence by MEMS (dosage) 90%–110%	11
		Sulfonylureas OD: adherence by MEMS (regimen) 90%–110%	11
		Sulfonylureas BID/TID: adherence by pill count > 90%	8
		Sulfonylureas BID/TID: adherence by MEMS (dosage) > 90%	8
		Sulfonylureas BID/TID: adherence by MEMS (regimen) > 90%	8
		Sulfonylureas BID/TID: adherence by pill count 90%–110%	8
		Sulfonylureas BID/TID: adherence by MEMS (dosage) 90%–110%	8
		Sulfonylureas BID/TID: adherence by MEMS (regimen) 90%–110%	8
	Dezii^Citation7	Glipizide GITS: OD	746	51.3	NR	Adherence index*, persistence*
		Glipizide: BID	246
	Kardas^Citation55	Gliclazide MR: OD	55	16	Poland	Compliance*
		Glibenclamide: BID	50
	Pullar^Citation33	Phenobarbital: BID	59	4	England	Compliance*, inadequate compliance, safety
		Phenobarbital: BID	60
		Phenobarbital: TID	60
	Charpentier^Citation56	Glimepiride: OD	100	26 (10-week dose titration and 16-week maintenance period)	France	Compliance*
		Glibenclamide: BID/TID	101
HIV/AIDS	Carrieri^Citation8	HAART: OD	1110	260	France	Non-adherence*
		HAART: BID
		HAART: ≥TID
	Negredo^Citation25	HAART: OD	85	48	NR	Adherence
		HAART: BID	84
	Stone^Citation57	ART: ≤2 doses daily (self-reported)	170	NR	USA	Adherence
		ART: ≥3 doses daily (self reported)	119
		ART: ≤2 doses daily (correct)	141
		ART: ≥3 doses daily (correct)	148
	AbelIan^Citation58	Ritonavir: BID	45	NR	Spain	Adherence*
		Indinavir: TID	70
		Saquinavir: TID	49
	Echarri Martinez^Citation35	HAART: OD	75	26	Spain	Adherence*
		HAART: BID	217
		HAART: TID	6
	Moyle^Citation38	ART: OD	15	NR	France, Germany, Italy, Spain,, UK	Adherence*
		ART: BID	255
		ART: TID	109
		ART: >TID	58
Respiratorytract infections (RTI)	Kardas^Citation31	Respiratory tract infection therapy: OD	250	0.9	Poland	Compliance*
		Respiratory tract infection therapy: BID	251
	Kardas^Citation32	Clarithromycin: OD	60		Poland	Compliance*
		Clarithromycin: BID	62
Community-acquired pneumonia/acute bronchitis	Spiritus^Citation59,†	Clarithromycin: BID	311	2	USA	Health care resource utilization*
		Erythromycin stearate: QID	321
		Cefaclor: TID	302
Streptococcal pharyngitis	Raz^Citation60	Penicillin V: BID	51	4	NR	Compliance
		Penicillin V: QID	53
Renal transplantation	Abecassis^Citation61,†	Tacrolimus + mycophenolate mofetil: OD	NR	NR	USA	Economic outcomes (patient treatment cost)*
		Tacrolimus + mycophenolate mofetil: BID	NR
	Sidhu^Citation9,†	Tacrolimus: OD	NR	NR	UK	Economic outcomes
		Tacrolimus: BID	NR
Liver transplant	Eberlin^Citation62	Tacrolimus OD: post transplantation duration > 6 months to <2 years	16	52	NR	Compliance*
		Tacrolimus OD: post transplantation duration > 2 to <5 years	22
		Tacrolimus OD: post transplantation duration > 5 years	21
		Tacrolimus BID: post transplantation duration > 6 months to <2 years	15
		Tacrolimus BID: post transplantation duration > 2 to <5 years	23
		Tacrolimus BID: post transplantation duration > 5 years	22
Ulcerative colitis	Hawthorne^Citation28	Asacol®: OD	103	52	UK	Adherence
		Asacol®: TID	110
	Lachaine^Citation63	Mesalamine at 13 weeks: OD	12	52	Canada	Adherence*, persistence*, compliance
		Mesalamine at 13 weeks: >OD	10
		Mesalamine at 26 weeks: OD	12
		Mesalamine at 26 weeks: >OD	10
	Kane^Citation26	Mesalamine: OD	12	26	USA	Adherence, medication consumption rates
		Mesalamine: >OD	10
	Connolly^Citation64,†	Mesalazine: OD	NR	NR	UK	Cost (total and direct), ICER, QALY
		Mesalazine: BID	NR

Notes:

* Primary outcome;

† economic study.

