The Medication Appropriateness Index: A Clinimetric Measure

We read with interest the recent editorial by Dr. Fava celebrating the 40th anniversary of the introduction of “Clinimetrics” by Alvan Feinstein, MD [1]. We are celebrating the 30th anniversary of our clinimetrically derived tool for measuring potentially inappropriate prescribing (PIP), namely the Medication Appropriateness Index (MAI) [2]. We last reviewed the MAI on its 20th anniversary of the first publication [3]. We developed the MAI in the early 1990s for use as a sensitive measure of PIP in a randomized controlled trial of a clinical pharmacist intervention working with older outpatients with polypharmacy [4]. We were heavily guided by the writings of Dr. Feinstein in developing the MAI [5]. The MAI is an implicit measure widely used consisting of 10 criteria (Fig. 1; full instructions are available upon request from the first author). Ratings for “C” receive a weight ranging from 1 to 3 with a total maximum score per drug of 18 [3]. To the best of our knowledge, there are no other implicit measures of PIP with a widespread use. In contrast, there are multiple explicit measures, two of which are the AGS Beers criteria [6] and the STOPP (Screening Tool of Older Person’s Prescription) criteria [7]. These PIP explicit criteria, however, do not address the criterion of effectiveness, directions, therapeutic duplication, or cost. Below, we provide information about the reliability, validity, and responsiveness to change of the MAI and end with a discussion of novel applications of a modified MAI.

Fig. 1.

Medication Appropriateness Index.

/WebMaterial/ShowPic/1405379Reliability

There have been numerous reports regarding the good to excellent inter- and intra-rater reliability of the MAI. The most recent one comes from a before-after trial of a clinical pharmacist removal from an acute geriatric unit [8]. They found that the inter-rater reliability between two pharmacists was good (kappa statistic 0.82), as were their ratings compared to an expert pharmacist (kappa statistic 0.75). Another pilot study examined the inter- and intra-rater reliability of the MAI between two clinical pharmacologists and found good inter-rater reliability (intraclass correlation coefficient [ICC] 0.83–0.94) and excellent intra-rater reliability (ICC 0.90–0.99) [9]. These results are consistent with the previous reports of inter-rater reliability testing between a clinical pharmacist and a geriatrician, which was good (kappa statistic 0.92 and ICC 0.74) [2, 10].

Validity

A number of studies demonstrate the content and predictive validity of the MAI. The most recent studies confirmed content validity in comparison with explicit measures of PIP. One study determined the prevalence of PIPs according to Beers, STOPP, FORTA (Fit fOR The Aged), and MAI criteria, as well as the predictors for PIPs in geriatric outpatients taking a total of 2,645 medications [11]. PIPs were present in 53.1%, 55.7%, 44.3%, and 74% of patients according to Beers, STOPP, FORTA, and MAI criteria, respectively. Respondents taking ≥5 medications were found to be using significantly more PIPs according to Beers, STOPP, FORTA, and MAI criteria in comparison to those taking ≤4 medications. Another study estimated the prevalence of PIPs in 593 community-dwelling persons aged 65–74 years with multimorbidity and polypharmacy (total prescriptions = 4,386) according to Beers, STOPP, and MAI criteria in primary care [12]. PIP was detected in 57.7%, 68.8%, and 94% of patients according to the explicit criteria of STOPP, Beers, and MAI (at least one criterion positive), respectively. For every new drug taken by a patient, the MAI score increased by 2.41 points. Another study validated the Ghent Older People’s Prescriptions community Pharmacy Screening (GheOP3S) tool, an explicit screening method to detect PIP in 60 community pharmacy patients (≥70 years, ≥5 drugs chronically) admitted to the acute geriatric ward of a hospital. The completeness of PIP screening with the GheOP3S tool was evaluated through comparison with the adapted MAI. The adapted MAI detected 536 items, of which 145 were also detected by the GheOP3S tool. A total of 119 PIP items were additionally detected by the GheOP3S tool [13].

Two recent studies added to the literature on the predictive validity of the MAI. Investigators validated a risk score, the “80+ score,” for revisits to hospital and mortality for older patients and compared the discriminatory ability of the score with STOPP, START, and MAI using C-statistics in 368 patients, aged 80 years and older, admitted to two acute internal medicine wards [14]. The C-statistics showed similar discriminatory abilities, i.e., 0.71 (80+ score), 0.57 (STOPP), 0.54 (START), and 0.63 (MAI), demonstrating that all measures had an association with rehospitalization or death. In another study that aimed to internally validate prognostic models to predict health-related quality of life as measured by the EQ-5D-5L, investigators used data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomized controlled trial (n = 502, ≥60 years, ≥5 drugs, ≥3 chronic diseases) and examined multiple variables in mixed regression models [15]. They found that the MAI score was a significant predictor of health-related quality of life. The above studies are consistent with previous reports of MAI content and predictive validity [2, 3]. In particular, previous predictive validity studies showed that higher MAI scores were significantly associated with unscheduled ambulatory or Emergency Department visits and inadequate blood pressure control, adverse drug events using a modified MAI score, and adverse drug reactions by drug-disease interaction criteria [3].

Responsiveness to Change in Clinical Trials

There were nine randomized controlled trials published from 2012 to the present [9, 16-23] (Table 1). Most focused on older adults in outpatient clinics. None were conducted in long-term care facilities. The most common intervention involved a pharmacist (6 of 9 studies). The improvement in MAI scores was statistically significant in 7 of 9 studies. This contrasts with the findings from our original study in which the MAI score at 12 months was 28% lower in the intervention group compared to only 5% in the control group [4]. It is important to note that there remains a challenge in defining a relevant change in MAI scores despite the MAI demonstrating predictive validity with important patient outcomes [24].

Table 1.

Randomized controlled trials to improve MAI scores in adults

/WebMaterial/ShowPic/1405381New Applications of the MAI

A recent trend is to use a modified MAI consisting of fewer items than the original 10 to measure PIP for specific drug classes. For example, Hanlon et al. [25] used an abbreviated MAI consisting of items for antibiotic effectiveness, dosage, drug-drug interactions, and duration for older nursing home patients with suspected cystitis. Previously, our group published several papers examining unnecessary drug use using 3 MAI items: indication, effectiveness, and therapeutic duplication (Fig. 2) [26-28].

Fig. 2.

Unnecessary drug use as per specific MAI items.

/WebMaterial/ShowPic/1405377

The full MAI has also been used to study therapeutic futility specifically at the time of transition to the palliative care setting [29]. Finally, Tesfaye et al. [30] used the MAI to study PIP in older hospitalized adults with chronic kidney disease. These studies show the utility of the MAI in different forms and settings beyond the original use in older veteran primary care patients.

Conclusions

As described above, the clinimetrically derived MAI has been shown to be reliable and valid, and it is widely used to measure PIP in a variety of adults from a variety of clinical settings. An obstacle to its use, though, is the persisting issue that it takes 10 min per drug to apply the MAI [2]. The study by Hanlon et al. [25] and studies by others [26-28] addressed this time concern by using fewer individually reliable items from the MAI. The future seems bright for the MAI as study protocols from at least three randomized controlled trials note their intention to use the MAI as an outcome measure [31-33]. In conclusion, we believe that the MAI is now timelier than ever, because of the problems of medication overload and polypharmacy in older adults and the MAI’s relationship with adverse health outcomes including iatrogenic effects.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding from research was used to prepare this manuscript.

Author Contributions

Each author wrote sections of the manuscript, edited and approved a final version.

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