A Pharmacist Led, Patient Tailored Intervention to Improve Immunosuppressant Medication Adherence in Nonadherent Kidney Transplant Patients
Phase: NA
Conditions: Medication Adherence, Kidney Transplantation
Sponsor: Imperial College London

Immunosuppressant medication nonadherence intervention study 
Version 10.0   31/10/2017 
 
IRAS Project ID 232623 
 
 
A pharmacist led, patient tailored intervention to improve 
immunosuppressant medication adherence in nonadherent 
kidney transplant patients 
 
 
 
Version 10 – 31/10/2017 
 
 
 
 
MAIN SPONSOR: Imperial College Healthcare NHS Trust  
FUNDERS:  Imperial Health Charity Fund 7089 
STUDY COORDINATION CENTRE: Imperial College Healthcare NHS Trust 
NRES reference: 18/LO/0032 
 
 
 
Protocol authorised by: 
 
Name & Role 
Date 
Signature 
Prof David Taube, Consultant Nephrologist 
23/6/17 
 
Mr Frank Dor, Consultant Transplant Surgeon and 
Head of Speciality, Transplantation 
23/6/17 
 
ICRTC Transplant Research and Audit Group 
23/6/17 
 
 
 
 
Study Management Group 
 
Chief Investigator:  
Dawn Goodall 
 
Co-investigators:  
Prof David Taube 
Dr Adam McLean 
Dr Michelle Willicombe 
 
 
Study Management:  
1. Project steering group (to include two patients)  
2. Imperial College Healthcare NHS Trust Transplant Research Group 
 
 

Immunosuppressant medication nonadherence intervention study 
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IRAS Project ID 232623 
Study Coordination Centre  
 
For general queries, supply of study documentation, and collection of data, please contact: 
 
Study Coordinator: Dawn Goodall 
Address: Renal and Transplant clinic 
 
 
 
Hammersmith Hospital, W12 0HS 
Tel: 0203 313 4247 
 
 
 
 
 
Mobile:  07962258199  
 
 
 
 
E-mail:  dawn.goodall1@nhs.net 
 
 
Clinical Queries 
 
Clinical queries should be directed to Dawn Goodall who will direct the query to the appropriate 
person 
 
 
Sponsor 
 
Imperial College Healthcare NHS Trust is the main research Sponsor for this study.  For further 
information regarding the sponsorship conditions, please contact the Head of Regulatory 
Compliance at: 
 
 
 
Joint Research Compliance Office 
Imperial College London & Imperial College Healthcare NHS Trust 
2nd Floor Medical School Building 
St Mary’s Hospital 
Praed Street 
London 
W2 1NY 
Tel: 020759 41862 
 
 
Funder 
 
Imperial College Healthcare NHS Trust 
 
This protocol describes the pharmacist led, patient tailored intervention to improve 
immunosuppressant medication adherence in nonadherent kidney transplant patients study and 
provides information about procedures for entering participants.  Every care was taken in its 
drafting, but corrections or amendments may be necessary. These will be circulated to investigators 
in the study.  Problems relating to this study should be referred, in the first instance, to the Chief 
Investigator.  
 
This study will adhere to the principles outlined in the NHS Research Governance Framework for 
Health and Social Care (2nd edition). It will be conducted in compliance with the protocol, the Data 
Protection Act and other regulatory requirements as appropriate.  
 
 
 

Immunosuppressant medication nonadherence intervention study 
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IRAS Project ID 232623 
Table of Contents 
 