Abbreviations: ART, anti-retroviral therapy; BID, twice daily; HAART, highly active antiretroviral therapy; HIV/AIDS, human imunodeficiency virus/acquired immunodeficiency syndrome; ICER, incremental cost effectiveness ratio; ISMN, isosorbide mononitrate nitroglycerin; MEMS, medication event monitoring system; MPR, medication possession ratio; NR, not reported; OD, once daily; QID, four-times daily; SR, sustained release; TID, three times daily; QALY, quality-adjusted life year; XL, extended release.

Figure 2 Forest plot of the odds ratios and 95% CIs for adherence rates associated with dosing schedules (once daily versus > once daily) of medications in all diseases.

Note: The broken line indicates overall effect relative to the comparator.
Abbreviations: BID, twice daily; CI, confidence interval; D + L, DerSimonian and Laird technique for meta-analysis; OD, once daily; OR, odds ratio; TID, three times daily; vs, versus; I², statistical heterogeneity.

Figure 3 Forest plot of the odds ratios and 95% CIs for compliance rates associated with dosing schedules (once daily versus > once daily) of medications in all diseases.

Note: The broken line indicates overall effect relative to the comparator.
Abbreviations: BID, twice daily; CI, confidence interval; D + L, DerSimonian and Laird technique for meta-analysis; OD, once daily; RTI, respiratory tract infections; TID, three times daily; vs, versus; OR, odds ratio; I², statistical heterogeneity.

Figure 4 Forest plot of the odds ratios and 95% CIs for persistence rates associated with OD versus BID dosing schedules of medications in all diseases.

Note: The broken line indicates overall effect relative to the comparator.
Abbreviations: ACS, acute coronary syndrome; BID, twice daily; CI, confidence interval; D + L, DerSimonian and Laird technique for meta-analysis; OD, once daily; vs, versus; OR, odds ratio; I², statistical heterogeneity.

Table 3 Random effects meta-analyses for association of adherence/compliance/persistence to dosing schedules of medications in various chronic disorders

Disease	Dose comparison	OR (95% CI); P-value; heterogeneity
Adherence
Depression	OD vs BID	3.10 (2.15–4.47); P < 0.001; I^2 = 82.9%
Ulcerative colitis	OD vs >OD	3.20 (0.78–13.14); P = 0.107; I^2 = 39.4%
	OD vs BID	3.48 (1.32–9.17); P = 0.012; I^2 = 64.4%
HIV/AIDS	OD vs TID	3.48 (1.36–8.90); P = 0.009; I^2 = 0%
	BID vs TID	1.38 (0.87–2.17); P = 0. 167; I^2 = 0%
Across all the diseases	OD vs BID	2.20 (1.09–4.41); P = 0.027; I^2 = 95.5%
Across all the diseases	BID vs TID	1.88 (0.85–4.13); P = 0.118; I^2 = 61.9%
Across all the diseases	OD vs >OD	3.07 (1.80–5.23); P < 0.001; I^2 = 91.3%
Compliance
Hypertension	OD vs BID	2.42 (1.33–4.40); P = 0.004; I^2 = 0%
Infections	OD vs BID	9.85 (1.96–49.43); P = 0.005; I^2 = 83.4%
Diabetes	OD vs >OD	2.24 (1.38–3.66); P = 0.001; I^2 = 0.0%
Across all the diseases	OD vs BID	4.08 (1.68–9.91); P = 0.002; I^2 = 73.4%
Across all the diseases	OD vs >OD	3.50 (1.73–7.08); P < 0.001; I^2 = 69.0%
Persistence
Cardiovascular disorders	OD vs BID	0.85 (0.65–1.11); P = 0.235; I^2 = N/A
Across all the diseases	OD vs BID	1.43 (0.62–3.29); P = 0.405; I^2 = 96.9%

Abbreviations: AIDS, acquired immunodeficiency syndrome; BID, twice daily; CI, confidence interval; HIV, human immunodeficiency virus; I², statistical heterogeneity; N/A, not applicable; OD, once daily; OR, odds ratio; TID, three times daily; vs, versus.

