ABSTRACT
Detecting drug-related problems (DRPs) is important in pharmaceutical care in for better therapeutic outcomes. Clinical pharmacists-led comprehensive medication management plays a crucial role in the rational use of drugs by preventing, identifying, and resolving DRPs. In this review, we aimed to determine the effect of interventions on patient outcomes performed by clinical pharmacists in Turkey. A systematic literature search was performed on PubMed, Google Scholar, EMBASE, Cochrane Library, and Turkish databases (ULAKBIM, Dergipark). The main categories were “clinical pharmacist”, “intervention”, and “Turkey”. Two reviewers reviewed each article independently. Two independent reviewers screened all records and extracted data; disagreements were resolved through a consensus. Randomized controlled studies, pre- to post-intervention comparison studies, and cross-sectional studies including pharmacist-led interventions were included in the review. This review included 15 articles evaluating clinical pharmacist interventions. Ten studies (66.7%) focused on DRPs and pharmacist interventions to these problems, while the remaining 5 (33.3%) studies focused on patient education and adherence issues. Studies were conducted in oncology (33.3%), geriatrics (20.0%), chest diseases (13.3%), psychiatry (6.7%), cardiology (6.7%), and infectious diseases (6.7%) clinics. When results of studies are reviewed, most of the interventions were made at the prescriber level followed by the drug level and patient level. Problems were solved in 54.2-93.2% of DRPs, and adherence, patient knowledge, or skills were improved in most of the studies. Most of the studies were carried out within the scope of a postgraduate or doctorate thesis and yet various positive outcomes such as the prevention of side effects, increased quality of life, and decreased duration of hospital stay were observed with high positive rates of interventions, which indicate that other healthcare workers are ready to collaborate with the clinical pharmacists in Turkey.
INTRODUCTION
A drug-related problem (DRP) is defined as “an event or circumstance involving drug therapy that actually or potentially interferes with desired health outcomes”.1,2 Detecting DRPs is important in pharmaceutical care, as DRPs are related to treatment outcomes. To identify and resolve DRPs in terms of rational drug use, clinical pharmacist-led comprehensive medication management plays a crucial role.2,3
Clinical pharmacists beyond the many other duties primarily provide pharmaceutical care to improve treatment adherence and to decrease DRPs.4,5,6 The quality of care may be improved by pharmaceutical care services in many diseases like hypertension,7 asthma,8 hyperlipidemia,9 and diabetes.10 The first step in pharmaceutical care services is identifying patients’ pharmaceutical care needs and the second step is developing an individualized pharmaceutical care plan, with respect to the patient’s knowledge, attitudes, and motivation. The third step is evaluating the outcomes of the pharmaceutical care plan. Finally, the fourth and fifth steps consist of implementing the care plan and continuous monitoring, respectively.11
Clinical pharmacy services, including pharmaceutical care, has developed in the USA in the 1960s. It has changed over time in terms of concept and the variety of practices.12 It has been linked to proper prescribing, preventing or reducing DRPs, adverse drug events, quality of life (QoL), medication errors, and cost charged during the treatment.13,14,15,16,17,18 According to the International Pharmaceutical Federation consensus report in 2009, clinical pharmacy services given should be global, which was established in many developed countries19 including Turkey.20
Clinical pharmacy service is a relatively new and developing concept in Turkey.21 The first discussions started in 1986.22 It has been performing since 1991 and was started at Marmara University, which opened the first postgraduate education program. In 1994, clinical pharmacy course was a part of undergraduate education at Hacettepe University. In 1997, Ankara University established the interdisciplinary clinical pharmacy postgraduate education program. In 1998, to promote clinical pharmacy in Turkey, “The Society of Clinical Pharmacy, KED” was established. Since 2003, many continuing education programs were organized by both KED and the “Turkish Pharmacists’ Association Academy of Pharmacy” on clinical pharmacy and pharmaceutical care.21 In Turkey, the first Department of Clinical Pharmacy was established at Hacettepe University in 2013, and thereafter at Marmara University and Inonu University.23 Although clinical pharmacy was established as a subdivision at Marmara University many years ago (1995) and allowed to open a department throughout Turkey in 2013, it still operates as a subdivision under the pharmacology department in some universities due to a lack of academic staff. Furthermore, in 2014, with the approval of the Grand national assembly of Turkey, clinical pharmacy became a legal specialty supported by “Law on pharmacies and pharmacy”. According to this law, pharmacists may take a special exam once a year and based on the scores of this exam, and a limited number of them may start the 3-year postgraduate clinical pharmacy specialty education in selected universities.24
As mentioned above, as a member of the multidisciplinary and interdisciplinary team, the clinical pharmacist has a significant role in improving the treatment, patient outcomes, and QoL. The positive impact of clinical pharmacist-led interventions on patient outcomes in terms of reduced hospital visits and mortality was reported in other countries.25,26 Another impact of clinical pharmacists is on the pharmacoeconomic parameters. Studies show that there is proven evidence on the economic benefits of clinical pharmacy services via reducing the total healthcare costs in various health departments.13,14
It is important to show nation-wide results from a developing science to emphasize weak and strong sides and guide complete education. This review aimed to present the impact of interventions performed by clinical pharmacists in Turkey on patient outcomes and shows an inside view of what has been done since the implementation of the clinical pharmacy program in Turkey, and to lead further comprehensive studies.