1. 
INTRODUCTION 
6 
1.1 BACKGROUND 
6 
2.  STUDY OBJECTIVES 
7 
3.  STUDY DESIGN 
7 
3.1 STUDY OUTCOME MEASURES 
8 
4. 
PARTICIPANT ENTRY 
9 
4.1 PRE-REGISTRATION EVALUATIONS 
9 
4.2 INCLUSION CRITERIA 
9 
4.3 EXCLUSION CRITERIA 
9 
4.4 WITHDRAWAL CRITERIA 
10 
5. 
ADVERSE EVENTS 
10 
5.1 DEFINITIONS 
10 
5.3 REPORTING PROCEDURES 
10 
6. 
ASSESSMENT AND FOLLOW-UP 
11 
7. 
STATISTICS AND DATA ANALYSIS 
11 
8. 
REGULATORY ISSUES 
12 
8.1 ETHICS APPROVAL 
12 
8.2 CONSENT 
12 
8.3 CONFIDENTIALITY 
12 
8.4 INDEMNITY 
12 
8.5 SPONSOR 
12 
8.6 FUNDING 
13 
8.7 AUDITS AND INSPECTIONS 
13 
9. 
STUDY MANAGEMENT 
13 
11. 
PUBLICATION POLICY 
13 
12. 
REFERENCES 
ERROR! BOOKMARK NOT DEFINED. 
EXAMPLE APPENDICES 
13 
APPENDIX 1. 
SUMMARY OF INVESTIGATIONS, TREATMENT AND ASSESSMENTS 
13 
 
 
 

Immunosuppressant medication nonadherence intervention study 
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GLOSSARY OF ABBREVIATIONS 
ACR 
Acute cellular rejection 
AMR 
Antibody mediated rejection 
CNI 
Calcineurin inhibitor 
DNA 
Did not attend 
DSA 
Donor specific antibody 
eGFR 
Estimated Glomerular filtration rate 
IPV 
Intrapatient variability 
 
 
KEYWORDS 
Medication adherence 
Nonadherence 
Clinic attendance 
Intrapatient variability 
Tacrolimus 
Kidney transplant 
 
 
STUDY SUMMARY 
 
TITLE A pharmacist led, patient tailored intervention to improve immunosuppressant 
medication adherence in nonadherent kidney transplant patients 
DESIGN Prospective, multidimensional cohort study 
AIMS The aim of the study is to determine prospectively, whether patients who receive 
regular, intensive, pharmacist led, tailored medication adherence support will 
demonstrate an improved adherence to their medication regime resulting in a 
reduction in the observed intrapatient variability (IPV) of tacrolimus trough levels and 
improved attendance at out-patient clinic appointments 
OUTCOME MEASURES Difference in immunosuppression medication adherence before and after the 
intervention  
Difference in the median IPV before and after the intervention 
Difference in outpatient clinic nonattendance rate before and after the intervention 
POPULATION Adult kidney transplant patients 
ELIGIBILITY Kidney transplant patients with a high IPV of their tacrolimus levels  
DURATION One year 
 
 
 
 

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REFERENCE DIAGRAM 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Informed consent and enrol  
 
Intervention group 
Kidney transplant patients with an IPV of 
tacrolimus levels of greater than 18.15% in the 
previous 12 months 
Within 2 weeks of recruitment 
Medication history with pharmacist in clinic 
Formal assessment of medication adherence 
Identify specific barriers to adherence 
Agree individually tailored interventions 
Agree regular review as appropriate for the 
patient 
12 months 
Medication adherence assessed 
IPV tacrolimus levels 
Clinic attendance rate 
Secondary outcomes 
Identify and categorise patients 
Analysis 
3, 6 and 9 months 
Medication adherence assessment 

Immunosuppressant medication nonadherence intervention study 
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1. 
INTRODUCTION  
 
1.1 
BACKGROUND 
Organs for transplantation remain a scarce and precious resource with over 5000 patients currently 
on the kidney transplant waiting list. A kidney transplant costs approximately £17,000 in the first 
year and £5,000 per subsequent year. If the transplant fails, the patient must return to dialysis at an 
estimated cost of £30,800 per year or be retransplanted.  While short term outcomes have improved 
steadily over the last 15-20 years, longer term outcomes haven’t and after 10 years approximately 
30% of kidney transplants have failed.  
 
Nonadherence to immunosuppressive medication is increasingly being associated with these poor 
long term outcomes (1-10) as it has been shown to be a potent risk factor for the development of de 
novo donor specific antibody (DSA) and antibody mediated rejection (AMR) with AMR being a 
leading cause of kidney transplant failure(11-14). In a prospective study undertaken by Sellares et 
al(11) investigating the causes of kidney transplant failure in a series of patients who underwent an 
indicative biopsy it was shown that 64% of the transplants that failed were due to rejection, every 
rejection loss had evidence of AMR by the time of failure and among the rejection losses, 47% were 
independently identified by their clinician as being nonadherent. A study by Pinsky et al reported 
that not taking immunosuppressive medications as prescribed (defined as taking medication <95.1% 
of days) is associated with a 60% increased risk of kidney transplant failure(15). 
 
