Encouraging Mail Order Pharmacy Use to Improve Outcomes and Reduce Disparities
Phase: NA
Conditions: Diabetes Mellitus
Sponsor: Kaiser Permanente

Encouraging Mail Order Pharmacy Use to Improve Outcomes and Reduce Disparities 
NCT02621476 
Document date: 10/1/2020 

Encouraging Mail Order Pharmacy Use to Improve Outcomes and Reduce Disparities 
CLINICAL TRIAL PROTOCOL 
Abbreviations: 
CVD: 
cardiovascular disease 
HPHC: Harvard Pilgrim Health Care Institute 
IVR: 
automated telephone call (interactive voice response) 
KP: 
Kaiser Permanente 
KPNC: Kaiser Permanente Northern California 
KPHI: 
Kaiser Permanente Center for Health Research, Hawaii 
LDL:      Low-density lipoprotein 
PDC:     Proportion of Days Covered 
 
OBJECTIVE: 
In this study, we seek to determine whether targeted, patient-centered interventions to encourage mail 
order pharmacy use will result in greater rates of mail order pharmacy use as well as improvements in 
medication adherence. We conducted a randomized encouragement trial to encourage use of the 
existing mail order pharmacy among diabetes patients with poor adherence to CVD risk factor 
medications who use only retail pharmacies and examined whether the intervention’s impact differs 
across key subgroups.  The specific aims of this clinical trial are to: 
 
Aim 1: To test whether outreach strategies to encourage mail order pharmacy use will increase rates of 
mail order pharmacy use (Primary Outcome) in diabetes patients at high risk for poor health outcomes. 
Aim 2:  To examine whether encouraging the use of mail order pharmacy services to deliver 
cardiometabolic medications results in greater medication adherence, and to assess differences in the 
impact of the intervention across key subgroups. 
 
BACKGROUND: 
There is an urgent need for effective, sustainable interventions to improve diabetes medication 
adherence. Good medication adherence is associated with improved control of CVD risk factors, fewer 
hospitalizations, and lower mortality in patients with diabetes mellitus. However, only about 50-70% of 
patients with chronic conditions such as diabetes are adherent to their regular medications. In response 
to this problem, literally hundreds of interventions to improve adherence have been evaluated and 
published over the last 60 years. Traditional interventions almost always require substantial investments 
of personnel, time, and/or financial resources. However, they generally show only modest 
improvements in adherence, which dissipate completely once the active intervention phase concludes. 
Recent approaches such as medication therapy management are expensive to implement and limited to 
small subgroups of patients (e.g., Medicare Part D enrollees with multiple chronic diseases and multiple 
medications). These types of resource-intensive interventions will be challenging to disseminate and 
implement more widely and are unlikely to reach large numbers of adults with diabetes. Disparities in 
medication adherence are prevalent among patients with diabetes. The underlying reasons for these 
disparities in adherence are multifactorial, and include inability to afford prescribed medications, low 
health literacy and low health numeracy, low patient self-efficacy, inadequate patient-provider 
communication, and difficulty accessing pharmacies. Since poor medication adherence is linked to poor 
diabetes outcomes, improving adherence among minority and low-SES patients is critical in any effort to 
improve health care outcomes for these populations. There is only limited evidence that broadly 
targeted quality improvement efforts such as diabetes registries and care reminders impact disparities 
in diabetes care.  

Evidence is growing that voluntary mail-order pharmacy use is linked to better adherence and 
outcomes. While the majority of efforts to improve adherence are focused on changing behavior at the 
individual level, recent studies have examined the role of pharmacy choice as a determinant of 
adherence. One recent multi- level analysis found that the between-pharmacy variation in medication 
adherence was significant and represents an independent pharmacy-level effect on adherence not 
explained by individual-level factors. This study also found that voluntary use of a mail-order pharmacy 
as compared to a retail pharmacy was associated with an 8-percentage point improvement in adherence 
to antidiabetic medications. Investigators on our study team have replicated this finding in several 
analyses using observational data for different chronic conditions, employing statistical approaches to 
mitigate selection bias. These studies show not only improved medication adherence with mail-order 
pharmacy use, but also lower LDL cholesterol among statin users and a decrease in racial disparities in 
adherence to antihypertensive medications. There is an urgent need for a well-designed, randomized 
trial to test strategies for improving mail order pharmacy use in diabetes patient at risk for poor health 
outcomes.  
STUDY SETTING: 
Research activities took place at the (3) locations listed below. 
1. 
Kaiser Permanente Northern California (KPNC), Division of Research, Oakland, California 
2. 
Kaiser Permanente Center for Health Research (KPHI), Honolulu, Hawaii  
3. 
Harvard Pilgrim Health Care (HPHC) Institute, Boston, Massachusetts   
 
