Efficacy of a Pharmacist Team Clinical Medication Review in Older Adults: A Prospective and Retrospective Observational Study

Abstract

Polypharmacy in older adults causes problems such as increased adverse drug reactions, overdose or duplication, and poor medication adherence. We have established a “medication review team” organized by pharmacists. This prospective and retrospective observational study evaluated the effectiveness of the pharmacist-led team-based approach for reducing polypharmacy as compared to the individual pharmacist approach. Data on the individual pharmacist approach were collected retrospectively, but prospectively for the pharmacist-led team approach. The study included patients who were admitted to the nephrology, orthopedic surgery, and psychiatry wards. Characteristics for patient included in each study group were adjusted using the propensity score method. The pharmacist-led team approach had a significantly higher medication change rate compared to that of the individual pharmacist approach (odds ratio (OR), 2.28; 95% confidence interval (CI), 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with discontinuation of potentially inappropriate medications was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). Our results suggest that it is possible to improve the quality of medication review by conducting team conferences even with only pharmacists.

INTRODUCTION

Polypharmacy is defined as the problems related to excessive medication use, such as adverse drug reactions (ADRs), overdose, duplication, or poor medication adherence. Older adults have especially enhanced drug responses due to pharmacokinetic shifts caused by age-associated decreased physiological function.¹⁾ In addition, they have multiple chronic comorbidities with an increased load of medications²⁾; and drug–drug interactions are, thus, a concern.³⁾ A systematic review and meta-analysis reported that the frequency of ADRs in older patients was 22% and that the main predictors are medication-related factors, including polypharmacy.⁴⁾ A Japanese observational study also showed that polypharmacy was associated with the occurrences of ADRs⁵⁾ as well as falls.⁶⁾ Polypharmacy was also shown to be associated with increased dosing frequency, which reduces medication adherence.^7,8) Despite these problems, the frequency of older adults using at least five medications has been reported to be 35.8% and has increased over the past five years.⁹⁾ Furthermore, 48.4% of homebound older adults use at least one potentially inappropriate medication (PIMs).¹⁰⁾ Therefore, correction of polypharmacy has been recognized as an important clinical issue.

Identification and assessment of PIMs by pharmacists has been shown to be useful in correcting polypharmacy.^11–13) Moreover, clinical medication review, not as a “prescriptions only review,” but a “comprehensive clinical evaluation for disease management,” is considered to be important.¹⁴⁾ To conduct the ideal medication review, many obstacles, including personnel shortage for extracting patients who need medication review, insufficient interprofessional collaboration, and difficulty in assessing polypharmacy in the context of clinical conditions, need to be surmounted. Although each clinical pharmacist had approached the problem individually, as is common practice in our hospital, the quality of intervention was highly uneven because of the barriers mentioned prior. To improve the quality and the consistency of interventions, we established a “medication review team” organized by pharmacists with different levels of expertise in June 2021. Collaboration between clinical pharmacists and this team was expected to improve the quality of approach to polypharmacy. This study was aimed at evaluating the effectiveness of clinical medication review by a pharmacist-led team.

MATERIALS AND METHODS

Pharmacists-Led Team Approach for Polypharmacy

The “Medication Review Team” consisted of pharmacists in charge of the nephrology, orthopedic surgery, and psychiatry wards. The team evaluated whether duplicate medications and drugs with the risks of ADRs should be discontinued, and assessed the benefits of continuing each medication from the clinical symptoms. Based on the results of the clinical medication review, the clinical pharmacists shared the information with the nurse, confirmed the wishes of the patient and family, and discussed their findings with the physician. Flow of the pharmacists-led team approach for polypharmacy is shown in Fig. 1.

Fig. 1. Flow of the Pharmacists-Led Team Approach for Polypharmacy

Study Design

This was a prospective and retrospective observational study based on the medical records of patients at Fujita Health University Hospital. The observation period of this study was six months both in the usual (individual pharmacist approach) as well as the pharmacist-led team approach. The individual pharmacist approach time period examined was from July to December 2020; the pharmacist-led team approach phase took place between July and December 2021. Data were collected retrospectively during individual pharmacist approach prior to the establishment of the medication review team, and prospectively during the pharmacist-led team approach after the establishment of the medication review team.