Studies have estimated that 30-50% of transplant patients are nonadherent to their 
immunosuppressive medication(1, 4, 6, 16) and that graft loss is seven times more likely in a 
nonadherent compared to an adherent patient(17). Nonadherence to immunosuppression can start 
at any time after the transplant; sometimes within weeks but also after months or years(4, 18). A 
prospective cohort study undertaken by Massey(18, 19). and colleagues identified that self-reported 
nonadherence to immunosuppression medication increased significantly between 6 weeks and 6 
months post-transplant from 17% to 27% and that by 18 months, the rate of nonadherence had 
reached 31%. They assessed patient’s perceptions of the importance of medication adherence over 
time and while it was initially high, it decreased significantly over time.   
 
In a meta-analysis of adherence rates among solid organ transplant recipients, nonadherence to 
immunosuppression medication was shown to be the highest in the kidney transplant recipients at 
35.6 cases per 100 persons per year (PPY) compared to 14.5 cases per 100 PPY for heart recipients 
and 6.7 cases per 100PPY for liver recipients(20). This higher rate of nonadherence in the kidney 
transplant recipients is possibly because the consequences of nonadherence are higher in other 
SOTs.  Adherence with therapy is one of the criteria when listing a patient for transplant and it is 
possible that recipients of SOTs other than the kidney may be subject to more stringent psychosocial 
selection criteria.  
 
There are many reasons why patients do not adhere to their medication and their barriers to 
adherence can change over time. Patients who are nonadherent to immunosuppressant medication 
will often be nonadherent to other medicines prescribed for them, clinic attendance, diet, exercise, 
alcohol consumption, smoking and illicit drug use(1, 16). All of these factors will contribute to the 
overall morbidity and mortality of the patient. 
 
1.2 
RATIONALE FOR CURRENT STUDY 
Nonadherence to immunosuppressive medication post kidney transplant is a potent risk factor for 
rejection and graft loss. Clinicians often have little time to discuss medication adherence in detail 
with patients in the outpatient clinic and while pharmacists would be well placed to take on this role, 
they are under-utilised and under-resourced in transplant outpatient clinics. The aim of this study 

Immunosuppressant medication nonadherence intervention study 
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IRAS Project ID 232623 
will be to determine prospectively, using a multidimensional design, whether immunosuppression 
medication adherence can be improved in a group of patients receiving tailored medication 
adherence support form a pharmacist resulting in a reduction in the observed intrapatient variability 
(IPV) of tacrolimus trough levels and an improved attendance at outpatient clinic appointments. 
Adherence support will be provided for one year and will be individualised to each patient in the 
intervention group after identifying both their practical and perceptual barriers to adherence. A 
range of clinical outcomes will be assessed for all patients on a regular basis in order to determine 
whether the provision of effective medication adherence support for our kidney transplant patients 
may help to optimise the long-term outcomes of these transplants. 
 
2.  STUDY OBJECTIVES 
 
To improve immunosuppression medication adherence with pharmacist led, patient tailored 
adherence support  
 
To improve IPV of tacrolimus levels with pharmacist led, patient tailored adherence support 
 
To improve attendance at outpatient clinic appointments with pharmacist led, patient tailored 
adherence support 
 
To determine if there is a correlation between IPV of immunosuppression levels and the self-
reported and objectively measured adherence of the patient 
 
3.  STUDY DESIGN 
 
A prospective, multidimensional cohort study to include 42 kidney transplant patients with a high 
IPV of their tacrolimus levels from Imperial College Renal and Transplant Centre Outpatient Clinic. 
Patients recruited into the study will receive pharmacist led, patient tailored interventions to 
improve immunosuppressant medication adherence. Patients will be included in the study for one 
year from recruitment. 
 
Intervention:  
 
Patients will receive regular, intensive, personalised support from a pharmacist to improve 
adherence to immunosuppressive medications. The pharmacist will meet with the patient on a 
regular basis in the transplant outpatient clinic to identify their perceptual and practical barriers to 
adherence and agree a support plan that is tailored to them. 
 