Table 4 Studies presenting data on costs associated with adherence or compliance

Study	Disease	Type of evaluation	Results	Study conclusion
Brown^Citation46	Angina	Decision-analytic model	• Estimated total NHS annual cost for ISMN OD management: GB £248 • Estimated total NHS annual cost for ISMN OD management: GB £250	• Fewer health service resources were consumed by patients treated on OD regimen, with a higher compliance rate, compared to a BID regimen
Sidhu^Citation9	Renal transplant	Budget impact analysis	• Once daily tacrolimus yielded cumulative cost savings of GB £104,534	• Use of OD therapy could yield cost savings over five years in comparison to BID therapy of tacrolimus
Abecassis^Citation61	Renal transplant	Cost-effectiveness analysis	• Total direct cost with OD therapy: US$228,734 • Total direct cost with BID therapy: US$238,144	• Tacrolimus OD resulted in a reduction of costs relative to BID tacrolimus • Tacrolimus OD was the dominant therapy in the cost-effectiveness analysis

Note: 1 GBP = 1.5 USD.

Abbreviations: BID, twice daily; ISMN, isosorbide mononitrate nitroglycerin; OD, once daily dosing; NHS, UK National Health Service.

Appendix Study protocol listing the eligibility criteria for inclusion/exclusion of studies in the review as per the PRISMA guidelines

	Clinical effectiveness	Rationale
Inclusion criteria	Population	The population of interest to the review includes patients of any age, race, and gender receiving any oral medication for any chronic disease
	• Age: Adults (≥ 18 years)
	• Gender: Any
	• Race: Any
	• Qualifying event/disease/factors: Any chronic disease
	Intervention	The review aimed to compare adherence/compliance/ persistence associated with different dosing regimens rather than any particular intervention
	• Any oral intervention administered as OD, BID, TID, QID
	Comparator	The comparator of interest was a different dosage regimen of the interventions being evaluated in the study. Since the review required direct evidence on adherence of dosing regimens of interventions, placebo/best supportive care (BSC) as comparators were not included
	• Any oral intervention administered as OD, BID, TID, QID
	Study design	Observational studies and economic evidence were the best source of adherence/compliance data as they reflect ‘real life’ and were considered for the review.
	• Comparative cohort studies/longitudinal studies (retrospective)
	• Comparative cohort studies/longitudinal studies (prospective)
	• Published database analyses/registries
	• Case-control studies
	• Cross-sectional study—comparative
	• Randomized controlled trials
	• Non-randomized controlled trials
	• Economic studies
	Language restrictions	Studies with the full-text publication in English only were included in this review
	• English only
	Publication timeframe	No date restriction was applied in order to capture the maximum amount of adherence data
	• No date restriction for database searches
Exclusion criteria	Outcome of interest	Only studies reporting data pertaining to adherence/ compliance/persistence and healthcare costs associated with non-adherence were included in the review
	• Studies that did not report the outcomes of interest (adherence/ compliance/persistence and healthcare costs associated with non-adherence) were excluded from the review
	Route of administration	Studies assessing interventions administered only through an oral route were included in the current review
	• Studies evaluating interventions administered via a non-oral route were excluded

Abbreviations: BID, twice daily; BSC, best supportive care; OD, once daily; QID, four times daily; TID, three times daily.

CelisHStaessenJFagardRThijsLAmeryADoes isradipine modified release 5 mg once daily reduce blood pressure for 24 hours?J Cardiovasc Pharmacol19932223003047692173

 PubMed Web of Science ®Google Scholar

BairdMGBentley-TaylorMMCarruthersSGA study of efficacy, tolerance and compliance of once-daily versus twice-daily metoprolol (Betaloc) in hypertension. Betaloc Compliance Canadian Cooperative Study GroupClin Invest Med198472951026380858

 PubMed Web of Science ®Google Scholar

MaroEELwakatareJMedication compliance among Tanzanian hypertensivesEast Afr Med J19977495395429487426

 PubMed Web of Science ®Google Scholar

TurkiAKSulaimanSASAdherence to antihypertensive therapy in general hospital of Penang: does daily dose frequency matter?Jordan J Pharm Sci20092167175

 Google Scholar

GirvinBMcDermottBJJohnstonGDA comparison of enalapril 20 mg once daily versus 10 mg twice daily in terms of blood pressure lowering and patient complianceJ Hypertens199917111627163110608477