The study included patients admitted to the nephrology, orthopedic surgery, and psychiatry wards within each observation period. The inclusion criteria were as follows: 1) age ≥65 years, 2) number of oral medications ≥6, and 3) hospital stay ≥14 d. In the prospective observation, the hospital stay was not determined at the time of medication review. Instead, we screened patients by estimating the hospital stay and excluded those with less than 14 hospital days at the time of analysis. Patients were excluded if they were transferred to the palliative care wards, or if they died. This study was approved by the Institutional Review Board of Fujita Health University (HM21-095).

Assessments

The primary outcome in the comparison between the individual pharmacist and the pharmacist-led team approach was the rate of patients with medication change. This was calculated as the number of patients with medication change divided by the number of matched cases. This outcome was aggregated only for cases in which the medication was changed as a result of discussion by the clinical pharmacists with physicians and other interprofessional dialogue. The secondary outcomes examined in each of the two groups were the rate of patients with two or more medication discontinuation, the rate of patients with PIMs discontinuation, and the rate of patients with interventions suggested by young clinical pharmacists. PIMs were detected based on the “List of drugs to be prescribed with special caution” in the Screening Tool for Older Persons’ Appropriate Prescriptions for Japanese (STOPP-J).¹⁵⁾ Young clinical pharmacists were defined as pharmacists with three years or less of clinical experience in hospital wards. As the other outcomes, we compared the effectiveness of pre- and post-the pharmacist-led team approach, the changes in the number of medications and PIMs, and drug costs in patients who changed any medications between admission and discharge. Drug costs were converted to United States Dollar (USD, $) at a conversion rate of 114.83 Japanese Yen (JPY) to $1 (as on 1/Mar/2022). We also classified the discontinued medications based on the Anatomical Therapeutic Chemical (ATC) classification.

Statistical Analysis

We used propensity score matching to adjust for confounding factors between the individual pharmacist approach and the pharmacist-led team approach groups. Propensity scores were estimated by a logistic regression model including the following seven covariates: age, sex, weight, body-mass index (BMI), clinical department, number of medications, and fall risks. Matching was performed with the nearest-neighbor matching algorithm without replacement using a caliper width equal to 0.2 of the standard deviation of the logit of the propensity score. We considered covariates with a standardized mean difference (SMD) of less than 10% to be adequately balanced in the comparison between the individual pharmacist approach and the pharmacist-led team approach groups.

For comparisons between the individual pharmacist approach and the pharmacist-led team approach groups, odds ratio (OR) and 95% confidence interval (CI) were calculated using Fisher’s exact test. The endpoints pre- and post-the pharmacist-led team approach were obtained using paired t-test. p-Values were two-sided and those less than 0.05 were considered to be significant. The sample size was set as the number of feasible cases during the observation period. All statistical analyses were conducted using R 4.1.2 (The R Foundation for Statistical Computing).

RESULTS

Patient Characteristics

Based on quantitative screening criteria, 616 patients were extracted in each observation period (individual pharmacist approach, 301 patients; pharmacist-led team approach, 315 patients). A total of 6 patients were excluded in the individual pharmacist approach period (transfer to palliative care wards, 2 patients; death, 4 patients) and 295 patients were analyzed. A total of 10 patients were excluded in the pharmacist-led team approach period (transfer to palliative care wards, 5 patients; death, 5 patients) and 305 patients were analyzed. Before propensity score matching, each group had different proportions of patients in various departments as well as different fall risks. A total of 272 patients in each group were matched by propensity score matching (Fig. 2). The SMDs for all covariates were less than 10%, and the covariate balance in the matched data was well adjusted. The patient characteristics at baseline are summarized in Table 1.

Fig. 2. Patient Flow throughout the Study

Table 1. Patient Characteristics

	All cases before propensity score matching			Matched cases after propensity score matching
	Individual pharmacist approach (n = 295)	Pharmacist-led team approach (n = 305)	SMD	Individual pharmacist approach (n = 272)	Pharmacist-led team approach (n = 272)	SMD
	n (%)	n (%)		n (%)	n (%)
Age (year), mean ± S.D.	77.4 ± 6.7	77.8 ± 7.0	0.054	77.5 ± 6.7	77.4 ± 6.8	0.026
Male sex (%)	131 (44.4)	138 (45.2)	0.017	124 (45.6)	119 (43.8)	0.037
Weight (kg), mean ± S.D.	53.7 ± 11.1	54.5 ± 11.0	0.065	54.3 ± 10.8	53.9 ± 10.8	0.034
BMI (kg/m2), mean ± S.D.	22.2 ± 4.3	22.5 ± 4.0	0.072	22.5 ± 4.2	22.4 ± 4.0	0.011
Departments
Nephrology (%)	81 (27.5)	76 (24.9)	0.13	72 (26.5)	71 (26.1)	0.018
Orthopedic surgery (%)	186 (63.1)	209 (68.5)		181 (66.5)	183 (67.3)
Psychiatry (%)	28 (9.5)	20 (6.6)		19 (7.0)	18 (6.6)
Number of medications, mean ± S.D.	9.7 ± 3.2	9.8 ± 3.1	0.034	9.8 ± 3.2	9.7 ± 3.1	0.032
High risk of falling (%)	149 (50.5)	137 (44.9)	0.11	130 (47.8)	126 (46.3)	0.029