Within the first two weeks of recruitment, the study pharmacist will meet with the patient in the 
transplant outpatient clinic to: 
 
• 
Undertake a full medication history 
• 
Discuss self-reported medication nonadherence  
• 
Undertake the BAASIS questionnaire  
 
Ask the patient to complete a Beliefs about Medicines Questionnaire (BMQ) 
 
Undertake a socioeconomic and educational assessment  
• 
Undertake to gain collateral reporting of nonadherence by clinicians, relatives, friends or 
carers  
• 
Perform a tacrolimus pill count  
• 
Check in-house dispensing records of tacrolimus 
• 
Identify barriers to adherence  

Immunosuppressant medication nonadherence intervention study 
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• 
Tailor interventions and support to the needs of the patient  
• 
Complete a motivational interview 
• 
Agree to meet again during an outpatient clinic visit within an agreed time which is 
appropriate for the patient needs and within 3 months 
 
This first visit will provide a baseline assessment of the patient’s medication adherence. 
 
Tailored interventions and support may include: 
 
• 
Setting alarms  
• 
Medication diary card or calendar 
• 
Medication compliance aid filled by the patient, family/carers or by a pharmacy professional 
• 
Adherence app  
• 
Reducing the complexity of the medication regime 
• 
Positioning medication within their daily routine eg. by toothbrush 
• 
Changing formulations  
• 
Additional education regarding need for medication / timing of doses 
• 
Referral to a social worker to assist with affordability of medicines 
• 
Referral to a psychologist to explore deeper psychological issues regarding medicines taking 
 
The structure of each follow up adherence review will be the same as the first formal adherence 
review with the exception that the BMQ will only be repeated at the end of the one year follow-up 
and the socioeconomic and educational assessment will only be undertaken at the first assessment 
review. Every patient will have a formal adherence assessment at 3, 6, 9 and 12 months. At the end 
of one year of follow-up, the specific benefits perceived by the patient of intensive adherence 
support from a pharmacist will be determined through a questionnaire.  
 
Baseline nonadherence will be measured at the first visit with the study pharmacist within two 
weeks of recruitment and then at 3, 6, 9 and 12 months. The IPV of their tacrolimus levels and their 
outpatient clinic nonattendance rate will be measured retrospectively in the 12 months prior to 
recruitment to the study and then prospectively at the end of the intervention year.  
 
 
3.1 
STUDY OUTCOME MEASURES 
 
Primary outcome measures 
 
1. 
Difference in adherence to immunosuppression medication measured by: 
 
 
Self-reporting of nonadherence by the patient 
 
BAASIS questionnaires 
 
Collateral reporting of nonadherence by clinicians, relatives, friends or carers  
 
Tacrolimus pill counts  
 
In-house dispensing records of tacrolimus 
 
Nonadherence will be scored using the Imperial College Renal and Transplant Centre classification of 
immunosuppressant medication nonadherence tool. 
 
2. 
Difference in the median IPV before and after the intervention year 
 
3. 
Difference in outpatient clinic nonattendance rate before and after the intervention year 

Immunosuppressant medication nonadherence intervention study 
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Secondary outcome measures 
 
Allograft outcome: 
• 
Biopsy proven ACR/AMR 
• 
Development of a DSA or transplant glomerulopathy 
 
Development of fibrosis, hyalinosis, calcineurin inhibitor (CNI) toxicity or diabetic change on 
biopsy 
• 
Graft loss 
• 
Death 
 
Allograft function: 
• 
Serum creatinine 
• 
eGFR 
• 
Proteinuria 
 
Haematocrit 
 
Albumin 
 
Haemoglobin 
• 
Tacrolimus levels 
 
Other: 
• 
Readmissions 
 
Standard blood tests will be performed at every clinic visit. 
 
