Single Center, Pilot Evaluation of Home-based Therapeutic Drug Monitoring for Tacrolimus and Mycophenolate in Kidney Transplantation
Phase: NA
Conditions: Kidney Transplant
Sponsor: University of Michigan

PROTOCOL HUM NUMBER: HUM00198148 
NCT number: NCT05005221  
 
PROTOCOL TITLE 
Single center, pilot evaluation of home-based therapeutic drug monitoring for tacrolimus and 
mycophenolate in kidney transplantation 
 
SHORT TITLE 
Home-based Therapeutic Drug Monitoring in Kidney Transplantation 
 
 
 
 
Initial version: 
 
 4/16/2021 
Amended: 
 
 
 1/7/2022 
 
 
 
 
 8/4/2022 
 
 
 
 
 3/7/2023 
 
NOTE: To effectively manage restrictions put in place during public health or civil emergency 
or restrictions (i.e. COVID-19 pandemic) changes to protocol-required items are to be made to 
minimize or eliminate immediate hazards or to protect the life and well-being of research 
participants (e.g., to limit exposure to infectious pathogens). These changes are listed in 
Appendix A of the protocol (Contingency Operation Plan). 

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TABLE OF CONTENT 
 
ABBREVIATIONS ........................................................................................................................ 0 
STUDY SYNOPSIS ....................................................................................................................... 1 
STUDY SCHEMA.......................................................................................................................... 4 
1.0 
BACKGROUND AND RATIONALE ................................................................................ 6 
1.1 
Background ...................................................................................................................... 6 
1.2 
Rationale........................................................................................................................... 6 
2.0 
STUDY DESIGN, OBJECTIVES AND OUTCOME MEASURES .................................. 8 
2.1 
Primary Objective (Part 2) ............................................................................................... 8 
2.2 
Secondary Objectives (Part 1) .......................................................................................... 8 
2.3 
Exploratory Objectives ..................................................................................................... 8 
3.0 
SUBJECT ELIGIBILITY .................................................................................................... 9 
3.1 
Inclusion Criteria .............................................................................................................. 9 
3.2 
Exclusion Criteria ............................................................................................................. 9 
3.3 
Inclusion Criteria .............................................................................................................. 9 
3.4 
Exclusion Criteria ............................................................................................................. 9 
4.0 
SUBJECT SCREENING, ENROLMENT, AND RECRUITMENT ................................ 10 
4.1 
Subject Recruitment and Retention ................................................................................ 10 
4.2 
Screen Failures ............................................................................................................... 10 
4.3 
Randomization ............................................................................................................... 11 
4.4 
Blinding .......................................................................................................................... 11 
5.0 
INTERVENTION PLAN (PART 2 ONLY)...................................................................... 11 
5.1 
Intervention Administration ........................................................................................... 11 
5.2 
Immunosuppression Dosage and Administration .......................................................... 12 
5.3 
Concomitant Medications/Treatments ........................................................................... 12 

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5.4 
Duration of Study Involvement ...................................................................................... 12 
5.5 
Off Intervention Criteria................................................................................................. 13 
5.6 
Duration of Follow-Up ................................................................................................... 13 
5.7 
Off Study Criteria ........................................................................................................... 13 
5.8 
Subject Replacement ...................................................................................................... 14 
6.0 
STUDY PROCEDURES AND EFFICACY ASSESSMENT ........................................... 14 
6.1 
Study Procedures and Assessments................................................................................ 14 
6.2 
Safety/Tolerability .......................................................................................................... 16 
6.3 
Time and Events Table ................................................................................................... 16 
7.0 
ADVERSE EVENTS ......................................................................................................... 17 
7.1 
Adverse Event Reporting Requirements ........................................................................ 17 
7.2 
Reporting of Unanticipated Problems ............................................................................ 18 
7.3 
Reporting of Pregnancy .................................................................................................. 19 
8.0 
DEVICE INFORMATION ................................................................................................ 19 
9.0 
STATISTICAL CONSIDERATIONS............................................................................... 20 
9.1 
Study Design/Study Outcome Measures ........................................................................ 20 
9.2 
Primary Objective (Part 2) ............................................................................................. 20 
9.3 
Secondary Objectives (Part 1) ........................................................................................ 21 
9.4 
Exploratory Objectives ................................................................................................... 21 
9.5 
Sample Size and Accrual................................................................................................ 21 
9.6 
Data Analyses Plan......................................................................................................... 22 
10. 
DATA AND SAFETY MONITORING ............................................................................ 24 
11. 
QUALITY ASSURANCE AND AUDITS ........................................................................ 24 
a. 
Audits and Inspections ................................................................................................... 24 
b. 
Protocol Deviations ........................................................................................................ 24 

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12. 
REGULATORY ................................................................................................................ 25 
a. 
Institutional Review Board (IRB) .................................................................................. 25 
b. 
Subject Information and Consent ................................................................................... 25 
13. 
REFERENCES .................................................................................................................. 26 
14. 
APPENDICES ................................................................................................................... 30 

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ABBREVIATIONS 
 
AE 
Adverse Event 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
DBS 
Dried blood spot 
IRB 
Institutional Review Board 
LC-MS/MS 
Liquid Chromatography with tandem mass spectrometry 
MOP 
Manual of Procedures 
PI 
Principal Investigator 
PO 
per os/by mouth/orally 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
TDM 
Therapeutic drug monitoring  
 
 

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STUDY SYNOPSIS 
Title 
Single center, pilot evaluation of home-based 
therapeutic drug monitoring for tacrolimus and 
mycophenolate in kidney transplantation 
Study Description  
Part 1: Clinical validation of bioanalytical assay 
Part 2: Prospective, randomized, pilot evaluation of a 
text messaging intervention to facilitate self-collection 
of dried blood samples for tacrolimus and 
mycophenolate therapeutic drug monitoring 
Study Duration 
Part 1: 3 days 
Part 2: Enrollment duration: 3 months (up to 4 months 
if participating in qualitative interview) 
Subject follow-up duration: 0 months 
Overall study duration: 24 months  
Study Center(s) 
Single-center 
University of Michigan  
Objectives 
Evaluate tools to facilitate patient self-collection of 
samples for therapeutic drug monitoring of tacrolimus 
and mycophenolate including the self-collection 
device (Tasso-M20) and text messaging reminders.  
Number of Subjects 
Part 1: 45 (up to 90 if participants do not provide 2 
sample, need to obtain 90 paired samples (Tasso vs. 
venipuncture) for approprirate statistical power) 
Part 2: 45 
Disease/condition  
Part 1: Solid organ transplant recipients requiring 
immunosuppression with tacrolimus and 
mycophenolate 
Part 2: Kidney transplantation requiring 
immunosuppression with tacrolimus and 
mycophenolate 
Inclusion/Exclusion Criteria 
See Section 3.0 for a complete list of inclusion and 
exclusion criteria 
Description of Study 
Intervention: 
Part 1: No intervention. Subjects will collect capillary 
samples using the Tasso-M20 and Mitra dried 
microsampling devices concurrently with their 
clinically indicated venipucture. 
Part 2: All subjects will obtain self-collected dried 
blood spots for analysis of tacrolimus and 
mycophenolate using the Tasso-M20 device 
(Illustrated below). On two separate days 
approximately 6 weeks apart. Subjects will be 
randomized to two text messaging interventions to 
provide reminders and guide collection of samples in 
the home environment.  
 

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No changes will be made to the subjects’ treatment 
based on data collected in this study. All changes to 
the medication regimen will be made at the treating 
provider’s discretion.  
Duration of Intervention 
Part 1: no intervention (sample collection duration up 
to 2 days) 
Part 2: 3 months 
Statistical Methodology 
Part 1: Bioanalytical method agreement will be 
assessed by Passing-Bablok regression and Bland-
Altman plots. 
Part 2: The primary outcome is successful to home 
collection of samples. Multivariable logistic 
regression will be used to identify participant 
characteristics associated with successful home 
collection.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Illustration of the Tasso-M20 dried blood samples collection kit (A) that includes self-
placement on the upper arm (B) followed by activation (clicking the red button), timed 
collection (C), and automatic sealed storage of four samples in a cartridge (D) for 
bioanalysis 
 
 
 
 
Illustration of the Mitra dired blood sample collection kit (A) that requires sampling from 
the capillary via fingerstick with the sample time for bioanalysis (B) 
 
 
 

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STUDY SCHEMA 
Part 1:  
 
Prior to 
Enrollment 
Study Day -14 
(± 14 days) 
Total n=up to 90 (minimum of 50 samples):  Obtain informed consent.  
Collect paired dried blood (Tasso-M20 and Mitra) and venipuncture 
samples for tacrolimus and mycophenolate trough concentrations. 
Collect patient reported experience questionnaire 
If patient remains hospitalized with a second 2nd standard of care 
tacrolimus trough ordered: Collect paired dried blood and venipuncture 
samples for tacrolimus and mycophenolate trough concentrations. 
Collect patient reported experience questionnaire (2nd day 
questionnaire may be obtained even if the patient does not have a 
second set of samples obtained) 
Visit 1 
Study Day 1  
Visit 2 
Study Day 2 
(±7 days)  

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Part 2:  
 
Bidirectional text 
communication (N=30) 
Prior to 
Enrollment 
Study Day -14 
(± 14 days) 
Goal n=45:  Obtain informed consent. Provide education on sample self-
collection using Tasso-M20 device & text messaging. Collect baseline 
questionnaire data including medication adherence. Review medication list.  
Administer text message intervention (beginning 48 hrs prior and 
ending 48 hours after). 
Patient collected dried blood samples at time 0, 1hr, 4hr, and 8hr 
Document collection times, medication doses in patient diary 
Mail samples to study site  
Randomize 
Unidirectional text 
reminders (N=15) 
Semi-structured qualitative 
interview 
Self-collection 1 
Study Day 14 
(±14 days) 
Self-collection 2 
Study Day 56 
(±14 days)  
Visit 3  
(if applicable) 
Study Day 60 
(±28 days)   
Administer text message intervention (beginning 48 hrs prior and 
ending 48 hours after). 
Patient collected dried blood samples at time 0, 1hr, 4hr, and 8hr 
Document collection times, medication doses in patient diary  
Mail samples to study site 
Purposive sampling (min N= 10) 