 PubMed Web of Science ®Google Scholar

AndrejakMGenesNVaurLPonceletPClersonPCarreAElectronic pill-boxes in the evaluation of antihypertensive treatment compliance: comparison of once daily versus twice daily regimenAm J Hypertens200013218419010701819

 PubMed Web of Science ®Google Scholar

BoisselJPMeillardOPerrin-FayolleEComparison between a bid and a tid regimen: improved compliance with no improved antihypertensive effect. The EOL Research GroupEur J Clin Pharmacol1996501–263678739813

 PubMed Web of Science ®Google Scholar

BrownREKendallMJHalpernMTCost analysis of once-daily ISMN versus twice-daily ISMN or transdermal patch for nitrate prophylaxisJ Clin Pharm Ther199722167769292406

 PubMed Web of Science ®Google Scholar

KardasPCompliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trialVasc Health Risk Manag20073223524217580734

 PubMedGoogle Scholar

BaeJPAndersonJZagarAThe effects of dosing complexity on adherence with prescription medications commonly used for cardiovascular patients [abstract]Value Health2010A360

 Google Scholar

SongXSanderSVarkerHAminAPatterns and predictors of persistence of warfarin and other commonly-utilized chronic medications among patients with atrial fibrillation [abstract]Value Health201013A170

 Web of Science ®Google Scholar

HessGBhandaryDFonsecaEAdherence to medications with once-a-day (qd) and twice-a-day (bid) dosing formulations in acute coronary syndrome (ACS) patients [abstract]Value Health201114A44

 Web of Science ®Google Scholar

DoeschAOMuellerSKonstandinMIncreased adherence after switch from twice daily calcineurin inhibitor based treatment to once daily modified released tacrolimus in heart transplantation: a pre-experimental studyTransplant Proc201042104238424221168673

 PubMed Web of Science ®Google Scholar

McLaughlinTHogueSLStangPEOnce-daily bupropion associated with improved patient adherence compared with twice-daily bupropion in treatment of depressionAm J Ther200714222122517414593

 PubMedGoogle Scholar

GrangerALFehnelSEHogueSLBennettLEdinHMAn assessment of patient preference and adherence to treatment with Wellbutrin SR: a web-based surveyJ Affect Disord2006902–321722116360216

 PubMed Web of Science ®Google Scholar

StangPSuppapanayaNHogueSLParkDRigneyUPersistence with once-daily versus twice-daily bupropion for the treatment of depression in a large managed-care populationAm J Ther200714324124617515697

 PubMedGoogle Scholar

StangPYoungSHogueSBetter patient persistence with once-daily bupropion compared with twice-daily bupropionAm J Ther2007141202417303971

 PubMedGoogle Scholar

PfeifferPNGanoczyDValensteinMDosing frequency and adherence to antipsychotic medicationsPsychiatr Serv200859101207121018832509

 PubMed Web of Science ®Google Scholar

CramerJAMattsonRHPreveyMLScheyerRDOuelletteVLHow often is medication taken as prescribed? A novel assessment techniqueJAMA198926122327332772716163

 PubMed Web of Science ®Google Scholar

CarlosFRamirezJGalindo-SuarezRMDuenasHPDB33 Economic evaluation of three first-line medications in painful diabetic peripheral neuropathy in MexicoValue in Health2010133A60

 Web of Science ®Google Scholar

MullenersWMWhitmarshTESteinerTJNoncompliance may render migraine prophylaxis useless, but once-daily regimens are betterCephalalgia199818152569601625

 PubMed Web of Science ®Google Scholar

WinklerATeuscherAUMuellerBDiemPMonotoring adherence to prescribed medication in type 2 diabetic patients treated with sulfonylureasSwiss Med Wkly200213227–2837938512428192

 PubMed Web of Science ®Google Scholar

DeziiCMKawabataHTranMEffects of once-daily and twice-daily dosing on adherence with prescribed glipizide oral therapy for type 2 diabetesSouth Med J2002951687111827247

 PubMed Web of Science ®Google Scholar

KardasPThe DIACOM study (effect of DosIng frequency of oral Antidiabetic agents on the COMpliance and biochemical control of type 2 diabetes)Diabetes Obes Metab20057672272816219016

 PubMed Web of Science ®Google Scholar

PullarTBirtwellAJWilesPGHayAFeelyMPUse of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times dailyClin Pharmacol Ther19884455405453180635

