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Table 1 Description of studies

From: Interventions to increase adherence in patients taking immunosuppressive drugs after kidney transplantation: a systematic review of controlled trials

Author, year Study design Included patients/analyzed patients (I, C) Setting and region Patient characteristics (intervention/control or whole population) Medication (dosing frequency) Intervention Control Intervention period; observation period
Annunziato 2015 Cohort study (retrospective chart review) Included n = 25
Analyzed n = 22 (12, 10)
Two pediatric and adult kidney transplant service; USA Age (mean, years) 21.68/21.03
Male 42%/40%
White 25%/0
African American 17/10
Hispanic 17%/70%
Asian 33%/0
Other race 8%/20%
Glomerular 64%/13%
Non-glomerular 36%/88%
Standard deviation of tacrolimus blood levels (mean) 1.98/2.42
NR Auspices of the transition coordinator
Identifying and addressing gaps in self-management
Discussing transfer process including fears and concerns with patient and patient’s family members
Solving identified problems with patient, patient’s family, and team members
Facilitating last appointment in pediatrics
Completing “transition checklist” during last visit in pediatrics
Providing patient and patient’s family with information about their soon-to-be adult providers
Sharing impressions with members of adult team
Standard care 1 year; 1 year
Breu-Dejean 2016 RCT Included n = 110 (55, 55)
Analyzed n = NR (12, 10)
Outpatient
clinic at Toulouse University Hospital; Toulouse,
France
Age (mean, years) 49.7/47.9
Number of immunosuppressants (mean) 2.8/2.7
Male 56.4%/49.1%
Single 27.3%/34.5%
Adherence score at first evaluation (mean) 29.9/32.0
Cyclosporine (dosing NR),
Sirolimus (dosing NR),
Tacrolimus (dosing NR),
Mycophenolate mofetil (dosing NR),
Enteric-coated mycophenolate sodium (dosing NR),
Prednisone (dosing NR),
Azathioprine,
Everolimus (dosing NR)
Psychoeducational intervention (every week)
Conducted by a multidisciplinary team
that included 1 physician, 1 psychologist, 2 nurses, 1 kinesiotherapist, 1 dietician, and 1 social worker
Main objectives: to provide information about disease and to translate this information into a form that enabled to gain increased competence during normal daily life
Standard care 8 weeks; 10 years
Chisholm 2001 RCT Randomized n = 24 (12, 12)
Analyzed n = 24 (12, 12)
Medical College of Georgia (MCG) Hospital and Clinics in Augusta, Georgia, USA Age (mean, years) 49.2 (10.2)
Male 75%
Caucasian 58.3%
African–American 37.5%
Hispanic 4.2%
Cyclosporine (dosing NR)
Tacrolimus (dosing NR)
Clinical pharmacy services
Medication histories and reviews (monthly)
Clinical pharmacist: counseling patients (verbally/written) concerning medications, recommendations to nephrologists, contact number given to patients
Assessment of patient understanding of medication therapy
Clinical pharmacist-patient interaction by telephone, if patient had no clinic visit within 1 month
Routine clinic services 1 year; 1 year
Chisholm 2013 RCT Randomized n = 150
(76, 74)
Analyzed n = 150
(76, 74)
Southwest USA; Avella Specialty Pharmacy Age (mean, years) 52.78/51.32 Annual income (mean, $) 39,673.96/28,290.44
Males 56.6%/55.4%
White 77.6%/82.4%
African–Americans 15.8%/14.9%
Hispanic 71.1%/68.9%
Married 40.8%/48.6%
Cyclosporine (dosing NR)
Tacrolimus (dosing NR)
Standard specialty pharmacy care
+ Individual behavioral adherence contracts (goal setting, motivation, social support, memory techniques, problem-solving, consequences of non-adherence) discussed with pharmacist every 3 months to discuss new goals etc.
