The Pill Bottle Study: The Patient Perspective

Once again NephJC is proud to have Kevin Fowler present his views on our NephJC discussion.

The topic of adherence is a nice follow on to the FDA Patient Focused Drug Development meeting on September 27, 2016. The meeting was for “Patients Who Have Had an Organ Transplant."  At this meeting half the agenda was dedicated to adherence in transplant recipients.  I am encouraged by the recent increased attention to adherence in kidney transplant recipients. 

After reviewing the AJKD article, “Automated Reminders and Physician Notification to Promote Immunosuppression Adherence Among Kidney Transplant Recipients: A Randomized Trial”, I was not surprised with the results of the primary and secondary endpoint:

Mean adherence was 78%, 88%, and 55% in the reminders, reminders-plus-notification, and control arms (P , 0.001 for comparison of each intervention to control). Mean tacrolimus levels were not significantly different between groups.

Allow me to explain my reasoning.

For the primary outcome, adherence to tacrolimus was measured by pill bottle openings during the final 90 days of a 6 month study. The use of electronic reminders and provider notifications resulted in a mean adherence of 88% compared to 78% for reminders alone.  It appears that the majority of provider notifications were done by transplant coordinators.

After I had my kidney transplant, my transplant coordinator was instrumental to my success.  She was very empathetic, compassionate, and understanding of my emotional ups and downs.  When I was facing the uncertainty of whether my body would accept my kidney, my coordinator was always available, and I always felt comfortable sharing my concerns.  Thus, if a transplant coordinator were to be notified of a possible missed dose, this creates an opportunity for a patient engagement conversation.  More times than not, I would expect the coordinator to uncover why the patient missed the dose, and then provide effective patient coaching.

In the secondary outcome there were no significant differences across arms in scheduled tacrolimus levels, tacrolimus coefficient of variation or percent of tacrolimus levels in the target range.  I was not surprised for a couple reasons.

First, nephrologists have very limited and antiquated diagnostic tools to measure tacrolimus dosing and post- transplant kidney function.  While tacrolimus levels have provided some value in dosing, they do not provide the  level of specificity that a companion test offers.  Moreover, this study underscores the combined prognostic limitation of tacrolimus drug levels and serum creatinine test.

Second, there have been numerous case reports and anecodotal reporting of kidney transplant recipients who have lived several decades post-transplant without consistent medication adherence. While this behavior is not encouraged, it reflects how much is unknown about immunology, and the need for new post-transplant tests.

While the results of this study are encouraging, the results of this study should be seen for what they are, reminder alerts and provider notifications are effective patient engagement tactics, not a strategy.                                           

The first step in developing a patient engagement strategy is understanding the patients.  Transplant recipients are not a monolithic group,. For example, in my 12+ years post-transplant, I have never used once a reminder system.  After witnessing what my Mom and Aunt experienced on dialysis, my fear of dialysis serves as a powerful motivator to remain healthy.  Literature results show that PKD transplant recipients like myself have better transplant outcomes compared to the rest of the transplant population.  I think a major contributing factor is that we have seen relatives on dialysis, and are particularly motivated to succeed.

We now live in the age of “Big Data”, and this provides the transplant communityan opportunity to gain deep patient insights.  I recommend that the transplant community prioritize their collective efforts at understanding the emotional fears, needs, desires, etc of transplant recipients.  While some members of the community are doing this,, a coordinated and collaborative approach would not only improve understanding of adherence but could serve as the foundation for developing novel patient engagement strategies.

Through my professional pharma patient marketing experience, I have learned that patient engagement strategies are frequently developed without first investing in patient insights.  An investment in “Big Data” would be the first step and most important step in developing patient engagement strategies.

Once the date is consolidated and analyzed, I would anticipate that the profiles of 4-5 transplant recipients would be developed.  These profiles would provide insights into the type of communication and support patients desire.  Currently, patient communication is done with a one size fits in all.  The patient insights would enable more personalized approaches and thus be more effective.