Even your pill bottle spies on you.

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Tuesday January 10th at 9 pm Eastern

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Automated Reminders and Physician Notification to Promote Immunosuppression Adherence Among Kidney Transplant Recipients: A Randomized Trial

Reese PPBloom RDTrofe-Clark JMussell ALeidy DLevsky SZhu JYang LWang WTroxel AFeldman HIVolpp K.

Am J Kidney Dis. 2016 Dec 7.
PMID: 27940063

Update: Free Full text available (till Jan 17th) at this link, thanks to AJKD


As a pediatric nephrologist, I have a little experience with nonadherence. We know that our adolescent kidney transplant recipients have the highest risk of graft loss between 18 and 21 years of age, no matter how old they were when they got their kidney, predominantly due to non-adherence.

Even though we can see it coming a mile away, we haven’t figured out how to improve adherence in this age group. And it’s not that we haven’t tried. Researchers have studied just about everything in an attempt to improve adherence with various success including electronic weekly drug dispensing devices, online educational modules, and personal coaching and adherence support teams. Therefore, it was with great interest that I read this week’s #NephJC article studying a new approach to promoting adherence. Will this method finally be the answer to my adherence nightmares?


This was a single center randomized controlled trial of adult kidney and kidney-pancreas transplant recipients at the University of Pennsylvania. 120 patients were enrolled within the first 2 weeks of transplant and received an electronic pill bottle for their tacrolimus.

Patients were randomized into one of three arms and followed for 6 months:

Arm 1: Adherence monitoring with customized reminders. The electronic pill bottle would chime and a light would flash when medication was due. In addition, participants could select to have text, phone, or email reminders sent as well.

Arm 2: Same as arm 1 PLUS provider notification. When adherence dipped below 90% over 2 weeks, the coordinator would be notified and they would contact the patient, discuss issues, and document a note that was sent to the remainder of the transplant team.

Arm 3: Pill bottle only without flashing and beeping reminders

The primary outcome was adherence defined as pill bottle openings, calculated for the final 90 days of the intervention period as percentage of days with bottle openings as expected.


Participants were predominantly male (60%), white (54%), and primary transplant recipient (88%).

In the control arm (Arm 3), adherence was 55% compared to 78% in the customized reminders group (Arm 1) and 88% in the customized reminders plus notification group (Arm 2). This was a statistically significant 24% and 33% higher adherence, respectively, with the interventions. Nice!

There were no differences between groups in tacrolimus levels, tacrolimus coefficient of variation, or in the fraction of tacrolimus levels in the target range. All of these are markers of nonadherence that have been correlated with the hard outcomes of rejection, donor specific antibody formation, and graft loss in prior studies (Table 2). The reasons for the disconnect between tacrolimus monitoring and adherence as defined by pill bottle opening were unclear.

Interestingly, in an end of study survey, nearly all participants self-rated their adherence close to 100%. Hmmm……Sounds familiar.


Finding strategies to improve adherence and prolong graft survival is a noble goal and the authors should be applauded for their initiative and use of readily accessible technology to improve transplant patient health. There are several limitations, however. They recognize that their study measures pill bottle opening only and not pill ingestion. If my pill bottle was flashing and beeping at me, I might just open and close it to shut it up for a while, fully intending to go back and (probably) take it later (as anyone who’s silenced a beeping IV pole fully intending to go tell the nurse later can attest to, sometimes you forget despite good intentions). Even short term outcomes such as acute rejection episodes would have been a welcome addition to the adherence outcomes reported. An additional study limitation was that the coordinators were not blinded to the intervention. This has significant potential to bias results given the close contact between coordinator and transplant patient in the first 6 months after transplant. Finally, cost was not discussed. While devices and wireless technology are getting cheaper by the day and invading our medical lives they can add a lot to the cost of medical care over the course of ~17,000 transplants per year in the US. If we’re going to fully adapt these, we’ll need to be sure that they help us achieve the outcomes we’re hoping for: longer graft life, fewer rejection episodes, and happier healthier transplant recipients. I look forward to a follow up study from this group.

Summary by Michelle Rheault, MD
Medical Director of Dialysis
Associate Professor of Pediatrics