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1.0 BACKGROUND AND RATIONALE 
1.1 Background 
Optimal immunosuppression therapy is critical for kidney transplantation success. The care 
of transplant recipients has improved remarkably over the last 50 years, and transplantation 
offers a clear survival benefit, higher quality of life, and lower cost than dialysis.1-4 Yet, 
10-year all-cause graft failure remains high at approximately 50%. This number 
corresponds to many recipients requiring a second or third transplant, whereas, for others, 
it represents premature death from cardiovascular disease, infection, and malignancy.2, 5 
Importantly, the cause of negative transplant outcomes can often be traced in some capacity 
to immunosuppression, and optimization of the drug regimen has the potential to improve 
long-term graft and patient survival.6-8 New therapeutic options have failed to emerge, and 
the standard of care immunosuppression of tacrolimus and mycophenolate has not changed 
in nearly 20 years. Current practice is limited in its ability to balance the prevention of 
immune-mediated graft damage with the development of adverse side effects. Dose 
modifications remain reactive and primarily based on clinical evaluation and trough 
concentrations of tacrolimus, which does not adequately allow preemptive identification 
of patients at risk. As a result, precision pharmacotherapy, enhanced pharmacokinetic (PK) 
monitoring, and assessment of the alloimmune response are considered research priorities 
by both transplant professionals and patients.9, 10 
These observations have led to the pursuit of expanded therapeutic drug monitoring (TDM) 
encompassing pharmacokinetic monitoring of drug exposure by estimating area under the 
concentration-time curve (AUC) for both tacrolimus and mycophenolate and evaluation of 
potential immune biomarkers. In several studies, estimating AUC has better correlated with 
reductions in acute rejection.11-15  Similarly, valganciclovir/ganciclovir, a commonly 
received antiviral, displays larger inter- and intra-patient PK variability. A reported 50 to 
80% of patients do not achieve therapeutic exposure with current dosing 
recommendations.16 This is particularly relevant in kidney transplantation where low and 
fluctuating GFR is common in the post-operative period; subtherapeutic exposure is most 
common when adjusting the dose based on the current manufacturer recommendations for 
altered kidney function. Unfortunately, AUC is also the PK parameter associated with 
ganciclovir efficacy and toxicity.17 Additionally, relationships with several immune 
biomarkers (e.g., donor-derived cell-free DNA, NFAT-regulated gene expression) and 
outcomes have also been identified with evidence supporting use as pharmacodynamic 
markers.18 Monitoring concentrations of metabolites, such as mycophenolic acid 
glucuronide, may also be beneficial as they offer insight into metabolic capacity and are 
hypothesized to be associated with toxicity but are incompletely studied.19 Further 
knowledge of the impact of enhanced TDM remains needed to confirm optimal AUC 
targets and establish the best biomarker strategy to classify subclinical immune activity in 
large, prospective, longitudinal clinical trials. Finally, widescale implementation in 
practice is hampered by the perceived complexity compared to trough concentration 
monitoring. The full realization of the therapeutic potential will remain difficult in the 
absence of new tools to increase the translatability by reducing cost and patient burden.  
1.2 Rationale 

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Forward progress in precision dosing using AUC and biomarker monitoring is hindered by 
the logistics of adequately powered, prospective studies. Home-based therapeutic drug 
monitoring (TDM) using volumetric dried blood microsampling to collect multiple 
concentration-time points for Bayesian AUC estimation and immune biomarker analysis is 
an innovative, practical, and cost-effective approach that could be used to implement 
precision dosing for both future studies and clinical practice.20-22  
Collection of dried capillary blood is a minimally invasive method for in-home use where 
patients self-collect small blood samples. Dried blood samples have been used for nearly a 
decade to obtain specimens for immunosuppression concentrations but can be limited by 
extraction recovery, hematocrit effect, and sample quality.23-28 Volumetric, whole sample 
analysis has the potential to mitigate these problems. Volumetric 
sampling has been used successfully to obtain immunosuppression and 
ganciclovir concentrations in several small studies.20, 29-32  The next 
generation collection device, Tasso-M20 (Tasso Inc, Seattle WA), offers 
precise volumetric sampling with the potential to improve patient 
satisfaction and acceptability by offering a near painless experience but 
has not yet been used in transplantation. The device includes a self-
contained lancet that obtains four 20 µL dried capillary samples from the 
upper arm during a single, button-activated collection event (Figure 1). 
In transplantation, existing literature suggests patients can collect dried 
blood samples at home, are generally satisfied with the procedure, and 
are willing to provide more samples with this method, particularly if it 
can replace venipuncture or reduce clinic visits.22, 24, 27, 31, 33 However, 
data are primarily limited to non-US populations and lack a robust framework to ensure a 
complete understanding of the behavior. Further, preliminary data shows that adherence to 
the collection is low, with 42-55% completion rates without intervention.22, 27 Additional 
work is needed to develop strategies to increase adherence to monitoring. Text messaging 
reminders have been demonstrated to improve medication adherence and other positive 
health behaviors.34 Text messages are low cost with minimal infrastructure requirements 
and more accessible to patients with a low technology literacy or in rural areas with low 
cellular bandwidth. In a 2015 survey of kidney transplant recipients, 96% owned a mobile 
phone and 74% used text messaging compared to 47% who used apps.35 Text messaging 
is the preferred method of health communication in adolescent and young adult 
recipients.36 The use of text messaging offers the potential to be a viable tool to increase 
adherence to home-based TDM for most of the transplant population. 
Our contributions are expected to develop a patient-centric strategy to allow frequent, 
longitudinal, minimally invasive sample collection for bioanalysis of immunosuppression 
and other supportive therapy drug concentrations. These contributions will be significant 
because they are expected to overcome many barriers that have limited progress towards 
enhanced precision pharmacotherapy in transplantation. The methods will facilitate 
decentralized multicenter clinical trials by reducing costs and simplifying biorepositories 
to achieve the sample sizes necessary to conclusively establish the benefits of expanded 
TDM on long-term patient outcomes. Further, improving the technical capacity of home-
based sampling to substitute for frequent phlebotomy will improve patients’ quality of life 
by allowing increased autonomy to self-monitor by collecting blood samples at home. 

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2.0 STUDY DESIGN, OBJECTIVES AND OUTCOME MEASURES 
This will be a single center, randomized, pilot evaluation of a text messaging intervention 
to facilitate self-collection of dried blood samples for tacrolimus,  mycophenolate, and 
val/ganciclovir therapeutic drug monitoring. Particpants are not required to be receiving 
val/ganciclovir for participation but the concentration will be analyzed if the drug is 
concommitently being received by the participant under the direction of the treated 
clinical team.  
2.1 Primary Objective (Part 2) 
2.1.1 To compare the effect of bidirectional text communication on adherence to 
and accuracy of home-based AUC collection versus unidirectional text 
reminders in kidney transplant recipients receiving tacrolimus and 
mycophenolate. 
 
Primary Outcome Measure: successful home-based TDM defined as the 
timely receipt of samples that are adequate for pharmacokinetic analysis.  
2.2 Secondary Objectives (Part 1) 
 
2.2.1 To assess the bioanalytical agreement of two sample collection methods (dried 
blood spot and venipuncture) as measured by Liquid Chromatography with 
tandem mass spectrometry (LC-MS/MS). 
 
Secondary Outcome Measure: difference between drug concentrations 
measured from concurrent dried blood spot and venipuncture samples.  
2.3 Exploratory Objectives  
 
2.3.1 To evaluate the predictive performance of a mycophenolate matrix conversion 
equation. (Part 1) 
 
Exploratory Outcome Measure: median percentage predictive error and 
median absolute predictive error 
 
2.3.2 To assess the bioanalytical agreement of two sample collection methods (dried 
blood spot and venipuncture) as measured by LC-MS/MS assay at the 
University of Michigan PK Core and Michigan Medicine Clinical laboratory. 
(Part 1) 
 
Exploratory Outcome Measure: difference between drug concentrations 
measured from the two LC-MS/MS assays. 
 
2.3.3 To evaluate participant characteristics based on the Theoretical Domains 
Framework associated with successful home-based TDM. (Part 2) 
 

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Exploratory Outcome Measure: The relationship between patient 
characteristics and successful home-based TDM 
 
2.3.4 To evaluate differences in participant reported experiences between the 
Tasso-M20 device and Mitra device (Part 1) 
 
Exploratory Outcome Measure: difference between patient reported 
experience scores associated with the two sample collection devices 
 
3.0 SUBJECT ELIGIBILITY 
Subjects must meet all of the selection criteria to be enrolled in the study. Study treatment 
may not begin until a subject has provided informed consent and meets the eligibility 
criteria. 
Part 1:  
3.1 Inclusion Criteria 
1. Recipient of a solid organ transplant 
2. Male or Female adult (≥ 18 years) 
3. Receiving tacrolimus and mycophenolate 
4. Ability to understand and willingness to sign a written informed consent 
3.2 Exclusion Criteria 
1. Hemoglobin <8 g/dL 
2. History of allergy to tape adhesives  
 
 
Part 2:  
3.3 Inclusion Criteria 
1. Recipient of a kidney or kidney/pancreas transplant  
2. Male or Female adult (≥ 18 years) 
3. Receiving immediate release tacrolimus and mycophenolate mofetil  
4. Participant is willing to receive text notifications and has a mobile device capable 
of receiving texts 
5. Ability to understand and willingness to sign a written informed consent. 
6. Ability to understand, read, and speak English. 
3.4 Exclusion Criteria 

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1. Recipient of a multi-organ transplant (other than pancreas). 
2. History of allergy to tape adhesives 
Subjects may participate in both part 1 and part 2. Subjects participating in part 1 
expressing interest in part 2 will approached again once stable in the outpatient setting. 
Partipiants will sign separate consent for each part of the study.  
4.0 SUBJECT SCREENING, ENROLMENT, AND RECRUITMENT 
A potential study subject who has been screened for the trial and who has signed the 
Informed Consent document will be initially documented on a Screening and Enrollment 
Log. 
 
It is the responsibility of the investigator to determine subject eligibility prior to enrollment. 
After subject eligibility has been determined, a signed statement (i.e. eligibility checklist) 
by the investigator attesting eligibility will be included in the subject file. In addition, 
source documentation supporting each eligibility criteria will be placed within the subject 
file. 
4.1 Subject Recruitment and Retention  
Part 1: Participants will be recruited from the inpatient transplant surgery service. 
Potentially eligible participants will be approached by the study team during admission to 
consider participation. For living donor transplant recipients, the study team may also 
approach potential participants during their History and Physical appointment typically 
scheduled 7-10 days before surgery.  
 
Part 2: Participants will be recruited from the outpatient kidney transplant clinic at 
Michigan Medicine. Potentially eligible participants will be sent a letter describing the 
study and inviting the patient to contact the study team and/or the study team will contact 
participants via telephone if not attending clinic visits in person. The letter will be sent to 
the home address in a sealed envelope. Patients may also be approached during clinic visits 
to discuss the study. An incentive payment of $20 will be provided for completion of each 
study visit or home collection (participants may receive a total of $60). Patients may also 
be contacted via telephone to enhance retention if expected samples are not received.  
 
Women and minorities will be recruited using the same strategy and are expected to be 
recruited at a rate consistent with their incidence in the transplant population at the 
University of Michigan. 
4.2 Screen Failures 
For part 1: Screen failures are defined as particpants who consent to participate in the 
clinical trail but do not subsequently have at least 1 set of paired samples obtained.  
For part 2: Screen failures are defined as participants who consent to participate in the 
clinical trial but are not subsequently randomly assigned to the study intervention or 
entered in the study. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants, to meet the Consolidated Standards of 

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Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
 
Individuals who do not meet the criteria for participation in this trial (screen failure) will 
not be rescreened. Screen failures will be replaced.  
4.3 Randomization 
Part 1: no randomization 
Part 2: 45 patients who meet the inclusion criteria will be randomized in a 1:2 allocation 
ratio to receive one of two text messaging interventions stratified by age ≥ or < 65 years. 
The randomization list will be generated by the study biostatistician.  
4.4 Blinding 
 
Part 2: As subjects will be aware of the frequency and type of text messages received, 
blinding of patients is not possible. As a result, baseline data will be collected prior to 
randomization. Additionally, purposive sampling for qualitative interviews requires the 
investigator to be unblinded to study group.  
5.0 INTERVENTION PLAN (PART 2 ONLY) 
5.1 Intervention Administration 
All participants will self-collect dried blood samples using the Tasso-M20 device at the 
specified intervals. Each self-collection will obtain up to 80µL of capillary blood (4 x 20µL 
samples). Dried blood samples will be obtained concurrently with venipuncture samples at 
study visit 1 and 2. The participants will self-collect dried blood samples in their home 
environment for AUC analysis on two occasions. Self-collected samples will be collected 
immediately prior to the morning dose of tacrolimus and mycophenolate (C0) and at 
approximately 1, 4, and 8 hours after the dose.  
 
