Analyzing Adherence to Prenatal Supplement: Does Pill Count Measure Up?

Abstract

Objective. To determine if adherence as measured by pill count would show a significant association with serum-based measures of adherence. Methods. Data were obtained from a prenatal vitamin D supplementation trial where subjects were stratified by race and randomized into three dosing groups: 400 (control), 2000, or 4000 IU vitamin D3/day. One measurement of adherence was obtained via pill counts remaining compared to a novel definition for adherence using serum 25-hydroxy-vitamin D (25-OH-D) levels (absolute change in 25(OH)D over the study period and the subject's steady-state variation in their 25(OH)D levels). A multivariate logistic regression model examined whether mean percent adherence by pill count was significantly associated with the adherence measure by serum metabolite levels. Results. Subjects' mean percentage of adherence by pill count was not a significant predictor of adherence by serum metabolite levels. This finding was robust across a series of sensitivity analyses. Conclusions. Based on our novel definition of adherence, pill count was not a reliable predictor of adherence to protocol, and calls into question how adherence is measured in clinical research. Our findings have implications regarding the determination of efficacy of medications under study and offer an alternative approach to measuring adherence of long half-life supplements/medications.

Comparison of methods to assess adherence to small‐quantity lipid‐based nutrient supplements (SQ‐LNS) and dispersible tablets among young Burkinabé children participating in a community‐based intervention trial

“…However, disappearance rate is also susceptible to manipulation (Appelgren et al . ). Because the disappearance rate and the daily reported adherence rate were high, and we suspect that the daily reported adherence rate was inflated, we believe that sharing may have occurred frequently in case of SQ‐LNS.…”

“…Disappearance rate calculated according to the number of returned product packages resulted in similar adherence estimates compared with daily reported adherence for both SQ-LNS and dispersible tablets. However, disappearance rate is also susceptible to manipulation (Appelgren et al 2010). Because the disappearance rate and the daily reported adherence rate were high, and we suspect that the daily reported adherence rate was inflated, we believe that sharing may have occurred frequently in case of SQ-LNS.…”

Early pregnancy vitamin D status and risk of preeclampsia

“…While the current evidence from randomized controlled trials (RCTs) is not sufficient to support 25OHD screening and high-dose vitamin D supplementation (>2,000 IU) in all pregnant women (39,40), screening and modification of vitamin D status in early pregnancy and ideally before pregnancy for women with a high risk of vitamin D deficiency should be considered. Furthermore, for to-be pregnant women with a high risk of vitamin D deficiency as well as a risk of nonadherence to vitamin D sup- The Journal of Clinical Investigation plementation, prepregnancy supplementation strategies such as a high dose of vitamin D 3 in addition to individualized supplementation doses should be considered, and frequent 25OHD measurements during pregnancy are recommended (41). These concepts need to be definitively tested in a prepregnancy clinical trial in a population of women at high risk of preeclampsia.…”

A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina

“…Adherence to the vitamin D supplementation regimen was measured by maternal self-report and pill counts at each follow-up visit (15). If a woman missed one prenatal visit, her next month’s supply of vitamins was mailed to her or delivered to her residence.…”