Abbreviations: S.D., standard deviation; SMD, standardized mean difference; BMI, body-mass index.

Comparison of the Individual Pharmacist and the Pharmacist-Led Team Approaches

The results of the difference between the individual pharmacist and the pharmacist-led team approach groups are shown in Fig. 3. The pharmacist-led team approach group had a significantly increased rate of patients with medication change compared to that of the individual pharmacist approach group (OR, 2.28; 95% CI, 1.21 to 4.46; p = 0.009). The rate of patients with two or more medication discontinuations and the rate of patients with intervention by young clinical pharmacist were also significantly higher in the pharmacist-led team approach group (OR, 2.19; 95% CI, 1.06 to 4.74; p = 0.03 and OR, 5.67; 95% CI, 1.22 to 53.15; p = 0.02, respectively). The rate of patients with PIM discontinuation was not significantly different between the two groups (OR, 2.07; 95% CI, 0.86 to 5.33; p = 0.11). The same pharmacists were involved in this study between the individual pharmacist and the pharmacist-led team approaches.

Fig. 3. Comparison of the Individual Pharmacist Approach and the Pharmacist-Led Team Approach

Comparison Pre- and Post-pharmacist-led Team Approach

Of the 305 patients who met the quantitative screening criteria, 130 patients were selected through qualitative screening criteria and clinical medication review was conducted in the team conference. The rate of patients with medication change was 29.2% (38/130 patients). The rates of patients with two or more medication and PIM discontinuations were 20.8% (27/130 patients) and 15.4% (20/130 patients), respectively. The rate of patients with intervention by young clinical pharmacist was 9.2% (12/130 patients). The results of pre- and post-the pharmacist-led team approach are shown in Table 2. The pharmacist-led team approach significantly reduced the number of medications (t (37) = 7.57, p < 0.001) and PIMs (t (37) = 4.97, p < 0.001). The drug costs were significantly reduced after the pharmacist-led team approach. (t (37) = 2.60, p = 0.01). A total of 125 medications were discontinued through the pharmacist-led team approach, 28 medications of which were PIMs. The ATC classification of medications that were discontinued (at least three or more) is shown in Table 3. The ATC classification of most discontinued medications was psycholeptic (8.0%, 10/125 patients). Analgesics, antigout preparations, and diuretics were the next most frequently discontinued medications (all 6.4%, 8/130 patients).

Table 2. Comparison of Pre- and Post-pharmacist-led Team Approach

	Patients (n = 38)		t	df	P
	Pre-approach	Post-approach
Number of medications, mean ± S.D.	10.3 ± 3.8	8.0 ± 3.2	7.57	37	< 0.001
Number of PIMs, mean ± S.D.	2.6 ± 1.3	2.0 ± 1.3	4.97	37	< 0.001
Drug costs (USD, $), mean ± S.D.	9.90 ± 7.23	7.75 ± 5.65	2.60	37	0.01

Abbreviations: S.D., standard deviation; PIM, potentially inappropriate medications; USD, United States Dollar.

Table 3. ATC Classification of Discontinued Medications

ATC classification	Medications (n = 125)
	n (%)
Psycholeptics	10 (8.0)
Analgesics	8 (6.4)
Antigout preparations	8 (6.4)
Diuretics	8 (6.4)
Drugs for acid related disorders	7 (5.6)
Blood substitutes and perfusion solutions	6 (4.8)
Calcium channel blockers	6 (4.8)
Agents acting on the renin–angiotensin system	5 (4.0)
Topical products for joint and muscular pain	5 (4.0)
All other therapeutic products	4 (3.2)
Drugs for constipation	4 (3.2)
Antiepileptics	3 (2.4)
Antihistamines for systemic use	3 (2.4)
Antineoplastic agents	3 (2.4)
Cough and cold preparations	3 (2.4)
Drugs for functional gastrointestinal disorders	3 (2.4)
Psychoanaleptics	3 (2.4)

Abbreviations: ATC, Anatomical Therapeutic Chemical.