To promote adherence and accurate sample collection, participants will be randomized to 
1 of 2 automated text messaging interventions. Messages will be sent using a commercial 
web to text messaging gateway (Twilio). Twilio will be enabled in the REDCap project. 
Message replies will be stored in REDCap not on Twilio servers. The request inspector 
will be disabled in Twilio as required by REDCAP for HIPPA compliance. No protected 
health information (PHI) or identifying information will be in messages (See Table 1 for 
message content). A control group without messages will not be used due to preexisting 
knowledge of low rates of completion without intervention.  
Anticipated sample collection dates and times will be discussed with the participant during 
the baseline visit to trigger messaging timeline.If a response is received to any message not 
using an expected keyword, the recipient will receive a text message that the entery is an 
invalid value and to try again. The partipciants will be educted to contact the study team 
with any issues.    
 

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The participant will be able to opt-out of messages with the standard keywords: “cancel”, 
“stop”, “end”, “quit”, “stopall”, and “unsubscribe.” In response they will receive the 
following message: “You have successfully been unsubscribed. You will not received any 
more messages from this number. Someone from the study team will contact you to follow 
up. Reply START to resubscribe.  
 
In response to the keywords “help” or “info” participants will receive the following 
message: “For help, please call the study team (734) 647-1281 or email 
aleino@umich.edu.” 
 
Upon completion of study visit 3 and all study blood sample collections, a subset of patients 
will be selected for semi-structured qualitative interviews to further explore the home-
based TDM process. The interview guide is provided in Appendix C and is informed by 
the Theoretical Domains Framework mapped to the Capability-Opportunity-Motivation 
and Behavior system. Patients will be selected using maximum variation purposive 
sampling to capture multiple perspectives, including those demonstrating extremes in 
adherence, self-efficacy, diabetes status, and time post-transplant. 
5.2 Immunosuppression Dosage and Administration 
Participants will continue their prescribed regimen of oral tacrolimus and mycophenolate. 
No changes will be made to the subject’s medication therapy as part of the study. The 
participant will continue their own supply of medication provided by their local pharmacy. 
Medication will not be supplied by the study. Dose adjustments may be made by the 
treating provider based on standard of care laboratory results or as determined by the 
treating provider to be clinically indicated. Dose adjustments will be documented in the 
study record. 
  
The investigator will promote compliance by instructing the subject to take the study drug 
exactly as prescribed and by stating that compliance is necessary for the subject’s safety 
and the validity of the study. The subject should be instructed to contact the investigator if 
he/she is unable for any reason to take the study drug as prescribed. If vomiting occurs 
within 2 hours after administration of the dose on a sample collection day, the patient may 
be asked to repeat the collection at a later date at the discretion of the investigator. 
Adherence to the immunosuppressive regimen will be monitored using patient self-report 
and patient diary review.  
5.3 Concomitant Medications/Treatments 
Concomitant medications will be administered per institution standard of care. 
Concomitant medication is defined as any prescription or over-the-counter preparation 
including vitamins and supplements.  Concomitant medications will be recorded at the time 
of consent and visit 2 during part 2 of the study.  
5.4 Duration of Study Involvement  
Part 1: Study participant may continue for up to 7 days or until one of the following criteria 
apply: 

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• Subject’s immunosuppressive regimen no longer includes tacrolimus and 
mycophenolate 
• Subject voluntarily withdraws 
• Study completes the study assessments (2 paired sample collections) 
• Subject is discharged 
• Subject hemoglobin falls below 8g/dL 
 
Part 2: The intervention may continue for 26 weeks or until one of the following criteria 
apply: 
• Subject’s immunosuppressive regimen no longer includes tacrolimus and 
mycophenolate.  
• Subject voluntarily withdraws from treatment  
• Subject transfers care from the Michigan Medicine  
• Subject completes the required study assessments OR 
• General or specific changes in the subject’s condition render the subject 
unacceptable for further treatment in the judgment of the investigator 
5.5 Off Intervention Criteria  
Subjects will be removed from the protocol intervention when any of the criteria listed in 
Section 5.4 apply. Document in the source the reason for ending the protocol and the date 
the subject was removed from the protocol. All subjects who discontinue treatment should 
comply with protocol specific follow-up procedures as outlined in Section 5.7. The only 
exception to this requirement is when a subject withdraws consent for all study procedures 
or loses the ability to consent freely. 
5.6 Duration of Follow-Up 
Due to the minimal risk and nature of the intervention participants will not be followed 
beyond the completion of study visits.  
5.7 Off Study Criteria 
Subjects may request to withdraw from the study at any time, or they may be withdrawn at 
the discretion of the investigator for safety, behavioral, or administrative reasons. Prior to 
study withdrawal, participants may be asked if they are willing to complete the end of study 
survey and be considered for participation in the qualitative interview regarding their 
experience.  
 
The reason(s) for discontinuation from study will be documented and may include: 
 
1. Subject withdraws consent (termination of treatment and follow-up); 
2. Loss of ability to freely provide consent through imprisonment or involuntary 
incarceration for treatment; 
3. Subject is unable to comply with protocol requirements; 
4. Treating physician judges that continuation on the study would not be in the 
subject’s best interest; 

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5. Lost to Follow-up. If a research subject cannot be located for 3 months, the subject 
may be considered “lost to follow-up.” All attempts to contact the subject during 
the three months must be documented; 
6. Termination of the study by The University of Michigan 
7. Subject completes protocol treatment and follow-up criteria. 
5.8 Subject Replacement 
Part 1: Enrolled subjects may be replaced if paired samples are not successfully obtained 
on at least one occasion.  
 
Part 2: Enrolled subjects may be replaced if they do not attempt at least one at-home blood 
collection.  
6.0 STUDY PROCEDURES AND EFFICACY ASSESSMENT 
6.1 Study Procedures and Assessments 
This section contains a list and description of the study evaluations. 
 
Part 1:  
o During study visits 1 and 2 the following specimens will be collected for 
study purposes: 
▪ One 6-mL red top tube 
• One will be sent to the Michigan Medicine clinical 
laboratory for determination of mycophenolic acid and 
mycophenolic acid glucuronide concentration from serum. 
The results will be reported in the electronic medical record 
and will be available to the patient's clinical care team. 
▪ Four 20-µL capillary dried blood samples via Tasso-M20 device for 
determination of tacrolimus, mycophenolic acid, mycophenolic acid 
glucuronide, and ganciclovir (if applicable) concentrations by the 
University of Michigan PK Core. These results will be considered 
investigational and will not be shared with the patient or care team.  
▪ Two 20-µL capillary dried blood samples via Mitra device for 
determination of tacrolimus, mycophenolic acid, mycophenolic acid 
glucuronide, and ganciclovir (if applicable) concentrations by the 
University of Michigan PK Core. These results will be considered 
investigational and will not be shared with the patient or care team.  
 
Standard of care labs will also be drawn at this time and processed by the Michigan 
Medicine clinical laboratory. Results for hemoglobin, hematocrit, albumin, and tacrolimus 
concentration will be collected from the electronic medication record for study purposes.  
 
Study staff will collect any remaining/leftover blood from the Michigan Medicine clinical 
laboratory for additional analysis in the University of Michigan PK Core.  
Participants will also complete self-report questionnaires describing and comparing the 
sample collection methods (Appendix B) 

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Part 2: 
• Demographics including height and weight: will be recorded as reported by the 
patient or documented in the electronic medical record during the screening visit.  
• Education on Tasso device utilization and diary documentation will occur after 
consent has been obtained at the baseline visit (may be the same day as consent). 
Education will be provided in a private space (such as clinic room) if completed in 
person. Education may also be conducted virtually at time where the patient can 
secure privacy. 
• Biological specimen collection and laboratory evaluations: 
 
o During home-collection 1 and 2 the following specimens will be collected 
for study purposes:  
▪ Four 20-µL capillary dried blood samples via Tasso-M20 device 
will be obtained at 4 time points (0, 1, 4, and 8hrs after morning 
tacrolimus/mycophenolate administration). A total of 320 µL will 
be collected during each home-collection These samples will be 
used for determination of tacrolimus, mycophenolic acid, 
mycophenolic acid glucuronide concentrations by the University of 
Michigan PK Core. These results will be considered investigational 
and will not be shared with the patient or care team.  
▪ The Tasso-M20 device will be provided to the patient prior to each 
sample collection via US mail. The patient will also be provided 
with a pre-paid mailer to return the samples to the study site.  
▪ Each collection day will require four Tasso devices (one for each 
time point). The devices will be numbered to facilitate patient use.  
 
The results of any study-specific laboratory evaluations completed by the PK core will not 
be used to adjust medication therapy or be provided to the participant. The mycophenolate 
trough concentrations in addition to the standard of care labs processed by the Michigan 
Medicine Clinical lab will be available in the electronic health record for review by the 
participant.  
 
• Administration of study instruments for subject-reported outcomes (Appendix C): 
o During the Baseline visit participants will complete questionnaire packet 1 
which includes: 
▪ PROMIS Self-efficacy: Managing Medications/Treatments (8 
items)37 
▪ Medical Outcomes Social Support Scale (19 items)38 
▪ Transplant Effects Questionnaire (worry, guilt, disclosure, and 
responsibility) (18 items)39 
▪ Kidney Transplant Understanding Tool (abbreviated to the 20 items 
related to medication therapy and monitoring)40 
o During the home collections 1 and 2 participants will complete the study 
diary which includes: 
▪ Medication dose times for the 48 hr prior to collection 

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▪ Sample collection times 
o During the home collections 1 and 2 participants will complete ecological 
momentary assessments via text message 
▪ Pain intensity 
▪ Interruption in daily routine 
▪ Difficulty of sample collection 
▪ 48 hours after sample collection safety will be assessed via text 
message 
o At end of study participants will complete questionnaire packet 2 which 
includes:  
▪ Self-reported adherence assessment 
▪ Acceptability and Feasibility of Implementation Measure (8 items)41 
o During visit 3 selected participants will participate in a semi-structured 
qualitative interview. The interview guide is provided in Appendix D. 
6.2 Safety/Tolerability 
Patients will complete ecological momentary assessments to document the participants 
experience by rating pain intensity, interruption in daily routine, and difficulty on a scale 
of 0 to 10 at the time of each Tasso sample collection. Forty-eight hours after sample 
collection participants will be asked if they experienced any adverse events including 
bruising, bleeding, and/or signs of infection. Analyses will be performed for all subjects 
who provided at least one blood sample. 
6.3 Time and Events Table 
 
 
Part 1:  
Visit Description 
Screening 
Visit 1 
Visit 2* 
Time point 
Day 0 
Day 1 
Day 2 
Visit Window 
±14 days 
 
± 7 days 
Eligibility 
X 
 
 
Hgb/Hcta 
 
X 
X 
Tacrolimus trougha  
(venipuncture-clinical lab) 
 
X 
X 
Tacrolimus troughb  
(venipuncture- PK Core) 
 
X 
X 
Tacrolimus trough  
(capillary, Tasso & Mitra- PK Core) 
 
X 
X 
Mycophenolate trough  
(venipuncture- clinical lab) 
 
X 
X 
Mycophenolate troughb  
(venipuncture- PK Core) 
 
X 
X 
Mycophenolate trough  
(capillary, Tasso & Mitra- PK Core) 
 
X 
X 
Ganciclovir concentrationc  
(venipuncture- PK core) 
 
 
 
Ganciclovir concentrationc 
(capillary, Tasso & Mitra- PK Core) 
 
 
 
Questionnaire  
 
X 
X 

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*Visit 2 will occur if the following criteria are met:  
 
1. Patient remains admitted to the hospital and study inclusion criteria continue to be met 
2. A second standard of care tacrolimus trough concentration is ordered by the clinical team 
Failure to collect samples for visit 2 will not be considered a protocol deviation.   
aHgb/Hct and tacrolimus trough values from the clinical lab will be obtained from standard of care labs 
bAnalysis will only be completed if leftover blood is available to be obtained from the clinical lab after 
completion of all ordered/standard of care labs 
c Analysis of ganciclovir will only be completed if the participant is receiving ganciclovir or valganciclovir 
as part of their standard of care. Adidtion of ganciclovir to the analysis will not change the volume of blood 
collected.  
 
