Advertisement

Author's Reply

Open ArchivePublished:November 22, 2019DOI:https://doi.org/10.1016/j.jval.2019.09.2754
      We thank the editor for giving us the opportunity to respond to the letter to the editor regarding our recent publication on multiple medication adherence (MMA).
      • Pednekar P.
      • Ágh T.
      • Malmenäs M.
      • et al.
      Methods for measuring multiple medication adherence: a systematic review–report of the ISPOR medication adherence and persistence special interest group.
      We also thank the authors of the letter to the editor for their interest in our paper and for providing their comments, as it validates the timeliness and importance of this topic and offers the opportunity for an ardent discussion, which we believe is a hallmark of good science. At issue, in this case, is the measurement of adherence that involves polytherapeutic regimens. Although it is a methodologically challenging endeavor, subject to multiple dimensions and varied opinions, we believe that as more patients experience numerous medical comorbidities and hence polypharmacy needs, additional insights and novel approaches will be required to better document adherence measures. One of our intentions in documenting currently utilized MMA methods in our systematic review was to support future insights and novel approaches that we believe will ultimately support the viewpoint that ability of adherence to predict and stimulate action should be the focus.
      The letter from our respected colleagues raises four main issues. First, they assert that variations in MMA measures do not necessarily reflect "true” adherence. Although we firmly agree with this argument, we would like to highlight that our systematic literature review was aimed at identifying and characterizing the MMA methods currently being utilized by adherence researchers; we did not seek to identify the perfect method for measuring MMA.
      • Pednekar P.
      • Ágh T.
      • Malmenäs M.
      • et al.
      Methods for measuring multiple medication adherence: a systematic review–report of the ISPOR medication adherence and persistence special interest group.
      Nevertheless, documentation of the current methods provides a source for future studies to draw upon when determining the best measure of MMA for their situation and simultaneously considering methodological variations. In fact, different measures might be more appropriate for unique medical conditions or populations. In addition, regardless of the epistemological philosophy that one adopts, the truth is that patients experience an infinite array of perceived benefits and risks that factor into their medication behavior and the reasons behind that are beyond the scope of our systematic literature review on MMA measures.
      The second issue refers to an apparent lack of evidence that various definitions of MMA actually lead to meaningful difference in published results. Consequently, the reviewers suggested a random-effects model (REM) technique for a more rigorous meta-analysis. Indeed, REM is the preferred analytical technique to handle heterogeneity in meta-analyses. The goal of our study, however, was to inform different international healthcare stakeholders about the numerous measurement methods currently used by researchers to calculate MMA via a comprehensive systematic review and not to provide a single estimate for further analysis.
      • Pednekar P.
      • Ágh T.
      • Malmenäs M.
      • et al.
      Methods for measuring multiple medication adherence: a systematic review–report of the ISPOR medication adherence and persistence special interest group.
      Moreover, the studies included in our review were too diverse in terms of populations, outcomes, disease conditions, and so on. Statistical solutions used in meta-analysis would not have been appropriate.
      The third concern refers to a lack of detailed discussion on thresholds for nonadherence used in the studies included in our systematic literature review.
      • Pednekar P.
      • Ágh T.
      • Malmenäs M.
      • et al.
      Methods for measuring multiple medication adherence: a systematic review–report of the ISPOR medication adherence and persistence special interest group.
      There are a multitude of different adherence measures and none are considered the “gold standard,” with some methods overestimating adherence (such as simple days supplied summations) and others underestimating adherence (such as when early refills are not detected and shifted appropriately). Given that, it should not be surprising that, directionally, studies may have similar results regardless of the method, but consensus on thresholds is lacking. We agree that developing a consensus on MMA measure and defining the thresholds for MMA is a complex issue and needs further investigation. Raising awareness about the differences in MMA measures may be a key step in setting thresholds that consider the method as well as the other underlying complexities.
      In regard to the final concern raised by the reviewers, we would like to highlight that we do not think that proportion of days covered (PDC) completely avoids early refills.
      • Hui R.L.
      • Adams A.L.
      • Niu F.
      • et al.
      Predicting adherence and persistence with oral bisphosphonate therapy in an integrated health care delivery system.
      ,
      • Nau D.P.
      Proportion of days covered (PDC) as a preferred method of measuring medication adherence.
      The discussions in our review mainly focused on the finding that PDC is one of the most common measures used to calculate MMA and several variations of PDC were used. Still, strict adherence to a covered day methodology may not allow for shifting of coverage when refills are picked up early, and it was not always clear how this was handled. Such methodological details are important when assessing a measure’s likelihood of overestimating or underestimating adherence and therefore should be documented.
      Overall, the issues raised by the comments in the letter are insightful and further illustrate the daunting complexity of measuring and addressing medication adherence. Such ideas represent significant directions for future research into the myriad of concepts surrounding this topic. Nevertheless, we believe our work thoughtfully considered the rich current literature and incorporated key perspectives of the multitude of methods for calculating MMA. The insightful issues raised in the editorial review of our systematic literature review further illustrate the complexity of measuring and addressing medication adherence in an era of multiple comorbidities. To that end, we would like to extend a warm invitation to the reviewers to join the ISPOR Medication Adherence and Persistence Special Interest Group (MAP-SIG) to provide ongoing expertise and new perspectives as this area of research continues to unfold.

      References

        • Pednekar P.
        • Ágh T.
        • Malmenäs M.
        • et al.
        Methods for measuring multiple medication adherence: a systematic review–report of the ISPOR medication adherence and persistence special interest group.
        Value Health. 2019; 22: 139-156https://doi.org/10.1016/j.jval.2018.08.006
        • Hui R.L.
        • Adams A.L.
        • Niu F.
        • et al.
        Predicting adherence and persistence with oral bisphosphonate therapy in an integrated health care delivery system.
        J Manag Care Spec Pharm. 2017; 23: 503-512https://doi.org/10.18553/jmcp.2017.23.4.503
        • Nau D.P.
        Proportion of days covered (PDC) as a preferred method of measuring medication adherence.
        Pharmacy Quality Alliance, Springfield, VA2012