STUDY DESIGN: 
This study conducted a randomized encouragement trial to encourage use of the existing mail order 
pharmacy among diabetes patients with poor adherence to CVD risk factor medications who use only 
retail pharmacies. Subjects were randomized to (2) arms: 1) the intervention arm and 2) the usual care 
arm.  Those randomized to the intervention arm, at all sites, received encouragement to use mail order 
pharmacy services by receiving an outreach letter, which includes information about the benefits of mail 
order pharmacy use, and information on how to enroll in mail order pharmacy services at their 
individual site.  In addition, those randomized to the encouragement at KPNC and KPHI received an 
encouragement outreach email (secure message) and a pre-recorded phone message.  Since phone and 
email contact with patients is not standard of care with HPHC, they received letter-only encouragement 
outreach. There was no outreach follow-up.  Observational EHR data was used to examine the impact of 
the intervention on mail order use and medication adherence. Those patients randomized to the usual 
care arm did not receive any form of encouragement outreach from the study team. 
STUDY POPULATION: 
a.  NUMBER OF SUBJECTS 
63,012 total participants 
 
b.  INCLUSION AND EXCLUSION CRITERIA 
Inclusion Criteria: 
• 
Age 18 years or older 
• 
Have a diagnosis of diabetes as indicated by EHR 
• 
Have active health plan membership in the past 12 months  
• 
Non-adherent (PDC <80%) to at least one oral CVD risk factor medications in the past 12 months  
• 
Have no evidence of mail order pharmacy use to refill oral CVD risk factor medications.  
 
 
 

Exclusion Criteria: 
• 
Pregnancy or Dementia/Traumatic Brain Injury diagnosis in the past 12 months 
• 
Hospitalized, in Skilled Nursing Facility, Hospice, or Home Health at the time of randomization 
 
 
WAIVER OF INFORMED CONSENT and HIPPA PRIVACY RULE AUTHORIZATION: 
A waiver of informed consent and HIPPA Privacy Rule Authorization was granted from KPNC IRB (IRB of 
record for this study) for participants in the study intervention.  The only known risk is disclosure of 
confidential information. Safeguards were be put in place to prevent the loss of privacy and to prevent 
breaches of confidentiality. This study represented no more than minimal risk participants. 
 
STUDY PROCEDURES:  
Eligible patients were randomized into (2) arms: 1) an intervention arm and 2) a usual care arm.  Those 
randomized to the intervention arm, at all sites, received encouragement to use existing mail order 
pharmacy services by receiving an outreach letter, which includes information about the benefits of mail 
order pharmacy use, and information on how to enroll in mail order pharmacy services at their 
individual site. The instructions on how to enroll in the existing mail order pharmacy services came 
directly from health plan operations materials. In addition, those randomized to the encouragement 
arm at KPNC and KPHI also received an encouragement outreach email (secure message) and pre-
recorded phone message.  Since phone and email contact with patients is not standard of care with 
HPHC, they received letter-only encouragement outreach.  The letter and email outreach will be 
delivered only once.  The Interactive Voice Response (IVR) system was programmed to make up to the 
IRB approved maximum attempts to contact eligible participants via phone to play the approved pre-
recorded message:  If a call is answered, the message begins.  No PHI was disclosed in the outbound 
message.  At the end of the call patients were given the opportunity to be transferred to their local mail 
order pharmacy phone line.   Eligible members can hang up at any time and were not re-dialed.  Those 
patients randomized to the usual care arm did not receive any outreach from the study team. 
 
DATA ANALYSIS: 
To examine the relationship of encouraging MOP use with MOP use and adherence, we estimated the 
differences in MOP use and CVD medication adherence at follow-up between the two arms using Chi-
square tests in an intent-to-treat (ITT) analysis. Differences in the percentages of CVD drug fills delivered 
by mail were estimated using T-Test. To determine whether MOP use differed by race/ethnicity we 
calculated risk ratios using modified Poisson regression comparing the effect of treatment on outcomes 
within each group.  We used Chi-square tests to compare the percent of patients with a hospitalization 
or emergency department visit during follow-up between the intervention and control arm and 
compared the number of primary care visits between arms using the Kruskal-Wallis test. Patients who 
died or who disenrolled from their health plan during follow-up were excluded from the analysis. In 
addition, those who did not have a CVD medication fill during the follow-up period were also excluded 
since we were unable to assess whether they used MOP. Sensitivity analysis was conducted to assess 
the impact of those without CVD medication fills during follow-up by including them in the analytic 
population as non-users of MOP at follow-up. All analyses were further stratified by site and results from 
both the KP sites were collapsed based on the similarity of study results in the two sites, and because 
their pharmacy distribution structure and health care systems were also similar in comparison to HPHC.