Standard specialty pharmacy care
Mail or telephone reminders of monthly medication refills and an adherence ‘packet’ consisting of adherence-focused educational pamphlets and a pillbox
1 year; 1 year
De Geest 2006 (Pilot) RCT Randomized n = 18 (6, 12)
Analyzed n = 13 (4, 9)
University Hospital Basel, Switzerland and Cantonal Hospital, Aarau, Switzerland Non-adherent renal transplant recipients (identified in a previous study)
Age (mean, years) 45.6
Male 78.6%
Cyclosporine, Mycophenolae-Mofetil, Tacrolimus, Sirolimus (dosing: twice daily)
Azathioprin/Prednisone (dosing: once daily)
Enhanced usual care
1 home visit with assessment of reasons for adherence using EM printouts and tailored and individualized (behavioral, educational, and social support) interventions
+ 3 monthly telephone interviews (EM printouts for problem detection, feedback and proxy goal setting)
Enhanced usual care
Treating physicians were informed if their patients were identified as being non-adherent or if a moderate or severe depression or suicidal ideation was suggested
3 months; 9 months
Fennell 1994 Non-randomized trial (matched according to age and sex) Included n = 29 (14, 15)
Analyzed n = NR
University of Florida; USA Age (mean, years) 12.0
Male 59%
European-Amerikan 72%
African- or Latino-American 28%
NR Family-based program
Educational booklet with information about transplantation;
Peer modeling videotape (with discussions about the need for compliance, benefits of a kidney transplant, and strategies for remembering to take medications)
Medication calendar to record medication compliance
Weekly rewards to the children from their parents
Usual care NR; NR
Garcia 2015 RCT Included n = 111 (55, 56)
Analyzed n = 111 (55, 56)
Universidade Estadual
Paulista; Botucatu; Brasil
Age (mean, years) 46.0/49.3
Male 56.4%/62.5%
Tacrolimus (dosing NR), Cyclosporine (dosing NR), Mycophenolate (dosing NR), Azathioprine (dosing NR), Prednisone (dosing NR) Usual care
Education/counseling sessions aimed at improving delivered by a single healthcare professional with expertise in renal transplantation (10 weekly sessions, 30 min each); diverse topics which included information about the importance of taking immunosuppressive drugs even when the graft function is normal, using a non-judgmental
approach to discussing adherence and tools to integrate medication intake with the patient’s daily routine
Usual transplant
patient education by the medical team regarding the immunosuppressant
drugs in their first outpatient assessment after discharge
3 months; 1 year
Hardstaff 2003 RCT Randomized n = 75
Analyzed at first outpatient visit: n = 48 (23, 25)
Analyzed at period after feedback: n = 40 (20, 20)
NR Stable (>1 year post-transplant) renal transplant patients Prednisolone/Azathioprine (dosing: once daily) Feedback about self-medication behavior at first outpatient clinic visit Usual care Unique at first outpatient visit (2–6 months); 4–12 months (depending on first outpatient visit)
Henriksson 2016 RCT Included n = 80 (40, 40)
Analyzed n = 80 (40, 40)
Karolinska University Hospital; Stockholm, Sweden Age (mean) 44.3/45.0
Male 27/25
Tacrolimus (dosing: twice daily, or in “slow release” form once daily), cyclosporine (dosing: twice daily) Electronic medication dispenser (EMD)
Loaded with a week’s worth of medication at a time
At the prescribed time for taking the medication visual and audible signals
After signals this (or after the medication was taken), the EMD sent an SMS message to the web-based software, thus providing information about patient compliance
Provider reviewed medication history
Standard care 2 years; 1 year
Joost 2014 Non-concurrent cohort study Included n = 74
(39,35)
Analyzed n = 67 (35, 32)
Erlangen University Hospital, Germany Age (mean, years) 51/54
Male 77%/62
Married 83%/82%
Tacrolimus/Cyclosporin/Mycophenolic acid
(dosing: twice daily)
Intensified Care Group
Standard care
+ pharmaceutical care: ≥ 3 counseling sessions including educational, behavioral and technical interventions (during week 1–2), further counseling sessions during follow-up visits throughout the 12 months (≥ 1 quarterly; ≤ 1 monthly), encouraged to contact the pharmacist via phone or email
Standard Care Group
Handout explaining post-transplant medication
+ 1–2 individual standardized training sessions (during 1–2 week)
+ scheduled follow-up visits
12 months; standard care 2 weeks
Russel 2011 (Pilot) RCT Randomization n = 15 (8, 7)
Analyzed n = 13 (8, 5)
Tertiary care transplant centre; Midwestern USA Medication non-adherent (taking < 85% of doses before inclusion)
Age (mean, years) 12.1/15.7
Male 50%/43%
Caucasian 100%/57%
Education level (some high school/high school) 63%/14%
Married 75%/43%
Pillbox use 88%/29%
≥ 1 immunosuppressive medication (medication not specified; dosing: twice daily) Continuous self-improvement intervention
Identification of life routines, important people, and possible solutions to enhance medication taking
Individual monthly medication taking feedback
Focus on changing the systems in which the person lives using the plan-do-check-act process
Attention control intervention
Monthly educational brochures
Telephone calls to review the information and to ask participants whether they have any questions about the information
6 months; 6 months (plus prior 3 months adherence screening phase)
Tschida 2013 Cohort study (retrospective claims analysis) Before propensity score matching n = 1830
Propensity-matched sample n = 1038 (519 pairs)
Mandatory program for the commercial employers of UnitedHealthcare, USA UnitedHealthcare enrollees receiving pharmacy and medical benefits through UnitedHealthcare ≥ 1 prescriptions for an oral transplant study drug (dosing NR) Specialty pharmacy program
Extensive patient education materials
Monthly proactive adherence program: refill reminder, adherence screening, and if non-adherent interventions with members and physicians
Transplant clinical management program: telephonic patient education, assessment of clinical status, pharmaceutical care intervention
Contact number 24 h available
No intervention 1 year; 1 year after index date (the first immunosuppressive drug prescription fill date)
  1. NR not reported, RCT randomized controlled trial