Article Research| Volume 65, ISSUE 4, P464-476, July 2017

Pillbox intervention fidelity in medication adherence research: A systematic review

Published:January 14, 2017DOI:


      • Significant limitations exist in reports of pillboxes in adherence interventions.
      • Pillbox study translation to practice should rely on reported, not assumed intervention components.
      • It is important to assess how control groups adhere to the control condition.
      • Receiving or enacting treatments is as important as reporting attrition.
      • The five components of intervention fidelity are underreported in pillbox studies.
      • It is unclear how to best enact pillboxes to support medication adherence behaviors.



      Pillboxes are widely available, have evidence of effectiveness, but translating pillboxes in self-management interventions requires an understanding of intervention components.


      To review components of intervention design, interventionist training, delivery, receipt, enactment, and targeted behaviors in adherence studies.


      Five multidisciplinary databases were searched to find reports of controlled trials testing pillboxes and medication adherence interventions in adults managing medications. Details of treatment fidelity, that is, design, training, delivery, receipt, and enactment, were abstracted.


      A total of 38 articles reporting 40 studies were included. Treatment fidelity descriptions were often lacking, especially reporting receipt and enactment, important for both control and intervention groups. Clearly reported details are needed to avoid making assumptions when translating evidence.


      These findings serve as a call to action to explicitly state intervention details. Lack of reported intervention detail is a barrier to translating which components of pillboxes work in influencing medication adherence behaviors and outcomes.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Nursing Outlook
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ascione F.J.
        • Shimp L.A.
        The effectiveness of four education strategies in the elderly.
        Drug Intelligence & Clinical Pharmacy. 1984; 18: 926-931
        • Bailey S.C.
        • Oramasionwu C.U.
        • Wolf M.S.
        Rethinking adherence: A health literacy-informed model of medication self-management.
        Journal of Health Communication. 2013; 18: 20-30
        • Begg C.
        • Cho M.
        • Eastwood S.
        • Horton R.
        • Moher D.
        • Olkin I.
        • Simel D.
        Improving the quality of reporting of randomized controlled trials: The CONSORT statement.
        JAMA. 1996; 276: 637-639
        • Boeni F.
        • Spinatsch E.
        • Suter K.
        • Hersberger K.E.
        • Arnet I.
        Effect of drug reminder packaging on medication adherence: A systematic review revealing research gaps.
        Systematic Reviews. 2014; 3: 29
        • Borrelli B.
        • Sepinwall D.
        • Ernst D.
        • Bellg A.J.
        • Czajkowski S.
        • Breger R.
        • Ogedegbe G.
        A new tool to assess treatment fidelity and evaluation of treatment fidelity across 10 years of health behavior research.
        Journal of Consulting and Clinical Psychology. 2005; 73: 852
        • Bosworth H.B.
        • Olsen M.K.
        • Neary A.
        • Orr M.
        • Grubber J.
        • Svetkey L.
        • Oddone E.Z.
        Take Control of Your Blood pressure (TCYB) study: A multifactorial tailored behavioral and educational intervention for achieving blood pressure control.
        Patient Education and Counseling. 2008; 70: 338-347
        • Burrelle T.N.
        Evaluation of an interdisciplinary compliance service for elderly hypertensives.
        Journal of Geriatric Drug Therapy. 1986; 1: 23-51