4. 
PARTICIPANT ENTRY  
 
4.1 
PRE-REGISTRATION EVALUATIONS  
Adult kidney transplant patients with a functioning graft who have shown a pattern of nonadherent 
behaviour for at least six to twelve months prior to recruitment. Nonadherence will be 
demonstrated by a high IPV of their tacrolimus levels  
 
4.2 
INCLUSION CRITERIA  
Adult kidney transplant patients (18 years of age and above) 
Kidney transplant patients with an IPV of tacrolimus levels of greater than 18.15% in the previous 12 
months 
 
 
4.3 
EXCLUSION CRITERIA  
Antibody incompatible transplants including patients with preformed HLA and blood group 
incompatible 
Previous rejection 
Donor specific antibody positive 
HIV positive patients 
Simultaneous pancreas and kidney patients 
Paediatric patients (less than 18 years of age) 
 
 
 
 

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4.4 
INCLUDE IN IPV ANALYSIS 
 
Outpatient tacrolimus levels measured retrospectively in the 12 months prior to recruitment 
Outpatient tacrolimus levels measured prospectively 12 months after recruitment 
Patients who develop a DSA or rejection during the study will only have their tacrolimus levels prior 
to the event included in the analysis 
Patients who switch to Advagraf® during the study will only have their tacrolimus levels prior to the 
switch included in the analysis 
 
4.5 
EXCLUDE FROM IPV ANALYSIS 
 
All inpatient tacrolimus levels 
Tacrolimus levels during the period of instability caused by a significantly interacting co-prescribed 
medication 
 
4.6 
WITHDRAWAL CRITERIA 
Death 
Graft loss 
Transfer out of unit 
Loss of capacity 
 
Identifiable data already collected with consent would be retained and used in the study. No further 
data would be collected or any other research procedures carried out on or in relation to the 
participant 
 
5. 
ADVERSE EVENTS 
 
5.1 
DEFINITIONS   
 
Adverse Event (AE): any untoward medical occurrence in a patient or clinical study subject.   
 
Serious Adverse Event (SAE): any untoward and unexpected medical occurrence or effect that: 
 
Results in death 
 
Is life-threatening – refers to an event in which the subject was at risk of death at the 
time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe 
 
 
Requires hospitalisation, or prolongation of existing inpatients’ hospitalisation 
 
Results in persistent or significant disability or incapacity 
 
Is a congenital anomaly or birth defect 
 
Medical judgement should be exercised in deciding whether an AE is serious in other situations.  
Important AEs that are not immediately life-threatening or do not result in death or hospitalisation 
but may jeopardise the subject or may require intervention to prevent one of the other outcomes 
listed in the definition above, should also be considered serious. 
 
5.3 
REPORTING PROCEDURES 
All adverse events should be reported.  Depending on the nature of the event the reporting 
procedures below should be followed.  Any questions concerning adverse event reporting should be 
directed to the Chief Investigator in the first instance.   
 

Immunosuppressant medication nonadherence intervention study 
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5.3.1 Non serious AEs 
All such events, whether expected or not, should be recorded.   
 
5.3.2 Serious AEs 
An SAE form should be completed and faxed to the Chief Investigator within 24 hours.  However, 
relapse and death due to kidney transplantation and hospitalisations for elective treatment of a pre-
existing condition do not need reporting as SAEs. 
 
All SAEs should be reported to the Riverside Research Ethics Committee where in the opinion of the 
Chief Investigator, the event was: 
 
‘related’, ie resulted from the administration of any of the research procedures; and 
 
‘unexpected’, ie an event that is not listed in the protocol as an expected occurrence 
 
Reports of related and unexpected SAEs should be submitted within 15 days of the Chief Investigator 
becoming aware of the event, using the NRES SAE form for non-IMP studies.  The Chief Investigator 
must also notify the Sponsor of all SAEs. 
 
Local investigators should report any SAEs as required by their Local Research Ethics Committee, 
Sponsor and/or Research & Development Office. 
 
Contact details for reporting SAEs 
Fax 0208 383 8543, attention Dawn Goodall 
Please send SAE forms to: Dawn Goodall 
Tel: 0208 383 4247 (Mon to Fri 09.00 – 17.00) 
 
6. 
ASSESSMENT AND FOLLOW-UP  
 
All patients will be followed up in the transplant outpatient clinic at regular intervals as per current 
practice. Those enrolled in the study will be followed for 12 months and will have additional 
medication adherence assessments with the study pharmacist as outlined in section 3 (study 
design). 
 
The study will end following one year of adherence intervention and assessment for all patients 
enrolled in the study. 
 