Visit Description 
Screening  
Baseline 
Home 
collect 1 
Home 
collect 2 
Visit 3a 
Time point 
Day -14  
Day 0 
Day 14 
Day 56 
Day60 
Visit Window 
±14 days 
±14 day 
±14 days 
±14 days 
±28 days 
Informed Consent 
X 
 
 
 
 
Demographics 
X 
 
 
 
 
Eligibility 
X 
 
 
 
 
Height/Weight 
X 
 
 
 
 
Randomization 
 
X 
 
 
 
Education 
 
X 
 
 
 
Tacrolimus AUC  
(capillary- PK Core)b 
 
 
X 
X 
 
Mycophenolate  AUC 
(capillary- PK Core)b 
 
 
X 
X 
 
Questionnaire 1  
 
X 
 
 
 
Questionnaire 2 
 
 
 
X 
 
Concomitant Medication 
Review 
X 
 
 
 
 
Study Interventionc 
 
 
X 
X 
 
Drug Adherence 
Assessment 
 
 
 
X 
 
Subject Diary 
 
 
X 
X 
 
Ecological Momentary 
Assessments 
 
 
X 
X 
 
Qualitative interview 
 
 
 
 
X 
a. 
Visit 3 is only applicable to participants selected using maximum variation purposive sampling 
b. 
Consists of 4 collection events over 8 hours on each occasion (time 0, 1 hr, 4hr, and 8hr after the morning dose of tacrolimus and mycophenolate)  
c. 
Text messaging will begin 48 hours prior to the sample collection event and continues for 48 hours after sample collection 
7.0 ADVERSE EVENTS 
This is a pharmacokinetic study, but safety data will be collected on adverse and serious 
adverse events. 
7.1 Adverse Event Reporting Requirements 
Since the responsibility of the management of the patient’s transplant regimen is retained 
by the health care providers at the University of Michigan Transplant Center and not 
dictated by the study protocol, deaths and hospitalizations will typically not be study 
related. Serious adverse events (SAEs) and adverse events (AEs) that are related to the 
participant’s kidney transplant or other chronic disease conditions are not unanticipated 
and therefore will not be considered reportable to the IRB. For the sake of our study 
purposes and outcomes we will track SAEs and AEs related to study participation. 

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Adverse event data will be reviewed by the project leadership team and will be summarized 
in reports quarterly. Non-serious (mild/moderate) adverse event data will be reported to the 
IRB in annual renewals. SAEs related to study participation will be reported to the IRB 
within 7 calendar days of identification by the study team. A privacy violation or breach 
of confidentiality will be reported to the IRB within 7 calendar days and to the Corporate 
Compliance office within 24 hours of identification.  
 
Definition of Adverse Events (AEs): AEs that are of particular interest to our study and 
that we will specifically track include problems associated with capillary sampling 
(infection, bruising, and bleeding at the site of lancet puncture) and text message 
communication (privacy breach). Capillary sampling AEs will be assessed at 48 hours after 
collection via text message requesting patients to self-report (Table 1). We will also assess 
for hospitalizations, urgent care/emergency room visits, and death. These events will be 
collected via electronic record review or self-report.  
 
The severity or grade of an adverse event may be measured using the following definitions: 
Mild:  Noticeable to the subject, but does not interfere with subject’s expected daily 
activities, usually does not require additional therapy or intervention, dose 
reduction, or discontinuation of the study. 
 
Moderate:  Interferes with the subject’s expected daily activities, may require some 
additional therapy or intervention but does not require discontinuation of the study. 
 
Severe: Extremely limits the subject’s daily activities and may require 
discontinuation of study therapy, and/or additional treatment or intervention to 
resolve. 
 
The investigator or co-investigator is responsible for assignment of attribution. 
Definite – The AE is clearly related to the study intervention. 
Probable – The AE is likely related to the study treatment/intervention. 
Possible – The AE may be related to the study treatment/intervention. 
Unlikely – The AE is doubtfully related to the study treatment/intervention. 
Unrelated – The AE is clearly NOT related to the study treatment/intervention. 
 
7.2 Reporting of Unanticipated Problems 
There are types of incidents, experiences, and outcomes that occur during the conduct of 
human subjects research that represent unanticipated problems but are not considered 
adverse events. For example, some unanticipated problems involve social or economic 
harm instead of the physical or psychological harm associated with adverse events. In other 
cases, unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. Unanticipated problems that are related to the study and indicate risk to 
subjects and are not also SAEs will be reported the IRB within 14 calendar days.  
 

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Unanticipated problem: Per FDA Procedural Guidance for Clinical Investigators, 
Sponsors, and IRBs (January 2009), an unanticipated problem is defined as a 
serious problem that has implications for the conduct of the study (requiring a 
significant and usually safety-related, change in the protocol (such as revising 
inclusion/exclusion criteria or including a new monitoring requirement), informed 
consent or investigator’s brochure). 
 
Upon becoming aware of any incident, experience, or outcome (not related to an 
adverse event) that may represent an unanticipated problem, the investigator should 
assess whether the incident, experience, or outcome represents an unanticipated 
problem. The incident, experience, or outcomes is considered unanticipated if it 
meets all of the following criteria: 
 
1. Unexpected (in terms of nature, severity, or frequency); 
2. Related or possibly related to participation in the research; and 
3. Suggests that the research places subjects or others at a greater risk of harm than 
was previously known or recognized. 
 
Unanticipated problem Reporting: Per 21 CFR 312.66, 312.53 (c)(1)(vii), and 
56.108(b)(1), should an Unanticipated problem occur during the investigation, the 
investigator will promptly report all unanticipated problems involving risks to 
human subjects or others to the IRB. 
7.3 Reporting of Pregnancy 
Pregnancy status will not be assessed during this study. The interventions of this study are 
not expected to cause pregnancy-related harm.  
 
Participants enrolled in this study are receiving mycophenolate as the standard of care and 
not as a study intervention. Women of childbearing potential receive education on the risk 
of mycophenolate during pregnancy at the time of therapy initiation as mandated by the 
US Food and Drug Administration (FDA) Mycophenolate Risk Evaluation and Mitigation 
Strategy (REMS). Participants of childbearing potential will be provided with 
reinforcement of the REMS education during the informed consent process. If pregnancy 
occurs and mycophenolate is discontinued at the discretion of the treating physician, the 
study intervention will also be discontinued as stated in section 5.4.  
8.0 DEVICE INFORMATION  
The Tasso OnDemand is a sterile, disposable, integrated capillary blood collection device, 
including a lancet assembly and a detachable reservoir for the collection of blood.  
The Tasso-M20 is used for the self-collection and storage of capillary blood from 
minimally trained users and shipping to a central laboratory for analysis. This configuration 
is available commercially and is registered with the FDA as a class 1 blood collection and 
container system. Tasso, Inc has validated the device utilizing the safety, sterility, 
packaging, and biocompatibility test methods required by the FDA for a medical device 
that interfaces with the body for less than 24 hours.  
 

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The mechanism is very simple to operate and enables the collection of a blood sample at 
the press of button. The device is placed on the skin of the upper arm and remains in 
position using an adhesive backing. The device is actuated by pressing the central button, 
causing an internal spring to contract and a plunger, containing a single 16-gauge stainless-
steel lancet which penetrates 2.5mm into the skin. Upon actuation of the device, the lancet 
penetrates the skin, is immediately retracted (does not remain deployed for the whole wear 
time), and locks in an inactive position to prevent re-use. The lancet puncture causes blood 
to pool on the surface of the skin, which is further enhanced by the small amount of vacuum 
(~40 kPa). The base of the device is designed to collect the blood pooling on the surface of 
the skin and channel the blood into a detachable reservoir. The blood collection is stopped 
after the blood reaches an indicator on the reservoir (fill window for the dried blood 
configuration for a total sample of 80µL). 
 
Risk analysis has been performed in accordance with ISO 14971. Risk Management Report 
Risks associated with use of the Tasso OnDemand are expected to be similar to those of 
other blood collection device, including risks related to the infection, pain and loss of 
sample integrity. The 40 kPa vacuum enhances the blood draw while reducing negative 
effects on the skin, such as hematomas or marks. Typically, a small mark, similar to those 
left by fingerstick devices, remains on the skin for 24-48 hours. Rarely, slight bruising is 
observed that does not lead to other negative consequences. The device presents minimal 
risk to the subjects in the study as the procedures involved are common lancet punctures. 
The device has been applied on over 50,000 subjects since 2014 without any adverse events 
recorded. 
 
The Tasso-M20 is supplied to participants as part of a kit including the device in a sterile 
pouch, alcohol pad, bandage, instruction sheet, specimem bag/return pouch with moisture 
absorpting packs, and box for mailing. Each device is single use.  
 
The Mitra is a separate specimen collector for the storage and transport of biological fluids. 
To obtain the capillary blood, a sterile single use, contact activiated safety lancet will be 
used.  
9.0 STATISTICAL CONSIDERATIONS 
This section presents a summary of the planned statistical analyses.  
9.1 Study Design/Study Outcome Measures 
Part 1: This study is a clinical validation for the comparison of bioanalytical methods.   
 
Part 2: This study is a prospective, randomized, pilot evaluation of a text messaging 
intervention to facilitate self-collection of dried blood samples for tacrolimus and 
mycophenolate therapeutic drug monitoring.  
9.2 Primary Objective (Part 2) 
9.2.1 To compare the effect of bidirectional text communication on adherence to 
and accuracy of home-based AUC collection versus unidirectional text 

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reminders in kidney transplant recipients receiving tacrolimus and 
mycophenolate. 
 
Primary Outcome Measure: successful home-based TDM defined as the 
timely receipt of samples that are adequate for pharmacokinetic analysis.  
 
Samples will be considered timely if post-marked within 48 hours of 
planned sample collection. Samples will be considered adequate for 
analysis if all 4 sample collections are documented within the designated 
sample collection window.  
9.3 Secondary Objectives (Part 1) 
 
9.3.1 To assess the bioanalytical agreement of two sample collection methods (dried 
blood spot and venipuncture) as measured by Liquid Chromatography with 
tandem mass spectrometry (LC-MS/MS). 
 