DISCUSSION

The present study evaluated the effectiveness of pharmacist-led team approach for polypharmacy. Pharmacist-led team approach was shown to be superior to the individual pharmacist approach in terms of changing and discontinuing medications, as well as promoting intervention by young clinical pharmacists. As a result, this approach resulted in a reduction in the number of medications, PIMs, and drug costs. Previous studies have reported that pharmacist interventions have reduced the number of medications,^16–18) reduced the ADRs,¹⁹⁾ and improved patient QOL.²⁰⁾ Our results support the utility of pharmacist intervention for polypharmacy. The roles of pharmacists in these studies are primarily medication review, detection of PIMs, and assessment of ADRs and drug–drug interactions. The detailed tasks varied between studies and were largely performed by the pharmacists, either alone or as part of multidisciplinary geriatrics teams. Although the multidisciplinary geriatric teams, which include physicians, might be useful for improvement of polypharmacy, young pharmacists cannot play an initiative role because of lack of their specialty. Our results suggest that pharmacist-led teams support young pharmacists in honing their expertise and providing intervention suggestions in the clinical approach to polypharmacy.

The approach also significantly reduced the number of PIMs, but showed no advantage over the individual pharmacist approach, and PIMs accounted for only 20% of discontinued medications. These results may be due to the limited approach of a pharmacist-only medication review team. Intervention by pharmacists as part of a multidisciplinary geriatric team is generally considered to provide greater benefits than intervention by pharmacists alone.²¹⁾ In addition, reducing polypharmacy in patients with multiple comorbidities has been shown to be more effective when collaborating with specialists such as cardiologists and neurologists.²²⁾ To correct polypharmacy more widely, it is necessary to constitute a multidisciplinary polypharmacy team in collaboration with physicians, nurses, and other professionals.

Although our approach significantly reduced drug costs, it is difficult to evaluate the health economic utility with only this result. For example, the implementation costs, such as human resources (e.g. pharmacists, physicians and nurses), need to be considered. This study was a naturalistic observational design and costs incurred not be accurately assessed because the personnel involved were not uniform in the case of each patient. A cost-benefit study in Spain has reported that reduced drug costs exceeded labor costs for the intervention.²³⁾ Conversely, Laberge et al. have pointed out that only a few studies have conducted a sufficiently systematic economic evaluation, and almost all of them displayed low-quality cost-effectiveness results because of omitting intervention costs (medical fee, labor costs, etc.), as is the case in the results pertaining to cost-and-benefit in the current study.²⁴⁾ In addition, intervention costs differ among countries, and further evidence is needed for results to be generalized.

A major limitation of our study is that the methods of data collection differ between the individual pharmacist and the pharmacist-led team approach groups (retrospective and prospective). We applied three quantitative criteria (age, number of medications, and hospital stay) to unify the population for each approach, and further adjusted for patient background using the propensity score method. However, the patient populations approached in each group may have been fundamentally different. In addition, we did not evaluate the skill development of existing pharmacists, therefore the association of individual pharmacist skill development with our results is unclear. Another limitation is that it is difficult to assess whether the additional medications are related to the pharmacist-led team approach. Although a pharmacist-led team suggested to discontinue medications, there were few suggestions of additional medications for the treatment of the primary disease during the observation period. Moreover, only outcomes related to drug change were assessed; outcomes relating to clinical outcomes were not. Although clinical medication review is effective in reducing PIMs, it may not necessarily lead to improved clinical outcomes.²⁵⁾ According to the Cochrane review, the impact of Medication Reviews on death and rehospitalization is not clear.²⁶⁾ Therefore, future approaches should consider clinical outcomes, not only during hospitalization, but also after discharge.

Our study revealed that the pharmacist-led team approach was more effective in correcting polypharmacy in the older adults than the individual pharmacist approach. Although it is obvious that a multidisciplinary team approach is preferable, it seems possible to improve the quality of medication review by conducting pharmacist-led team conferences. Further studies should examine the direct clinical benefit of this type of intervention on polypharmacy; additionally, since polypharmacy is not only an inpatient issue, interventions geared towards the outpatient setting, in collaboration with family physicians, home-visiting pharmacists, and nurses, should be considered.

Acknowledgments

This work was supported by the Promotion project for the appropriate medication for Elderly Patients by the Ministry of Health, Labour and Welfare.

Conflict of Interest

The authors declare no conflict of interest.

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