 
7. 
STATISTICS AND DATA ANALYSIS 
 
The trial is powered (Type I error (α) 0.05 type II error (β) 0.10) to show a difference in IPV before 
and after the intervention of 35%. This predicted difference is based on clinical experience and 
judgment. An overall sample size of 42 patients will be recruited. An unlikely 20% losses (33 patients 
recruited and retained in the study) would result in an 80% power of demonstrating the same 
difference (Type I error (α) 0.05 type II error (β) 0.20).  
 
Standard and transplant specific demographics will be collected for all patients. Outcome data will 
be collected through interrogation of the hospital information system. Statistical analyses will be 
carried out using Medcalc or SPSS. Data will be summarised as mean (SD) for continuous variables 
and number of subjects (percent) for categorical variables. Chi-square and t-tests will be performed 

Immunosuppressant medication nonadherence intervention study 
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to determine significant differences in immunosuppressant medication adherence, IPV and clinic 
attendance before and after the intervention year. 
 
Data and all appropriate documentation will be stored for a minimum of 5 years after the 
completion of the study, including the follow-up period.   
 
 
8. 
REGULATORY ISSUES 
 
8.1 
ETHICS APPROVAL 
The Chief Investigator has obtained approval from the Riverside Research Ethics Committee and the 
HRA. The Chief Investigator will require a copy of the Trust Capacity and Capability approval email  
before accepting participants into the study.  The study will be conducted in accordance with the 
recommendations for physicians involved in research on human subjects adopted by the 18th World 
Medical Assembly, Helsinki 1964 and later revisions. 
 
8.2 
CONSENT  
Consent to enter the study must be sought from each participant only after a full explanation has 
been given, an information leaflet offered and time allowed for consideration.  Signed participant 
consent should be obtained.  The right of the participant to refuse to participate without giving 
reasons must be respected.  After the participant has entered the study the clinician remains free to 
give alternative treatment to that specified in the protocol at any stage if he/she feels it is in the 
participant’s best interest, but the reasons for doing so should be recorded.  In these cases the 
participants remain within the study for the purposes of follow-up and data analysis.  All participants 
are free to withdraw at any time from the protocol treatment without giving reasons and without 
prejudicing further treatment. Formal written consent will be obtained by a member of the research 
team at the time of recruitment in the Renal and Transplant Clinic at Hammersmith Hospital. 
 
8.3 
CONFIDENTIALITY 
The Chief Investigator will preserve the confidentiality of participants taking part in the study and is 
registered under the Data Protection Act. The Chief Investigator and other members of the research 
team are members of the healthcare team caring for the participants therefore have access to their 
personal information. Confidential patient information will be stored only on the Trust computer 
systems, all of which are password protected and will not be shared with anyone outside of the 
research or healthcare team. Non-anonymised data will be available to study clinicians only. 
Electronic data will be pseudonymised prior to analysis (ie each patient = unique number)and stored 
on the secure hospital systems all of which are password protected. Signed consent forms will be 
scanned onto the patient’s electronic record then destroyed. Non−anonymised data will be available 
only to members of the research team and will be stored only on the Trust computer systems, all of 
which are password protected and will not be shared with anyone outside of the research or 
healthcare team.  
 
8.4 
INDEMNITY 
Imperial College London holds negligent harm and non-negligent harm insurance policies which 
apply to this study. Imperial College Healthcare NHS Trust holds standard NHS Hospital Indemnity 
and insurance cover with NHS Litigation Authority for NHS Trusts in England, which apply to this 
study (delete as applicable) 
 
8.5 
SPONSOR 
Imperial College Healthcare NHS Trust will act as the main Sponsor for this study.  Delegated 
responsibilities will be assigned to the NHS trusts taking part in this study.   
 

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8.6 
FUNDING 
Imperial Health Charity fund  7089 are funding this study.   
 
8.7 
AUDITS  
The study may be subject to inspection and audit by Imperial College London under their remit as 
sponsor and other regulatory bodies to ensure adherence to GCP and the NHS Research Governance 
Framework for Health and Social Care (2nd edition).  
 
9. 
STUDY MANAGEMENT 
 
The day-to-day management of the study will be co-ordinated through a study specific steering 
group and the Imperial College Renal and Transplant Centre Research Group.   
 