Secondary Outcome Measure: difference between drug concentrations 
measured from concurrent dried blood spot and venipuncture samples.  
9.4 Exploratory Objectives 
 
9.4.1 To evaluate the predictive performance of a mycophenolate matrix conversion 
equation. (Part 1) 
 
Exploratory Outcome Measure: median percentage predictive error and 
median absolute predictive error 
 
9.4.2 To assess the bioanalytical agreement of two sample collection methods (dried 
blood spot and venipuncture) as measured by LC-MS/MS assay at the 
University of Michigan PK Core and Michigan Medicine Clinical laboratory. 
(Part 1) 
 
Exploratory Outcome Measure: difference between drug concentrations 
measured from the two LC-MS/MS assays. 
 
9.4.3 To evaluate participant characteristics based on the Theoretical Domains 
Framework associated with successful home-based TDM. (Part 2) 
 
Exploratory Outcome Measure: The relationship between patient 
characteristics and successful home-based TDM 
9.5 Sample Size and Accrual 
Part 1: The expected LC-MS/MS assay coefficient of variation (CV) of >5% with a range 
ratio of >25 requires 40 participants with 80 paired dried and venous samples (2 pairs from 
each participant) to clinically validate the assay, including validation of the anticipated 

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mycophenolate conversion factor.42, 43 To account for participants unwilling to provide 
additional samples, up to 90 participants may be enrolled. 
 
Part 2: Compared to the previous rate for successful sample collection of 55% reported in 
the literature, the selected sample size of 45 participants will provide this pilot study >90% 
power to detect a 25% difference in successful sample collection (anticipated overall 
success of 80% in both groups). 
 
The sample size is also adequate to assess the secondary and exploratory outcomes. 
Additionally, the 45 participants will provide 80% power for a 95% confidence interval to 
identify a 10-point difference in the absolute prediction error (APE) between AUC 
calculated from all 4 samples and estimates using different sampling combinations for 
tacrolimus. Finally, the convenience sample of the included patients will be used for the 
quantitative analysis to provide preliminary data describing the relationships between 
Theoretical Domain constructs and successful competition of home-based TDM. 
Qualitative interviews will be conducted with a minimum of 10 participants or until data 
saturation is reached. 
 
Subjects will be considered evaluable if they complete the baseline survey and attempt to 
complete at least 1 home AUC collection.  
9.6 Data Analyses Plan 
9.6.1 Primary Objective- To compare the effect of bidirectional text 
communication on adherence to and accuracy of home-based AUC 
collection versus unidirectional text reminders in kidney transplant 
recipients receiving tacrolimus and mycophenolate. 
 
Primary Outcome Measure: successful home-based TDM defined as the 
timely receipt of samples that are adequate for pharmacokinetic analysis.  
 
Samples will be considered timely if post-marked within 48 hours of 
planned sample collection. Samples will be considered adequate for 
analysis if all 4 sample collections are documented within the designated 
sample collection window.  
 
The primary endpoint between the study groups will be compared using the 
chi-squared test. Comparisons of demographic and clinical characteristics 
between successful and unsuccessful participants will be made. A 
multivariable logistic regression will also be completed, where the primary 
independent variable is the study group, controlled for age, sex, and time 
since transplant. The latter analyses will explore factors that may impact 
adherence to sampling. 
 
9.6.2 Secondary Objectives - To assess the bioanalytical agreement of two 
sample collection methods (dried blood spot and venipuncture) as measured 
by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). 

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Secondary Outcome Measure: difference between drug concentrations 
measured from concurrent dried blood spot and venipuncture samples.  
 
Passing-Bablok regression will be used to measure the linear relationship 
between the drug concentrations obtained in venipuncture and dried 
capillary samples. Bland-Altman plots will be used to assess agreement and 
estimate bias. Acceptance criteria will be in accordance with the Food and 
Drug Administration (FDA) Bioanalytical Method Validation.42 Drug 
concentrations from dried blood spots must be within ±15% of venipuncture 
value in ≥67% of samples.   
 
9.6.3 Exploratory Objectives 
a. To evaluate the predictive performance of a mycophenolate matrix 
conversion equation.  
 
Exploratory Outcome Measure: median percentage predictive error and 
median absolute predictive error 
 
The predictive performance of the anticipated mycophenolate matrix 
conversion equation will be estimated using the median percentage 
predictive error (MPPE) and median absolute percentage predictive error 
(MAPE) to provide measures of bias and imprecision.  
 
b. To assess the bioanalytical agreement of two sample collection methods 
(dried blood spot and venipuncture) as measured by LC-MS/MS assay 
at the University of Michigan PK Core and Michigan Medicine Clinical 
laboratory. 
 
Exploratory Outcome Measure: difference between drug concentrations 
measured from the two LC-MS/MS assays. 
 
Passing-Bablok regression will be used to measure the linear relationship 
between the drug concentrations obtained in venipuncture and dried 
capillary samples. Bland-Altman plots will be used to assess agreement and 
estimate bias. Acceptance criteria will be in accordance with the Food and 
Drug Administration (FDA) Bioanalytical Method Validation.42 Drug 
concentrations from dried blood spots must be within ±15% of venipuncture 
value in ≥67% of samples.   
 
c. To evaluate participant characteristics based on the Theoretical Domains 
Framework associated with successful home-based TDM.  
 
Exploratory Outcome Measure: The relationship between patient 
characteristics and successful home-based TDM 
 

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For the quantitative analysis, the dependent variable will be successful 
home-based TDM defined as the timely receipt of samples that are adequate 
for pharmacokinetic analysis. The survey constructs, reminder group, and 
patient demographics will be independent variables compared between 
groups. For the qualitative analysis, an abductive approach to data coding 
will be taken using the Theoretical Domain Framework, but themes 
identified outside of the framework will be further developed. Method 
triangulation of interview and survey data will be conducted. Joint Display 
principles will be applied to integrate the results.57 
10. DATA AND SAFETY MONITORING 
As this study utilizes capillary blood sampling obtained via lancet (similar to monitoring 
done by patients undergoing self-monitoring of blood glucose) and reminder text messages 
with no PHI identifiers in conjunction with standard transplant management by the 
patients’ established treating health care provider, this study is expected to pose no greater 
than minimal risk and therefore a data safety and monitoring board will not be used.  
 
Participants will be asked about adverse events following sample collection as outlined 
previously. The text messages logs will be reviewed at the time of anticipated responses 
by the study team for complications requiring intervention.  
 
The study team will meet at least quarterly to discuss matters related to: 
• Enrollment rate relative to expectations, characteristics of participants 
• Safety of study participants (Serious Adverse Event & Adverse Event reporting) 
• Adherence to protocol (protocol deviations) 
• Completeness, validity and integrity of study data 
• Retention of study participants 
11.  QUALITY ASSURANCE AND AUDITS 
a. Audits and Inspections 
A regulatory authority may also wish to conduct an inspection of the study, during its 
conduct or even after its completion. If an inspection has been requested by a regulatory 
authority, the study staff must immediately inform IRB, Medical School Regulatory 
Affairs, and MIAP.  
b. Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, or Manual of 
Procedures (MOP) requirements. The noncompliance may be either on the part of the 
subject, the investigator, or the study site staff. As a result of deviations, corrective actions 
are to be developed by the site and implemented promptly.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify and 
report major deviations within 7 calendar days of identification of the protocol deviation 
to the IRB. A major deviation is defined as that may adversely impact safety of participants 

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or a pattern of minor protocol deviations which suggest a systematic problem that may 
place subjects or others at greater risk of harm. Other minor deviations will be reported to 
the IRB at the time of continuing review. Missed or out of window laboratory collections 
will not be considered deviations as one objective of this study is to understand the 
feasibility of this approach in real world settings where patients may modify their lab 
collection schedule against the advice of their medical provider. Out of window collection 
of study specific labs are not expected to influence patient safety. The timing of labs in 
relation to the study window is included as an outcome variable. Patients whose anticipated 
sample is not received within the study window will be contacted via telephone by study 
staff to obtain the sample in an effort to maintain sample size for the secondary and 
exploratory aims but will be classified as unsuccessful for the primary endpoint. If samples 
from home collection 1 are still not received after the initial call, the patient will not be 
contacted again until after the 2nd scheduled home-collection to allow for a washout period 
to assess the adherence with the second set of text messages. 
12. REGULATORY 
a. Institutional Review Board (IRB) 
Before implementing this study, the protocol, the proposed informed consent form, and 
other information to be provided to subjects, must be reviewed and approved by a properly 
constituted IRB. Any amendments to the protocol must be reviewed and approved by the 
IRB. 
b. Subject Information and Consent 
Study team member will explain to each subject (or legally authorized representative) the 
nature of the study, its purpose, the procedures involved, the expected duration, the 
potential risks and benefits involved and any discomfort it may entail.  Each subject will 
be informed that participation in the study is voluntary and that he/she may withdraw from 
the study at any time and that withdrawal of consent will not affect his/her subsequent 
medical treatment or relationship with the treating physician. 
 
This informed consent will be given by means of a standard written statement, written in 
non-technical language. The subject should read and consider the statement before signing 
and dating it and will be given a copy of the signed document. If the subject cannot read or 
sign the documents, oral presentation may be made or signature given by the subject’s 
legally appointed representative, if witnessed by a person not involved in the study, 
mentioning that the subject could not read or sign the documents. No subject can enter the 
study before his/her informed consent has been obtained. 
 
To support patient preference and reduce travel burden, consent can be completed in-
person or remotely. If done remotely, to ensure participants have the opportunity for 
discussions with the study team a video conference (Zoom Health) or telephone call will 
be used prior to documenting consent. Participants will be reminded to use a private 
location to help ensure privacy and confidentiality during the discussion. Electronic 
informed consent using SignNow will preferentially be used for all participants to facilitate 
remote consent. Following completion, participants will be provided a signed copy of the 

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consent via email or mail (as requested by the participant). If participants are unable to use 
SignNow, they will be provided with the informed consent via mail, email, or other 
method. The participant will return the signed informed consent form in the manner most 
feasible for them, including by mail, fax, email, or as an electronic image.  Upon receipt of 
the signed document, the study team member will also sign the document, document the 
informed consent was obtained, and mail or email the completed, signed form to the 
participant.  
 
The informed consent form is considered to be part of the protocol and will be submitted 
for IRB approval. 
 
