Pills and Ills: Methodologic Issues in Pharmacologic Research
To The Editor: Medications are the most frequently used form of therapy employed in the care of older adults. Unfortunately, the frequent exclusion of these patients from premarketing clinical trials of new medications has limited our knowledge regarding the safety and efficacy of individual medications in our aging population.1 Moreover, the most common chronic condition that older adults experience is multimorbidity, with two of every three older adults having multiple chronic conditions. Multiple chronic conditions account for 66% of the country’s overall health expenditures and more than 95% of Medicare expenditures.2 Therefore, it is critical to understand the risks and benefits of medications in the presence of multimorbidity.
Despite this, a recent study showed that of 190 clinical trials that explicitly considered multiple chronic conditions in the selection process, 94% excluded older patients – i.e., the very patients who have the most to benefit from therapy and in whom we know the least about medication safety.3 Because of this gap, the role of observational data and pharmacoepidemiogic research in older adults is critical. In this letter, we summarize key points from a Methodology Workshop of the same title presented at the 2013 American Geriatrics Society Annual Scientific Meeting.
MEASURING MEDICATION ERRORS
As noted in the Institute of Medicine 2007 report, a medication error can be defined as “any error occurring in the medication-use process.”4 Two of the most important medication errors in older adults are potentially inappropriate medication use and medication non-adherence.
Potentially inappropriate medication use
Potentially inappropriate medication use can be measured by two approaches – implicit or explicit criteria. The most common implicit approach is using the Medication Appropriateness Index, which has been previously described.5 It has been shown to have good reliability and predictive validity with important outcomes, including adverse drug events ([ADEs] defined as injury due to a drug), in numerous studies.5
The other approach to measuring potentially inappropriate medication use is with explicit criteria. The most common explicit approach is using the Beers criteria in the US or STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions) criteria in Europe.6,7 Advantages of this approach include the fact that explicit criteria do not require a medical record review by a skilled practitioner, and they can be measured on large populations. The main disadvantage is that they require continuous updating based on new evidence. Future work is needed to further elucidate the association between these explicit criteria and important health outcomes in older adults.
Medication adherence
Medication adherence can be measured using a variety of methods. The two most common ways are via self-report and pharmacy claims. Self-reported methods of medication non-adherence offer advantages in that they are inexpensive, easy-to-administer, and capture actual patient medication-taking behavior and/or beliefs. The main potential disadvantage of self-reported methods is social desirability bias (i.e., some patients report what they think the prescriber wants to hear rather than their actual medication-taking behavior). For pharmacy claims-based adherence, researchers and health systems are able to measure and monitor adherence on large groups of patients (population-level estimates) using objective methods.8 However, pharmacy claims are inherently limited by the use of multiple pharmacies or health plans over time, the fact that medication-filling does not equal medication-taking, and the wide variety of definitions used in the literature.8 For example, different studies use various operational definitions for claims-based medication adherence, including the Medication Possession Ratio (MPR), the Proportion of Days Covered (PDC), and the Cumulative Medication Gap (CMG), among others. In addition, some studies assess primary non-adherence (i.e., when a drug is prescribed but the patient fails to pick up the prescription from the pharmacy) and medication persistence (i.e., the duration of time from initiation to discontinuation of therapy).9 Despite these limitations, pharmacy claims-based measures of medication adherence are becoming increasingly important in health policy initiatives, including the CMS 5-Star Ratings. In addition, the International Society of Pharmacoeconomics and Outcomes Research has published a checklist to be considered when conducting pharmacy claims-based adherence research.10 Future research is needed to examine more sophisticated approaches to understanding and measuring medication adherence to complex medication regimens. Taken together, potentially inappropriate medication use and medication non-adherence represent two of the highest priority areas in geriatric pharmacoepidemiological research.
CONCLUSION
Pharmacoepidemiologic research continues to have a vital role in advancing our understanding of the medication use process in older adults given their frequent exclusion from clinical trials. Potentially inappropriate medication use and medication adherence are two components of the medication use process needing the greatest attention from clinical and health policy perspectives.
ACKNOWLEDGEMENTS
SPONSOR’S ROLE
The sponsor of this research had no role or influence in matters relating to research design, methods, subject recruitment, data collection, analysis and/or preparation of the paper.
Funding sources: The authors received grant support from National Institute on Aging grants (R01 AG037451, R01 AG027017, P30AG024827, T32AG021885, K07AG033174, R21AG045320), National Institute of Nursing Research (R01NR003178), Agency for Healthcare Research and Quality (R18HS020831) and VA HSRD (IIR 12-379) grants.
Footnotes
Conflict of Interest Disclosures: None of the authors has relevant financial interests, activities, relationships, or affiliations, or other potential conflicts of interest to report.
| Elements of Financial/Personal Conflicts | Zachary Marcum | Jerry Gurwitz | Cathleen Colón - Emeric | Joseph Hanlon | ||||
|---|---|---|---|---|---|---|---|---|
| Yes | No | Yes | No | Yes | No | Yes | No | |
| Employment or Affiliation | X | X | X | X | ||||
| Grants/Funds | X | X | X | X | ||||
| Honoraria | X | X | X | X | ||||
| Speaker Forum | X | X | X | X | ||||
| Consultant | X | X | X | X | ||||
| Stocks | X | X | X | X | ||||
| Royalties | X | X | X | X | ||||
| Expert Testimony | X | X | X | X | ||||
| Board Member | X | X | X | X | ||||
| Patents | X | X | X | X | ||||
| Personal Relationship | X | X | X | X | ||||
AUTHOR CONTRIBUTIONS
Paper concept: Marcum, Gurwitz, Colón-Emeric, Hanlon.Drafting of the manuscript: Marcum, Gurwitz, Colón-Emeric, Hanlon.
Critical revision of the manuscript for important intellectual content: Marcum, Gurwitz, Colón-Emeric, Hanlon.
Obtained funding: N/A
.A symposium of the same title was presented at the American Geriatrics Society Annual Scientific Meeting on May 4, 2013.