A systematic literature search (up February 20, 2020) was performed according to PICOS formatting on PubMed, Google Scholar, EMBASE, Cochrane Library, Turkish databases (ULAKBIM, Dergipark) with the headings “clinical pharmacist”, “intervention”, and “Turkey” with “AND” and “OR” operators. Two reviewers (EK and BKC) reviewed each article independently. The search strategy of PubMed was as per the following: [“pharmacists” (MeSH Terms) OR “pharmacists”(All Fields)] OR [“clinical”(All Fields) AND “pharmacist”(All Fields)] OR “clinical pharmacist” (All Fields) AND [“Turkey”(MeSH Terms) OR “Turkey”(All Fields)].
The general principles recommended in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements were used. Two independent researchers screened records, further extracted data, and disagreements were resolved through a consensus. Extracted data and quality assessment variables were presented in tables with a narrative description. Randomized controlled studies, pre- to post-intervention comparison studies, and cross-sectional studies which included pharmacist-led interventions were included. Even though abstracts, letters, and case reports were also read and evaluated, articles with no full-text, conference reports, reviews, editorials, letters, or case reports were excluded. Articles referring to countries other than Turkey were excluded. First author’s name, publication year, study design, the type of clinical pharmacist-led interventions, patient age, patient outcomes, and the acceptance rate of interventions were evaluated. The first author (EK) extracted the data, and another review author (BKC) did the double-checking. If there was any conflict, another author (MS or KD) made the final decision.
To prevent bias in individual studies, every researcher extracted data other than their study. Data extraction was undertaken by one reviewer using a tailored data extraction framework, developed to explicit data extraction elements related directly to the review question for the qualitative studies. All of the extractions were checked by a second reviewer. No additional analyses were made to combine the data.
This review included 15 articles out of 94 publications evaluating clinical pharmacist interventions in Turkey (Figure 1). The oldest article included in this review was published in 2007 and the latest was published in 2020. The distribution of publishing years of the articles is given in Graphic 1. The majority of the articles were published in Science Citation Index-Expanded indexed journals that were ranked in the third quartile and fourth quartile. The characteristics of the journals in which the articles were published are listed in Table 1. The study design of two (13.3%) of the 13 articles included were retrospective, while the remaining 13 (86.7%) were prospective. Ten studies (86.7%) focused on DRPs and pharmacist interventions to these problems, while the remaining five (33.3%) studies focused on patient education and adherence issues. Different versions of the Pharmaceutical Care Network Europe (PCNE) DRPs classification system was used in seven (46.7%) of the studies. Different tools, such as Beers’ criteria, screening tool of older persons’ potentially inappropriate prescriptions criteria, screening tool to alert doctors to the right treatment criteria and National Cancer Institute common toxicology criteria for adverse effects version 4, were used in other studies.
Studies were conducted in oncology (n=5, 33.3%), geriatrics (n=3, 20.0%), chest disease (n=2, 13.3%), psychiatry (n=1, 6.7%), cardiology (n=1, 6.7%), infectious diseases (n=1, 6.7%), and in clinical and community pharmacy (n=2, 13.3%). The studies were conducted in the inpatient (n=6, 40.0%), outpatient (n=7, 46.7%), and community pharmacy (n=2, 13.3%) settings. The characteristics of the studies, patients, and interventions are listed as Table 2.
The duration of the studies was between 3 to 11 months, the number of patients in the studies were between 25 and 186, and the average age of the patients included in the studies was between 33 and 80 years.
When the study outcomes were reviewed, most of the interventions were made at the prescriber level, followed by drug level, and patient level. Problems were solved in a median of 86% (54.2-93.2%) of DRPs, and adherence, patient knowledge, or skills were improved in these studies (Table 2).