13. REFERENCES 
1. 
Wolfe RA, Ashby VB, Milford EL, et al. Comparison of mortality in all patients on 
dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric 
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2. 
Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2018 Annual Data Report: Kidney. 
American Journal of Transplantation. 2020;20(s1):20-130. doi:10.1111/ajt.15672 
3. 
Axelrod DA, Schnitzler MA, Xiao H, et al. An economic assessment of contemporary 
kidney transplant practice. Am J Transplant. May 2018;18(5):1168-1176. doi:10.1111/ajt.14702 
4. 
Sussell J, Silverstein AR, Goutam P, et al. The economic burden of kidney graft failure in 
the United States. Am J Transplant. May 2020;20(5):1323-1333. doi:10.1111/ajt.15750 
5. 
Lamb KE, Lodhi S, Meier-Kriesche HU. Long-term renal allograft survival in the United 
States: a critical reappraisal. Am J Transplant. Mar 2011;11(3):450-62. doi:10.1111/j.1600-
6143.2010.03283.x 
6. 
Van Loon E, Senev A, Lerut E, et al. Assessing the Complex Causes of Kidney Allograft 
Loss. Transplantation. Feb 20 2020;doi:10.1097/tp.0000000000003192 
7. 
Neuberger JM, Bechstein WO, Kuypers DR, et al. Practical Recommendations for Long-
term Management of Modifiable Risks in Kidney and Liver Transplant Recipients: A Guidance 
Report and Clinical Checklist by the Consensus on Managing Modifiable Risk in Transplantation 
(COMMIT) Group. Transplantation. Apr 2017;101(4S Suppl 2):S1-s56. 
doi:10.1097/tp.0000000000001651 
8. 
Sellarés J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant 
failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 
Feb 2012;12(2):388-99. doi:10.1111/j.1600-6143.2011.03840.x 
9. 
Tong A, Sautenet B, Chapman JR, et al. Research priority setting in organ 
transplantation: a systematic review. Transpl Int. Apr 2017;30(4):327-343. doi:10.1111/tri.12924 
10. 
Knight SR, Metcalfe L, O’Donoghue K, et al. Defining Priorities for Future Research: 
Results of the UK Kidney Transplant Priority Setting Partnership. PLOS ONE. 
2016;11(10):e0162136. doi:10.1371/journal.pone.0162136 
11. 
Metz DK, Holford N, Kausman JY, et al. Optimizing Mycophenolic Acid Exposure in 
Kidney Transplant Recipients: Time for Target Concentration Intervention. Transplantation. Oct 
2019;103(10):2012-2030. doi:10.1097/tp.0000000000002762 
12. 
Hale MD, Nicholls AJ, Bullingham RE, et al. The pharmacokinetic-pharmacodynamic 
relationship for mycophenolate mofetil in renal transplantation. Clin Pharmacol Ther. Dec 
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13. 
van Gelder T, Hilbrands LB, Vanrenterghem Y, et al. A randomized double-blind, 
multicenter plasma concentration controlled study of the safety and efficacy of oral 
mycophenolate mofetil for the prevention of acute rejection after kidney transplantation. 
Transplantation. Jul 27 1999;68(2):261-6. doi:10.1097/00007890-199907270-00018 
14. 
Le Meur Y, Büchler M, Thierry A, et al. Individualized mycophenolate mofetil dosing 
based on drug exposure significantly improves patient outcomes after renal transplantation. Am J 
Transplant. Nov 2007;7(11):2496-503. doi:10.1111/j.1600-6143.2007.01983.x 
15. 
Undre NA, van Hooff J, Christiaans M, et al. Low systemic exposure to tacrolimus 
correlates with acute rejection. Transplant Proc. Feb-Mar 1999;31(1-2):296-8. 
doi:10.1016/s0041-1345(98)01633-9 
16. 
Wong DD, van Zuylen WJ, Novos T, et al. Detection of Ganciclovir-Resistant 
Cytomegalovirus in a Prospective Cohort of Kidney Transplant Recipients Receiving 
Subtherapeutic Valganciclovir Prophylaxis. Microbiol Spectr. Jun 29 2022;10(3):e0268421. 
doi:10.1128/spectrum.02684-21 
17. 
Franck B, Autmizguine J, Marquet P, Ovetchkine P, Woillard JB. Pharmacokinetics, 
Pharmacodynamics, and Therapeutic Drug Monitoring of Valganciclovir and Ganciclovir in 
Transplantation. Clin Pharmacol Ther. Aug 2022;112(2):233-276. doi:10.1002/cpt.2431 
18. 
Leino AD, Pai MP. Maintenance Immunosuppression in Solid Organ Transplantation: 
Integrating Novel Pharmacodynamic Biomarkers to Inform Calcineurin Inhibitor Dose Selection. 
Clin Pharmacokinet. Jul 27 2020;doi:10.1007/s40262-020-00923-w 
19. 
Kiang TKL, Ensom MHH. Exposure-Toxicity Relationships of Mycophenolic Acid in 
Adult Kidney Transplant Patients. Clinical Pharmacokinetics. 2019/12/01 2019;58(12):1533-
1552. doi:10.1007/s40262-019-00802-z 
20. 
Zwart TC, Gokoel SRM, van der Boog PJM, et al. Therapeutic drug monitoring of 
tacrolimus and mycophenolic acid in outpatient renal transplant recipients using a volumetric 
dried blood spot sampling device. Br J Clin Pharmacol. Dec 2018;84(12):2889-2902. 
doi:10.1111/bcp.13755 
21. 
Martial LC, Aarnoutse RE, Schreuder MF, Henriet SS, Brüggemann RJM, Joore MA. 
Cost Evaluation of Dried Blood Spot Home Sampling as Compared to Conventional Sampling 
for Therapeutic Drug Monitoring in Children. PLOS ONE. 2016;11(12):e0167433. 
doi:10.1371/journal.pone.0167433 
22. 
Veenhof H, van Boven JFM, van der Voort A, Berger SP, Bakker SJL, Touw DJ. Effects, 
costs and implementation of monitoring kidney transplant patients' tacrolimus levels with dried 
blood spot sampling: A randomized controlled hybrid implementation trial. Br J Clin Pharmacol. 
Jul 2020;86(7):1357-1366. doi:10.1111/bcp.14249 
23. 
Keevil BG, Tierney DP, Cooper DP, Morris MR, Machaal A, Yonan N. Simultaneous 
and rapid analysis of cyclosporin A and creatinine in finger prick blood samples using liquid 
chromatography tandem mass spectrometry and its application in C2 monitoring. Ther Drug 
Monit. Dec 2002;24(6):757-67. doi:10.1097/00007691-200212000-00013 
24. 
Leichtle AB, Ceglarek U, Witzigmann H, Gäbel G, Thiery J, Fiedler GM. Potential of 
dried blood self-sampling for cyclosporine c(2) monitoring in transplant outpatients. J 
Transplant. 2010;2010:201918. doi:10.1155/2010/201918 
25. 
Koster RA, Botma R, Greijdanus B, et al. The performance of five different dried blood 
spot cards for the analysis of six immunosuppressants. Bioanalysis. 2015;7(10):1225-35. 
doi:10.4155/bio.15.63 

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26. 
Veenhof H, Koster RA, Brinkman R, et al. Performance of a web-based application 
measuring spot quality in dried blood spot sampling. Clin Chem Lab Med. Nov 26 
2019;57(12):1846-1853. doi:10.1515/cclm-2019-0437 
27. 
Al-Uzri A, Freeman KA, Wade J, et al. Longitudinal study on the use of dried blood 
spots for home monitoring in children after kidney transplantation. Pediatr Transplant. Sep 
2017;21(6)doi:10.1111/petr.12983 
28. 
Gallant J, Wichart J, Kiang TKL. Predictability of Capillary Blood Spot Toward Venous 
Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus in Solid Organ 
Transplant Recipients. Eur J Drug Metab Pharmacokinet. Dec 2019;44(6):729-741. 
doi:10.1007/s13318-019-00553-z 
29. 
Vethe NT, Gustavsen MT, Midtvedt K, et al. Tacrolimus Can Be Reliably Measured 
With Volumetric Absorptive Capillary Microsampling Throughout the Dose Interval in Renal 
Transplant Recipients. Ther Drug Monit. Oct 2019;41(5):607-614. 
doi:10.1097/ftd.0000000000000655 
30. 
Gustavsen MT, Midtvedt K, Vethe NT, Robertsen I, Bergan S, Åsberg A. Tacrolimus 
area under the concentration versus time curve monitoring, using home-based volumetric 
absorptive capillary microsampling. Therapeutic Drug Monitoring. 2020;42(3):407-414.  
31. 
Mbughuni MM, Stevens MA, Langman LJ, et al. Volumetric Microsampling of Capillary 
Blood Spot vs Whole Blood Sampling for Therapeutic Drug Monitoring of Tacrolimus and 
Cyclosporin A: Accuracy and Patient Satisfaction. J Appl Lab Med. May 1 2020;5(3):516-530. 
doi:10.1093/jalm/jfaa005 
32. 
Vincze I, Rudge J, Vásárhelyi B, Karvaly GB. Analysis of 14 drugs in dried blood 
microsamples in a single workflow using whole blood and serum calibrators. Bioanalysis. Sep 
2020;12(17):1243-1261. doi:10.4155/bio-2020-0179 
33. 
Scuderi CE, Parker SL, Jacks M, et al. Kidney transplant recipient’s perceptions of blood 
testing through microsampling and venepuncture. Bioanalysis. 2020;12(13):873-881. 
doi:10.4155/bio-2020-0057 
34. 
Thakkar J, Kurup R, Laba TL, et al. Mobile Telephone Text Messaging for Medication 
Adherence in Chronic Disease: A Meta-analysis. JAMA Intern Med. Mar 2016;176(3):340-9. 
doi:10.1001/jamainternmed.2015.7667 
35. 
Browning RB, McGillicuddy JW, Treiber FA, Taber DJ. Kidney transplant recipients' 
attitudes about using mobile health technology for managing and monitoring medication therapy. 
Journal of the American Pharmacists Association : JAPhA. Jul-Aug 2016;56(4):450-454.e1. 
doi:10.1016/j.japh.2016.03.017 
36. 
McKenzie RB, Berquist WE, Foley MA, Park KT, Windsheimer JE, Litt IF. Text 
Messaging Improves Participation in Laboratory Testing in Adolescent Liver Transplant 
Patients. Journal of participatory medicine. 2015;7:e7.  
37. 
Gruber-Baldini AL, Velozo C, Romero S, Shulman LM. Validation of the PROMIS(®) 
measures of self-efficacy for managing chronic conditions. Qual Life Res. Jul 2017;26(7):1915-
1924. doi:10.1007/s11136-017-1527-3 
38. 
Hahn EA, DeWalt DA, Bode RK, et al. New English and Spanish social health measures 
will facilitate evaluating health determinants. Health Psychol. May 2014;33(5):490-9. 
doi:10.1037/hea0000055 
39. 
Ziegelmann JP, Griva K, Hankins M, et al. The Transplant Effects Questionnaire 
(TxEQ): The development of a questionnaire for assessing the multidimensional outcome of 

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organ transplantation - example of end stage renal disease (ESRD). Br J Health Psychol. Nov 
2002;7(Part 4):393-408. doi:10.1348/135910702320645381 
40. 
Rosaasen N, Taylor J, Blackburn D, Mainra R, Shoker A, Mansell H. Development and 
Validation of the Kidney Transplant Understanding Tool (K-TUT). Transplant Direct. Mar 
2017;3(3):e132. doi:10.1097/txd.0000000000000647 
41. 
Weiner BJ, Lewis CC, Stanick C, et al. Psychometric assessment of three newly 
developed implementation outcome measures. Implementation Science. 2017/08/29 
2017;12(1):108. doi:10.1186/s13012-017-0635-3 
42. 
Capiau S, Veenhof H, Koster R, et al. Official International Association for Therapeutic 
Drug Monitoring and Toxicology guideline: Development and Validation of Dried Blood Spot-
based Methods for Therapeutic Drug Monitoring. Therapeutic Drug Monitoring. 06/01 
2019;41:1. doi:10.1097/FTD.0000000000000643 
43. 
Linnet K. Necessary sample size for method comparison studies based on regression 
analysis. Clin Chem. Jun 1999;45(6 Pt 1):882-94.  
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Huijg JM, Gebhardt WA, Crone MR, Dusseldorp E, Presseau J. Discriminant content 
validity of a theoretical domains framework questionnaire for use in implementation research. 
Implementation Science. Jan 2014;911. doi:10.1186/1748-5908-9-11 
45. 
Atkins L, Francis J, Islam R, et al. A guide to using the Theoretical Domains Framework 
of behaviour change to investigate implementation problems. Implementation Science. 
2017/06/21 2017;12(1):77. doi:10.1186/s13012-017-0605-9 
46. 
Courtenay M, Rowbotham S, Lim R, Peters S, Yates K, Chater A. Examining influences 
on antibiotic prescribing by nurse and pharmacist prescribers: a qualitative study using the 
Theoretical Domains Framework and COM-B. BMJ Open. 2019;9(6):e029177. 
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47. 
Michie S, Johnston M, Abraham C, Lawton R, Parker D, Walker A. Making 
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48. 
Patton DE, Cadogan CA, Ryan C, et al. Improving adherence to multiple medications in 
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14. APPENDICES 
Appendix A: Contingency Operation Plan 
 
The following changes may be implemented and/or adapted without causing a deviation 
during a public health or civil emergency or restrictions. HOWEVER, the usual protocol 
parameters must be reinstated when the emergency is over or whenever local authorities 
and policies permit.  
 