        • Calvert S.B.
        • Kramer J.M.
        • Anstrom K.J.
        • Kaltenbach L.A.
        • Stafford J.A.
        • LaPointe N.M.A.
        Patient-focused intervention to improve long-term adherence to evidence-based medications: A randomized trial.
        American Heart Journal. 2012; 163: 657-665.e1
        • Conn V.S.
        • Ruppar T.M.
        • Chan K.C.
        • Dunbar-Jacob J.
        • Pepper G.A.
        • De Geest S.
        Packaging interventions to increase medication adherence: Systematic review and meta-analysis.
        Current Medical Research and Opinion. 2015; 31: 145-160
        • Crome P.
        • Akehurst M.
        • Keet J.
        Drug compliance in elderly hospital in-patients. Trial of the Dosett box.
        The Practitioner. 1980; 224: 782-785
        • Fairley C.K.
        • Levy R.
        • Rayner C.R.
        • Allardice K.
        • Costello K.
        • Thomas C.
        • Mijch A.
        Randomized trial of an adherence programme for clients with HIV.
        International Journal of STD & AIDS. 2003; 14: 805-809
        • Farsaei S.
        • Sabzghabaee A.M.
        • Zargarzadeh A.H.
        • Amini M.
        Effect of pharmacist-led patient education on glycemic control of type 2 diabetes: A randomized controlled trial.
        Journal of Research in Medical Sciences. 2011; 16: 43-49
        • Goldstein C.M.
        • Gathright E.C.
        • Dolansky M.A.
        • Gunstad J.
        • Sterns A.
        • Redle J.D.
        • Hughes J.W.
        Randomized controlled feasibility trial of two telemedicine medication reminder systems for older adults with heart failure.
        Journal of Telemedicine & Telecare. 2014; 20: 293-299
        • Goujard C.
        • Bernard N.
        • Sohier N.
        • Peyramond D.
        • Lançon F.
        • Chwalow J.
        • Delfraissy J.-F.
        Impact of a patient education program on adherence to HIV medication.
        Journal of Acquired Immune Deficiency Syndromes. 2003; 34: 191-194
        • Higashi K.
        • Medic G.
        • Littlewood K.J.
        • Diez T.
        • Granström O.
        • De Hert M.
        Medication adherence in schizophrenia: Factors influencing adherence and consequences of nonadherence, a systematic literature review.
        Therapeutic Advances in Psychopharmacology. 2013; 3: 200-218
        • Huang H.Y.
        • Maguire M.G.
        • Miller 3rd, E.R.
        • Appel L.J.
        Impact of pill organizers and blister packs on adherence to pill taking in two vitamin supplementation trials.
        American Journal of Epidemiology. 2000; 152: 780-787
        • Jafar T.H.
        • Stark P.C.
        • Schmid C.H.
        • Landa M.
        • Maschio G.
        • de Jong P.E.
        • Levey A.S.
        Progression of chronic kidney disease: The role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: A patient-level meta-analysis.
        Annals of Internal Medicine. 2003; 139: 244-252
        • Jonsdottir H.
        • Opjordsmoen S.
        • Birkenaes A.
        • Simonsen C.
        • Engh J.
        • Ringen P.
        • Andreassen O.
        Predictors of medication adherence in patients with schizophrenia and bipolar disorder.
        Acta Psychiatrica Scandinavica. 2013; 127: 23-33
        • Kalichman S.C.
        • Kalichman M.O.
        • Cherry C.
        • Swetzes C.
        • Amaral C.M.
        • White D.
        • Eaton L.
        Brief behavioral self-regulation counseling for HIV treatment adherence delivered by cell phone: An initial test of concept trial.
        AIDS Patient Care and STDs. 2011; 25: 303-310
      1. Kennedy, L. M. (1990). The effectiveness of a self-care medication education protocol on the home medication behaviors of recently hospitalized elderly. PhD thesis. The University of Texas at Austin, TX, USA.