 PubMed Web of Science ®Google Scholar

CharpentierGFleuryFDubrocaIVaurLClersonPElectronic pill-boxes in the evaluation of oral hypoglycemic agent complianceDiabetes Metab200531218919515959425

 PubMed Web of Science ®Google Scholar

CarrieriMPLeportCProtopopescuCFactors associated with nonadherence to highly active antiretroviral therapy: a 5-year follow-up analysis with correction for the bias induced by missing data in the treatment maintenance phaseJ Acquir Immune Defic Syndr200641447748516652057

 PubMed Web of Science ®Google Scholar

NegredoEMoltoJMunoz-MorenoJASafety and efficacy of once-daily didanosine, tenofovir and nevirapine as a simplification antiretroviral approachAntivir Ther20049333534215259896

 PubMed Web of Science ®Google Scholar

StoneVEHoganJWSchumanPAntiretroviral regimen complexity, self-reported adherence, and HIV patients’ understanding of their regimens: survey of women in the her studyJ Acquir Immune Defic Syndr200128212413111588505

 PubMed Web of Science ®Google Scholar

AbellanJGarroteMPulidoFRubioRCostaJREvaluation of adherence to a triple antiretroviral therapy in HIV-positive patientsEur J Intern Med1999104202205

 Google Scholar

Echarri MartinezLERodriguez GonzalezCGCastillo RomeraIEvolution of adherence to antiretroviral treatment in a Spanish hospital during 2001, 2005, and 2008Lat Am J Pharm20113011731178

 Web of Science ®Google Scholar

MoyleGThe Assessing Patients’ Preferred Treatments (APPT-1) studyInt J STD AIDS200314Suppl 1343614617402

 PubMed Web of Science ®Google Scholar

KardasPOnce-daily dosage secures better compliance with antibiotic therapy of respiratory tract infections than twice daily dosageJ Appl Res200332201206

 Google Scholar

KardasPComparison of patient compliance with once-daily and twice-daily antibiotic regimens in respiratory tract infections: results of a randomized trialJ Antimicrob Chemother200759353153617289766

 PubMed Web of Science ®Google Scholar

SpiritusEMChangRJZhangJXCost savings of clarithromycin compared with erythromycin or cefaclor in the treatment of lower respiratory tract infection: Results of a randomized, multicenter studyAm J Manag Care19984Suppl 11S562S570

 Google Scholar

RazRElchananGColodnerRPenicillin V twice daily vs four times daily in the treatment of streptococcal pharyngitisInfect Dis Clin Pract1995415054

 Web of Science ®Google Scholar

AbecassisMMSeifeldinRRiordanMEPatient outcomes and economics of once-daily tacrolimus in renal transplant patients: results of a modeling analysisTransplant Proc20084051443144518589126

 PubMed Web of Science ®Google Scholar

SidhuMLeesLWarnerJFive-year budget impact analysis of once-daily versus twice-daily tacrolimus, in patients undergoing renal transplant in the United Kingdom [abstract]Value Health201013A170

 Web of Science ®Google Scholar

EberlinMBKramerIEvaluation of medication compliance of liver transplant patients switched from a twice-daily to a once-daily tacrolimus-based regimen [abstract]Pharm World Sci20103267067120717844

 PubMedGoogle Scholar

HawthorneABStensonRGillespieDOnce daily mesalazine as maintenance therapy for ulcerative colitis (UC): a one-year single-blind randomized trial [abstract]Gastroenterology2011140SupplS65

 Google Scholar

LachaineJBeaucheminCYenLHodgkinsPMedication adherence and persistence in the treatment of ulcerative colitis analyses with the RAMQ database [abstract]Can J Gastroenterol201125Suppl A Abstract A072

 Google Scholar

KaneSHuoDMagnantiKA pilot feasibility study of once daily versus conventional dosing mesalamine for maintenance of ulcerative colitisClin Gastroenterol Hepatol20031317017315017487

 PubMed Web of Science ®Google Scholar

ConnollyMPNielsenSKCurrieCJPooleCDTravisSPAn economic evaluation comparing once daily with twice daily mesalazine for maintaining remission based on results from a randomised controlled clinical trialJ Crohns Colitis200931323721172245

 PubMed Web of Science ®Google Scholar

JackeviciusCAMamdaniMTuJVAdherence with statin therapy in elderly patients with and without acute coronary syndromesJAMA2002288446246712132976

 PubMed Web of Science ®Google Scholar