It is important that specific information explaining the basis for missing data be recorded 
in the case report forms (indicating the relationship to the event/restrictions, as 
applicable).  
 
i. 
New subject enrollment 
Together with the study supporter University of Michigan, the Sponsor-Investigator 
will evaluate the new benefit/risk for subjects on the trial and determine if study 
enrollment needs to be partially or completely paused. 
 
ii. 
Study visit schedule 
The following adjustments will be permissible per clinician/subject discretion and 
institutional/government allowance:  
 
• Virtual or phone visits with the investigator will be allowed for all study visits.   
• Collection of samples are to be performed per clinician/subject discretion and lab 
facility capacity/capabilities. The study visit window will be extended by 90 days 
or until the participant’s provider deems laboratory assessment is clinically 
indicated.  
 
iii. 
Laboratory testing 
It may be possible that lab closure is required as a contingency measure during the 
course of a public health or civil emergency or restrictions. Should that occur: 
  
• Blood samples will not be collected unless they can be stored. 
• Patients will be allowed to have routine standard of care labs drawn at a 
local lab. The remaining specimen from the EDTA tube mailed to the 
University of Michigan for tacrolimus analysis per standard of care will be 
obtained for secondary use and analysis of tacrolimus concentrations by 
the PK Core.  
 
iv. 
Informed Consent Form (ICF) 
Consenting can be done virtually and digital signatures are allowed. 
 

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The study staff should communicate all changes to the research plan to the subject, as 
applicable, and must do so if the changes might affect the subject’s willingness to 
continue participation in the study. Communication can occur virtually or via an 
addendum to the informed consent as required by the IRB. If discussed, 
documentation of the discussion and the subject’s decision to continue/discontinue 
should be documented in the subject’s record. 
 
v. 
Statistical Analytics Plan: 
Should changes in the contingency operation plan and/or protocol lead to amending 
the statistical analysis plan for this study, consideration for doing so will include 
submission and/or consultation with the applicable committees and regulatory 
agencies for review.  
The plan for protocol deviations related to public health or civil emergency or 
restrictions will be assessed as part of the pre-specified analyses, and statistical 
procedures for handling these deviations will be addressed in the statistical analysis 
plan prior to database lock. Revisions to the statistical plan will be updated in the 
protocol and/or the statistical analysis plan, as required. 
 
vi. 
Monitoring 
Planned on-site monitoring visits may not be possible if the restrictions put in place 
limit travel and/or access to site location. As such, remote monitoring will be 
performed as necessary to maintain the defined monitoring schedule. 
 
vii. 
Safety and Protocol Deviation Reporting 
All safety and protocol deviation reporting for the study remains in place, per 
protocol requirements. Documentation of required reporting timelines are to be 
utilized during monitoring. 
 
 
 

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Appendix B. Study Instruments for subject-reported outcomes in Part 1 
We are interested in your own personal views of your experience having your blood sampled 
with the Tasso-M20 and Mitra devices.. 
First, we’d like you to think about how painful each sample method was to you. Indicate on a 
scale of 1 to 10, where 1 is no pain to 10 is the worst imagineable pain 
How painful was sampling from the vein (venipuncture)?  
 
 
 
 
 
 
 
 
 
 
No 
pain 
 
 
 
 
 
 
 
 
Worst 
pain 
 
How painful was sampling from the finger (Mitra)?  
 
 
 
 
 
 
 
 
 
 
No 
pain 
 
 
 
 
 
 
 
 
Worst 
pain 
 
How painful was sampling from the arm (Tasso)?  
 
 
 
 
 
 
 
 
 
 
No 
pain 
 
 
 
 
 
 
 
 
Worst 
pain 
 
Please rank the pain from most painful (1) to least painful (3) loaction. 
____ Vein (venipuncture) 
____Finger (Mitra) 
____Arm (Tasso) 
If you had to have multiple blood samples in a single day to monitor your immunosuppression, 
how many samples would you be willing to collect using each method (0 samples to 24 
samples)?  
Number of samples with the Tasso________ 
Number of samples with the Mitra________ 
Number of samples from the vein_________ 

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Now, we would like you to think about using these tools to collect blood samples to monitor 
your drug levels by yourself or with the help of your caregiver at home. Please indicate the 
extent to which you agree or disagree with these statements by ticking the appropriate box. 
First, we will ask about the Tasso-M20 self-collection tool. This tool samples from your arm. 
 
Completely 
disagree 
Disagree 
Neither agree 
nor disagree 
Agree Completely 
agree 
1. I think that I would like to 
collect my own samples 
frequently using the Tasso 
 
 
 
 
 
2. I found the Tasso self-
collection tool uncessarily 
complex 
 
 
 
 
 
3. I think the Tasso self-collection 
tool would be easy to use 
 
 
 
 
 
4. I think I would need the 
support of a technical person (like 
a nurse or phlebotomist) to be 
able to use the Tasso self-
collection tool 
 
 
 
 
 
5. I found the various functions in 
the Tasso tool were well 
integrated 
 
 
 
 
 
6. I thought there was too much 
inconsistency with the Tasso tool 
 
 
 
 
 
7. I imagine most people would 
learn to use the Tasso self-
collection tool very quickly 
 
 
 
 
 
8. I found the Tasso self-
collection tool to be very 
cumbersome to use 
 
 
 
 
 
9. I feel very confident that I 
could use Tasso the self-
collection tool 
 
 
 
 
 
10.  I would need to learn a lot of 
things before I could get going 
with the Tasso self-collection tool 
 
 
 
 
 

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Now think about using the Mitra tool. The Mitra tool samples the blood from a fingerprick. 
 
Completely 
disagree 
Disagree 
Neither agree 
nor disagree 
Agree Completely 
agree 
1. I think that I would like to 
collect my own samples 
frequently using the Mitra 
 
 
 
 
 
2. I found the Mitra self-
collection tool uncessarily 
complex 
 
 
 
 
 
3. I think the Mitra self-collection 
tool would be easy to use 
 
 
 
 
 
4. I think I would need the 
support of a technical person (like 
a nurse or phlebotomist) to be 
able to use the Mitra self-
collection tool 
 
 
 
 
 
5. I found the various functions in 
the Mitra tool were well 
integrated 
 
 
 
 
 
6. I thought there was too much 
inconsistency with the Mitra tool 
 
 
 
 
 
7. I imagine most people would 
learn to use the Mitra self-
collection tool very quickly 
 
 
 
 
 
6. I feel very confident that I 
could use Mitra the self-collection 
tool 
 
 
 
 
 
7.  I would need to learn a lot of 
things before I could get going 
with the Mitra self-collection tool 
 
 
 
 
 
 
Which tool would you prefer? 
Tasso (arm) Mitra 
(finger) 
Neither, I prefer sampling from my 
vein 
 

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Finally, we would like your thoughts about collecting drug levels at home overall. 
 
Completely 
disagree 
Disagree 
Neither 
agree 
nor 
disagree 
Agree 
Completely 
agree 
1. Home collection of drug levels meets 
my approval. 
 
 
 
 
 
2. Home collection of drug levels is 
appealing to me. 
 
 
 
 
 
3. I like home collection of drug levels. 
 
 
 
 
 
4. I welcome home collection of drug 
levels. 
 
 
 
 
 
5. Home collection of drug levels seems 
implementable. 
 
 
 
 
 
6. Home collection of drug levels seems 
possible 
 
 
 
 
 
7.  Home collection of drug levels 
seems doable. 
 
 
 
 
 
8. Home collection of drug levels seems 
easy to use. 
 
 
 
 
 
 
Do you already have experience with pricking yourself (for example with a blood glucose or 
INR measurement?) Yes   No 
 
Do you have any other comments or thoughts about the self-collection tools? 
____________________________________________________________________________________ 
____________________________________________________________________________________ 

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Appendix C: Study instruments for subject-reported outcomes in Part 2 
 
We are interested in your own personal views of how you now see your experience with your kidney 
transplant. These are statements other people have made about their transplant experience. Please indicate 
the extent to which you agree or disagree with these statements by ticking the appropriate box’. 
 
Completely 
disagree 
Disagree 
Neither 
agree nor 
disagree 
Agree 
Completely 
agree 
With regard to my transplant I feel that I am 
carrying around something fragile. 
 
 
 
 
 
I am hesitant to engage in certain activities 
because I am afraid of doing harm to my 
transplant 
 
 
 
 
 
I am worried about damaging my transplant 
 
 
 
 
 
I monitor my body more closely than before 
I had the transplant 
 
 
 
 
 
I worry each time my anti-rejection drug 
regimen is altered by my doctor 
 
 
 
 
 
I keep wondering how long my transplant 
will work 
 
 
 
 
 
I do not have any feelings of guilt toward 
the donor 
 
 
 
 
 
I feel guilty about having taken advantage of 
the donor 
 
 
 
 
 
The donor had to suffer to make me feel 
better 
 
 
 
 
 
Sometimes I think that I have ‘robbed’ the 
donor of a vital part 
 
 
 
 
 
I have the feeling that the donor/the donors’ 
family has some control over me 
 
 
 
 
 
I am uncomfortable with other people 
knowing that I have a transplant 
 
 
 
 
 
I have difficulty in talking about my 
transplant 
 
 
 
 
 
I avoid telling other people that I have a 
transplant 
 
 
 
 
 
Sometimes I think I do not need my anti-
rejection medicines 
 
 
 
 
 
Sometimes I forget to take my anti-rejection 
medicines 
 
 
 
 
 
I find it difficult to adjust to taking my 
prescribed anti-rejection drug-regimen 
 
 
 
 
 
When I am too busy, I may forget my anti-
rejection medicines 
 
 
 
 
 

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Page 37 
Sometimes I do not take my anti-rejection 
medicines 
 
 
 
 
 
I think that I have a responsibility to the 
transplant team to do well 
 
 
 
 
 
I feel that I owe the donor/the donor’s 
family something that I will never be able to 
repay 
 
 
 
 
 
I think that I have a responsibility to the 
donor/the donors’ family to do well 
 
 
 
 
 
I think that I have a responsibility to my 
friends and my family to do well 
 
 
 
 
 
 
People sometimes look to others for companionship, assistance, or other types of support. How often is 
each of the following kinds of support available to you if you need it? Choose one number from each line.  
 