        • Kripalani S.
        • Roumie C.L.
        • Dalal A.K.
        • Cawthon C.
        • Businger A.
        • Eden S.K.
        • Theobald C.
        Effect of a pharmacist intervention on clinically important medication errors after hospital discharge: A randomized trial.
        Annals of Internal Medicine. 2012; 157: 1-10
        • Laramee A.S.
        • Levinsky S.K.
        • Sargent J.
        • Ross R.
        • Callas P.
        Case management in a heterogeneous congestive heart failure population: A randomized controlled trial.
        Archives of Internal Medicine. 2003; 163: 809-817
        • Lee M.
        • Kemp J.A.
        • Canning A.
        • Egan C.
        • Tataronis G.
        • Farraye F.A.
        A randomized controlled trial of an enhanced patient compliance program for Helicobacter pylori therapy.
        Archives of Internal Medicine. 1999; 159: 2312-2316
        • Levensky E.R.
        Further development and evaluation of an individualized intervention for increasing adherence to HIV medications.
        University of Nevada, Reno, NV2006
        • Littenberg B.
        • MacLean C.D.
        • Hurowitz L.
        The use of adherence aids by adults with diabetes: A cross-sectional survey.
        BMC Family Practice. 2006; 7: 1
        • Macdonald E.T.
        • MacDonald J.
        • Phoenix M.
        Improving drug compliance after hospital discharge.
        British Medical Journal. 1977; 2: 618-621
        • Macintosh P.
        • Pond G.
        • Pond B.
        • Leung V.
        • Siu L.
        A comparison of patient adherence and preference of packaging method for oral anticancer agents using conventional pill bottles versus daily pill boxes.
        European Journal of Cancer Care. 2007; 16: 380-386
        • Maier C.
        • Mustapic D.
        • Schuster E.
        • Luger A.
        • Eher R.
        Effect of a pocket-size tablet-dispensing device on glycaemic control in type 2 diabetic patients.
        Diabetic Medicine. 2006; 23: 40-45
        • McPherson-Baker S.
        • Malow R.
        • Penedo F.
        • Jones D.L.
        • Schneiderman N.
        • Klimas N.
        Enhancing adherence to combination antiretroviral therapy in non-adherent HIV-positive men.
        AIDS Care. 2000; 12: 399-404
        • Miaskowski C.
        • Dodd M.
        • West C.
        • Schumacher K.
        • Paul S.M.
        • Tripathy D.
        • Koo P.
        Randomized clinical trial of the effectiveness of a self-care intervention to improve cancer pain management.
        Journal of Clinical Oncology. 2004; 22: 1713-1720
        • Morello C.M.
        • Chynoweth M.
        • Kim H.
        • Singh R.F.
        • Hirsch J.D.
        Strategies to improve medication adherence reported by diabetes patients and caregivers: Results of a taking control of your diabetes survey.
        Annals of Pharmacotherapy. 2011; 45: 145-153
        • Moshkovska T.
        • Stone M.A.
        • Smith R.M.
        • Bankart J.
        • Baker R.
        • Mayberry J.F.
        Impact of a tailored patient preference intervention in adherence to 5-aminosalicylic acid medication in ulcerative colitis: Results from an exploratory randomized controlled trial.
        Inflammatory Bowel Diseases. 2011; 17: 1874-1881
        • Murray M.D.
        • Birt J.A.
        • Manatunga A.K.
        • Darnell J.C.
        Medication compliance in elderly outpatients using twice-daily dosing and unit-of-use packaging.
        The Annals of Pharmacotherapy. 1993; 27: 616-621
        • Nochowitz B.
        • Shapiro N.L.
        • Nutescu E.A.
        • Cavallari L.H.
        Effect of a warfarin adherence aid on anticoagulation control in an inner-city anticoagulation clinic population.
        The Annals of Pharmacotherapy. 2009; 43: 1165-1172
        • Park D.C.
        • Morrell R.W.
        • Frieske D.
        • Kincaid D.
        Medication adherence behaviors in older adults: Effects of external cognitive supports.
        Psychology and Aging. 1992; 7: 252-256
        • Peterson G.M.
        • McLean S.
        • Millingen K.S.
        A randomised trial of strategies to improve patient compliance with anticonvulsant therapy.
        Epilepsia. 1984; 25: 412-417
        • Porter A.K.
        • Taylor S.R.
        • Yabut A.H.
        • Al-Achi A.