10. 
PUBLICATION POLICY 
 
The outcomes of this study will be published in a high impact peer reviewed journal 
 
11. 
SUMMARY OF INVESTIGATIONS, TREATMENT AND ASSESSMENTS 
 
 
Exam 
Month of Treatment – clinic appointments will vary. This is an example only 
Pre-recruitment 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Clinic attendance 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
IPV tacrolimus levels 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Medication 
adherence review 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
12. 
APPENDICES 
 
Appendices should be additional information to the protocol and can consist of: 
 
 
Participant Information Sheet 
 
Consent form  
 
GP letter  
 
Questionnaire to measure the specific benefits perceived by the patient of intensive 
adherence support from a pharmacist 
 
Classification of immunosuppressant medication nonadherence tool 
 
BAASIS questionnaire 
 
 
 
 
 
 

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REFERENCES 
 
 
1. 
Kidney Disease: Improving Global Outcomes Transplant Work G. KDIGO clinical 
practice guideline for the care of kidney transplant recipients. American journal of 
transplantation : official journal of the American Society of Transplantation and the American 
Society of Transplant Surgeons. 2009;9 Suppl 3:S1-155. 
2. 
De Bleser L, Matteson M, Dobbels F, Russell C, De Geest S. Interventions to 
improve medication-adherence after transplantation: a systematic review. Transplant 
international : official journal of the European Society for Organ Transplantation. 
2009;22(8):780-97. 
3. 
Denhaerynck K, Steiger J, Bock A, Schafer-Keller P, Kofer S, Thannberger N, et al. 
Prevalence and risk factors of non-adherence with immunosuppressive medication in kidney 
transplant patients. American journal of transplantation : official journal of the American 
Society of Transplantation and the American Society of Transplant Surgeons. 2007;7(1):108-
16. 
4. 
Fine RN, Becker Y, De Geest S, Eisen H, Ettenger R, Evans R, et al. Nonadherence 
consensus conference summary report. American journal of transplantation : official journal 
of the American Society of Transplantation and the American Society of Transplant 
Surgeons. 2009;9(1):35-41. 
5. 
Gaston RS, Hudson SL, Ward M, Jones P, Macon R. Late renal allograft loss: 
noncompliance masquerading as chronic rejection. Transplantation proceedings. 
1999;31(4A):21S-3S. 
6. 
Morrissey PE, Flynn ML, Lin S. Medication noncompliance and its implications in 
transplant recipients. Drugs. 2007;67(10):1463-81. 
7. 
Morrissey PE, Reinert S, Yango A, Gautam A, Monaco A, Gohh R. Factors 
contributing to acute rejection in renal transplantation: the role of noncompliance. 
Transplantation proceedings. 2005;37(5):2044-7. 
8. 
Prendergast MB, Gaston RS. Optimizing medication adherence: an ongoing 
opportunity to improve outcomes after kidney transplantation. Clinical journal of the 
American Society of Nephrology : CJASN. 2010;5(7):1305-11. 
9. 
Schafer-Keller P, Steiger J, Bock A, Denhaerynck K, De Geest S. Diagnostic 
accuracy of measurement methods to assess non-adherence to immunosuppressive drugs 
in kidney transplant recipients. American journal of transplantation : official journal of the 
American Society of Transplantation and the American Society of Transplant Surgeons. 
2008;8(3):616-26. 
10. 
Wiebe C, Nevins TE, Robiner WN, Thomas W, Matas AJ, Nickerson PW. The 
Synergistic Effect of Class II HLA Epitope-Mismatch and Nonadherence on Acute Rejection 
and Graft Survival. American journal of transplantation : official journal of the American 
Society of Transplantation and the American Society of Transplant Surgeons. 
2015;15(8):2197-202. 
11. 
Sellares J, de Freitas DG, Mengel M, Reeve J, Einecke G, Sis B, et al. 
Understanding the causes of kidney transplant failure: the dominant role of antibody-
mediated rejection and nonadherence. American journal of transplantation : official journal of 
the American Society of Transplantation and the American Society of Transplant Surgeons. 
2012;12(2):388-99. 
12. 
Roberts DM, Jiang SH, Chadban SJ. The treatment of acute antibody-mediated 
rejection in kidney transplant recipients-a systematic review. Transplantation. 
2012;94(8):775-83. 
13. 
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