None of 
the time 
A little 
of the 
time 
Some of 
the time 
Most of 
the time 
All of the 
time 
Someone you can count on to listen to you 
when you need to talk 
 
 
 
 
 
Someone to give you information to help 
you understand a situation 
 
 
 
 
 
Someone to give you good advice about a 
crisis 
 
 
 
 
 
Someone to confide in or talk to about 
yourself or your problems 
 
 
 
 
 
Someone whose advice you really want 
 
 
 
 
 
Someone to share your most private worries 
and fears with  
 
 
 
 
 
Someone to turn to for suggestions about 
how to deal with a personal problem  
 
 
 
 
 
Someone who understands your problems 
 
 
 
 
 
Someone to help you if you were confined 
to bed 
 
 
 
 
 
Someone to take you to the doctor if you 
needed it  
 
 
 
 
 
Someone to prepare your meals if you were 
unable to do it yourself 
 
 
 
 
 
Someone to help with daily chores if you 
were sick 
 
 
 
 
 
Someone who shows you love and affection 
 
 
 
 
 
Someone to love and make you feel wanted 
 
 
 
 
 
Someone to who hugs you 
 
 
 
 
 
Someone to have a good time with  
 
 
 
 
 
Someone to get together with for relaxation 
 
 
 
 
 

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Someone to do something enjoyable with  
 
 
 
 
 
Someone to do things with to help you get 
your mind off things  
 
 
 
 
 
 
Please respond to each question or statement by choosing one box per row that describes your CURRENT 
level of confidence. 
CURRENT level of confidence…  
I am not 
confident 
at all 
I am a 
little 
confident 
I am 
somewhat 
confident  
I am 
quite 
confident  
I am very 
confident  
I can follow directions when my doctor 
changes my medications  
 
 
 
 
 
I can take my medications when I am 
working or away from home 
 
 
 
 
 
I can take my medications when there is a 
change in my usual day (unexpected things 
happen) 
 
 
 
 
 
I can manage my medication without help 
 
 
 
 
 
I can remember to take my medication as 
prescribed  
 
 
 
 
 
I can use technology to help me 
management my medications and treatments 
(for example: to get information, avoid side 
effects, schedule reminders)  
 
 
 
 
 
I can list my medications, including the 
doses and schedule   
 
 
 
 
 
I can figure out what treatment I need when 
my symptoms change 
 
 
 
 
 
 
This next section ask you to answer some question about kidney transplant. Please fill out the questions as 
honestly as you can and do not look up any of the answers. Your responses are confidential, and the 
results will in no way impact your care.  
TRUE OR FALSE: CHOOSE THE BEST ANSWER 
1. Transplant pills must be taken to help prevent rejection.  
             □ True □ False 
2. Anti-rejection medications are also called immunosuppressants. 
             □ True □ False 
3. You should always take your anti-rejection medications unless instructed by your transplant 
team. 
             □ True □ False 
 

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4. You will need to do blood testing at least every 3 months for as long as the kidney transplant is 
functioning. 
             □ True □ False 
5. Herbal supplements are generally safe to take with your transplant, since they are natural. 
             □ True □ False 
 
CHECK THE CORRECT ANSWERS (YOU MAY CHOOSE MORE THAN ONE) 
6. When thinking about herbal or traditional therapies, which of the following are true? (check all 
the correct answers) 
___ Traditional treatments are safe for a kidney transplant because they are natural.  
___ Herbal medications recommended in the media (i.e., internet, TV) are generally safe for your 
transplant.  
___ Pills that boost your immune system are safe for people with a transplant.  
___ Family and friends may suggest herbal remedies or natural products - you should check with your 
transplant team before trying them out. 
 
7. Which statement are true regarding anti-rejection medication (check all the correct answers) 
___ Anti-rejection pills increase the risk of infection.  
___ Anti-rejection pills can be stopped if the kidney transplant is working well in ten years. 
___ Anti-rejection pills increase the risk of cancer.  
___ Anti-rejection pills can be stopped if side effects are too bad. 
___ Anti-rejection pills can sometimes be changed if side effects are too bad. 
 
8. If you are experiencing a side effect from your anti-rejection pills, what should you do? (check all 
the correct answers) 
___ Continue taking the pills as prescribed.  
___ Contact your transplant team.  
___ Decrease the dose of your anti-rejection pills to see if that helps.  
___ Stop your anti-rejection pills until you can see your doctor.  
___ Try to manage the side effects with over the counter medications. 
 
9. It is important to tell all your doctors that you received a kidney transplant because: (check all 
the correct answers) 
___ Other pills may not mix well with anti-rejection pills.  
___ Anti-rejection pills make it easier for you to catch infections.  
___ Anti-rejection pills increase your cancer risk, so regular checkups are important.  
___ Some pills may harm your transplant.  
___ Anti-rejection pills may affect how you heal after surgery.  

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Page 40 
___ You do not need to tell your doctors that you have a transplant. 
 
10. It is important to tell your pharmacist that you received a kidney transplant because: (check all 
the correct answers)  
___ Other pills may not mix well with anti-rejection pills.  
___ Your pharmacist can help you decide if you should treat common problems (like heartburn or (cold 
sores) with over the counter medications.  
___ Some over the counter medications can harm your transplant.  
___ You do not need to tell your pharmacist that you have a transplant. 
 
11. When thinking about transplant rejection, which of the following are true? (check all the 
correct answers)  
___ Rejection cannot be treated.  
___ Stronger anti-rejection pills can sometimes treat rejection.  
___ You have a good match, so rejection cannot occur.  
___ If you take your anti-rejection pills correctly, rejection will not occur.  
___ You will know if you have rejection because you will feel sick.  
 
12. Years after your kidney transplant, which of the following are true? (check all the correct 
answers)  
___ Some anti-rejection pills can hurt the kidney transplant.  
___ High blood pressure can hurt the kidney transplant.  
___ More pills may be needed to treat complications from the transplant.  
___ Your transplant team may decrease your anti-rejection pills.  
___ Your transplant team may need to increase your anti-rejection pills.  
 
We are interested in your own personal views of your experience using the Tasso-M20 device to 
obtain blood samples yourself. Please indicate the extent to which you agree or disagree with 
these statements by ticking the appropriate box. 
 
Completely 
disagree 
Disagree 
Neither 
agree 
nor 
disagree 
Agree 
Completely 
agree 
1. Home collection of drug levels meets 
my approval. 
 
 
 
 
 
2. Home collection of drug levels is 
appealing to me. 
 
 
 
 
 
3. I like home collection of drug levels. 
 
 
 
 
 

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Page 41 
4. I welcome home collection of drug 
levels. 
 
 
 
 
 
5. Home collection of drug levels seems 
implementable. 
 
 
 
 
 
6. Home collection of drug levels seems 
possible 
 
 
 
 
 
7.  Home collection of drug levels 
seems doable. 
 
 
 
 
 
8. Home collection of drug levels seems 
easy to use. 
 
 
 
 
 
 
 
 

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Appendix D: Interview Guide 
Table 3. Interview Guide for patients related to the Theoretical Domains Framework44-48 
COM-B 
Component 
Domain 
Interview Item 
Capability  
  
Knowledge 
Why is it important to monitor your immunosuppression? 
Tell me about how and when you obtain blood samples to monitor your immunosuppression. 
Do you know what your target tacrolimus level is?  
Can you give me some examples of what can increase or decrease your tacrolimus level? 
Would having more knowledge about why your transplant team asks that you obtain samples to 
monitor your immunosuppression make it more likely you'd be willing to collect the samples? What 
about collecting one sample vs multiple samples? 
Memory, attention and 
decision processes 
Is remembering to obtain samples to monitor your immunosuppression ever an issue? How often do 
you forget? 
Will you remember to obtain samples? How? Were the reminders helpful? What else would be 
helpful? 
How much attention will you have to pay to obtain samples at home vs the lab? 
When might you decide to not obtain samples? Would this be different if you could obtain more 
samples at home? 
Would you be willing to continue to obtain the multiple samples in the same day? What would make 
you more or less willing? What about increasing how often you obtain samples (i.e. obtain home 
samples monthly, lab q3)? 
Behavioral regulation 
Do you keep track of your overall kidney health including tacrolimus level? 
Are you aware of your day-to-day behavior as you work to keep your kidney healthy? 
Are there procedures or ways of thinking that would encourage home monitoring? 
Skills 
How helpful was the training you received on how to obtain blood samples at home? What would 
make it better? 
How easy or difficult was it to obtain the samples at home? What problems did you encounter? What 
would help? 
Do you know how to check your results via the online portal?  
What additional skills do you or your fellow transplant recipients need to obtain samples at home? 
Opportunity 
Environmental context 
and resources 
Are there competing tasks or time constraints to monitoring? Do you think this would change if you 
could obtain samples at home and have fewer visits to the lab? 

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Where did you obtain the samples (home, work, etc)? Did anything in your environment affect whether 
you were able to obtain samples? Would you be able to do it in a different location if needed? 
Did you have the necessary resources to perform the home sampling? What resources additional 
resources would help? 
How did the tools you were given (sample kit and reminders) help you obtain home samples?  
Social influences 
Do the people who are important to you think you should monitor your immunosuppression? 
Did the people around you ever affect your ability to obtain samples (either at home or at the lab)? 
Do you have the support from other people you need to perform home sampling? (family, friends, 
provider) How do these people help you? What might make their support more or less important?  
Motivation  
Social role and 
identity 
Do you believe you have a responsibility to complete the recommended monitoring? Why? 
Beliefs about 
capabilities 
How confident are you that you can obtain samples despite difficulties? (little time, conflicting 
demands) 
How capable would you feel if you were asked to continue to obtain samples at home? How long do 
you think would you feel capable? 
How well equipped did you feel to obtain the samples? 
How optimistic are you that monitoring your immunosuppression will help maintain your health? 
Beliefs about 
consequences 
What do you think will happen if you do not complete immunosuppression monitoring? 
(positive/negative, short/long term) 
Do you think monitoring your immunosuppression is a good thing? Why? 
How much difference do you think more frequent or complete data on your immunosuppression levels 
will make in your care? Why? 
What are the costs or negative consequences of monitoring your immunosuppression? (financial, time, 
personal) Would home-monitoring reduce these costs? What are consequences if you do not monitor 
your immunosuppression? 
Motivation and goals 
How much do you want to obtain samples to monitor immunosuppression? Is this different with 
venipuncture compared to home samples? (willing to do more with home samples?) 
How much of priority is monitoring your immunosuppression to you? What would make it more or 
less of a priority?  
Are there other things you want to do or achieve that might interfere with monitoring? Is this different 
with venipuncture compared to home samples? 
What motivates you to monitor your immunosuppression?  

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For how long do you intend to monitor your immunosuppression?  
 
Is monitoring your immunosuppression consistent with your health goals? 
Emotion 
On the days you obtain samples are you able to enjoy your normal day-to-day activities? Is this 
different for home vs lab? 
Does obtaining samples to monitor your immunosuppression cause an emotional response such as 
stress, gratefulness, or anxiety? If so, what? Why?  
To what extent do your emotions help or hinder your ability or willingness to obtain samples to 
monitor your immunosuppression? Is there a difference between venipuncture and home monitoring? 
 
Nature of the 
behavior/intervention 
What would need to be different for you to routinely obtain home samples? 
What would be helpful to prompt you to obtain samples? (how is this different than the reminders you 
received?) 
 
How long do you think it would take you to be comfortable with obtaining samples at home? 
 
Would it be easier or harder to obtain samples at home versus the lab? 
 
What do think you is most valuable about obtaining samples at home? What about the reminders?