        Impact of a pill box clinic to improve systolic blood pressure in veterans with uncontrolled hypertension taking 3 or more antihypertensive medications.
        Journal of Managed Care & Specialty Pharmacy. 2014; 20: 905-911
        • Rehder T.L.
        • McCoy L.K.
        • Blackwell B.
        • Whitehead W.
        • Robinson A.
        Improving medication compliance by counseling and special prescription container.
        American Journal of Hospital Pharmacy. 1980; 37: 379-385
        • Ruggenenti P.
        • Perna A.
        • Gherardi G.
        • Gaspari F.
        • Benini R.
        • Remuzzi G.
        Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy.
        The Lancet. 1998; 352: 1252-1256
        • Schmidt S.
        • Sheikzadeh S.
        • Beil B.
        • Patten M.
        • Stettin J.
        Acceptance of telemonitoring to enhance medication compliance in patients with chronic heart failure.
        Telemedicine and e-Health. 2008; 14: 426-433
        • Suárez-Varela M.T.M.
        Study on the use of a smart pillbox to improve treatment compliance.
        Atencion Primaria/Sociedad Espanola de Medicina de Familia y Comunitaria. 2009; 41: 185-191
        • Suppapitiporn S.
        • Chindavijak B.
        • Onsanit S.
        Effect of diabetes drug counseling by pharmacist, diabetic disease booklet and special medication containers on glycemic control of type 2 diabetes mellitus: A randomized controlled trial.
        Journal-Medical Association of Thailand. 2005; 88: S134-S141
        • Sweeney S.
        • Dixon J.
        • Sutcliffe I.
        The impact of the clinical pharmacist on compliance in a geriatric population.
        Pharmaceutical Journal. 1989; 242: R4-R6
        • Taylor C.T.
        • Byrd D.C.
        • Krueger K.
        Improving primary care in rural Alabama with a pharmacy initiative.
        American Journal of Health System Pharmacy. 2003; 60: 1123-1129
        • Traiger G.
        • Bui L.
        A self-medication administration program for transplant recipients.
        Critical Care Nurse. 1997; 17: 71-79
        • Tsuyuki R.T.
        • Fradette M.
        • Johnson J.A.
        • Bungard T.J.
        • Eurich D.T.
        • Ashton T.
        • Mackay E.
        A multicenter disease management program for hospitalized patients with heart failure.
        Journal of Cardiac Failure. 2004; 10: 473-480
        • Viswanathan M.
        • Golin C.E.
        • Jones C.D.
        • Ashok M.
        • Blalock S.J.
        • Wines R.C.
        • Lohr K.N.
        Interventions to improve adherence to self-administered medications for chronic diseases in the United States: A systematic review.
        Annals of Internal Medicine. 2012; 157: 785-795
        • Vrijens B.
        • De Geest S.
        • Hughes D.A.
        • Przemyslaw K.
        • Demonceau J.
        • Ruppar T.
        • Lewek P.
        A new taxonomy for describing and defining adherence to medications.
        British Journal of Clinical Pharmacology. 2012; 73: 691-705
        • Wang H.
        • Zhou J.
        • Huang L.
        • Li X.
        • Fennie K.P.
        • Williams A.B.
        Effects of nurse-delivered home visits combined with telephone calls on medication adherence and quality of life in HIV-infected heroin users in Hunan of China.
        Journal of Clinical Nursing. 2010; 19: 380-388
        • Ward B.W.
        • Schiller J.S.
        • Goodman R.A.
        Multiple chronic conditions among US adults: A 2012 update.
        Preventing Chronic Disease. 2014; 11: 130389
        • Winland-Brown J.
        • Valiante J.
        Effectiveness of different medication management approaches on elders' medication adherence.
        Outcomes Management for Nursing Practice. 2000; 4: 172-176
        • Zedler B.K.
        • Kakad P.
        • Colilla S.
        • Murrelle L.
        • Shah N.R.
        Does packaging with a calendar feature improve adherence to self-administered medication for long-term use? A systematic review.
        Clinical Therapeutics. 2011; 33: 62-73
        • Zillich A.J.
        • Sutherland J.M.
        • Kumbera P.A.
        • Carter B.L.
        Hypertension outcomes through blood pressure monitoring and evaluation by pharmacists (HOME study).
        Journal of General Internal Medicine. 2005; 20: 1091-1096