DISCUSSION
According to our perspective, ours is the first study that reviewed the studies in the field of clinical pharmacy in Turkey. Clinical pharmacy services in Turkey still have not entered routine practices. It is thought that it will become a routine practice by 2023.24 Most of the studies included in this review were carried out within the scope of a postgraduate thesis. Therefore, most of these studies focused on clinical pharmacy services that were offered for the first time to the clinicians or patients. Because clinical pharmacists are still not a routine member of the interdisciplinary team, these studies were unable to address all the identified pharmaceutical care needs, and for the same reason, the duration of studies was limited to few months.
The findings of decreased adverse drug effects, improved appropriate prescribing, shortened length of hospital stay (LoS), and reduced costs were reported in many other studies from outside of Turkey.13,18,42 The outcomes of the interventions were beneficial in terms of visualizing clinical pharmacy activities and better results in patients. Positive outcomes were observed, such as reduction or prevention of side effects, improvement in QoL, and reduction in LoS in the hospital with the high acceptance rates of interventions by the physicians, which indicate that despite the obstacles that faced in clinical pharmacy services, other healthcare professionals are ready to collaborate with the clinical pharmacists in Turkey.
In China, it was determined that appropriate prescribing and patient knowledge about medications was enhanced with the implementation of clinical pharmacy practices both in inpatient and outpatient settings.43 Rotta et al.44 overviewed 49 systematic reviews between 2000-2010 and found that clinical pharmacy practices were focused on certain chronic diseases like blood pressure and glucose control. Due to the variability of methods, interventions about medication adherence and prescription appropriateness caused inconclusive results.
Pehlivanli et al.45 reviewed 46 articles published between 2006 and 2016 on the role of the clinical pharmacist. They found that the studies were mostly related to cardiovascular diseases (13%), adverse drug events (11%), and infectious diseases (9%). The evaluated studies were generally prospective, observational, or interventional studies.45 In Turkey, there were also studies conducted within the scope of clinical pharmacy but without pharmacist intervention. Adverse effects and compliance with antidepressants in patients with major depression were evaluated by Sancar et al.46 Most commonly in 56 patients, side effects such as dizziness, dry mouth, increased sleep were observed, and 73.2% of the patients were found to have low compliance with the treatment. In addition to the routine service they receive from the outpatient clinic, it is concluded that educating and monitoring the side effects and compliance by the pharmacists will contribute to preventing possible DRPs.46 In another study, the appropriateness of drug treatment was evaluated, and requirements of pharmaceutical care were identified in geriatric patients. A low level of knowledge about drug usage was detected in patients, and they were not informed about the proper drug use.47 Okuyan et al.48 aimed to evaluate the knowledge and attitudes of type 2 diabetic patients regarding the use of a disposable insulin pen. As a result of this study, missing or improper usage of the disposable insulin pen was observed in hospitalized patients.48 The patient risk score was used by Aras et al.49 to evaluate the risk of febrile neutropenia (FN) and to assess granulocyte colony-stimulating factors use, and its side effects in an outpatient clinic. They found that inadequate or unnecessary treatments should be evaluated for the risk of FN in each chemotherapy cycle and that a routine risk assessment can also be implemented.49 Abunahlah et al.50 conducted a study in internal medicine wards to identify DRPs in a teaching and research hospital in Istanbul, Turkey. In this study, 163 DRPs were determined by using the PCNE classification V 7.0 in 100 patients that used a total of 808 drugs. According to their results, age, LoS in hospital, number of drugs, renal impairment, and inflammation correlated with the causes of DRPs, and age, number of drugs, LoS in hospital, renal dysfunction, liver failure, diagnosis, and comorbidities correlated with the number of DRPs.50
Another concern is appropriate measures for the effectiveness of pharmacists’ services. Hospitalization, mortality, or outpatient visits should be used for the evaluation of effectiveness endpoints; however, an extended duration of follow-up periods is needed to demonstrate a potential input for these endpoints. Thus, intermediate or surrogate indicators may be used to evaluate the short-term effects of interventions. Short-term evaluation methods of the included studies were also explained in this review.
The American College of Clinical Pharmacy (ACCP) defined that clinical pharmacists are a primary source of scientifically valid information and advice regarding the safe, appropriate, cost effective use of medications, and optimizing medication therapy with the background of pharmaceutical care. They routinely provide updated knowledge that contributes to improved health and QoL to patients and healthcare professionals.51 According to the definition by ACCP, clinical pharmacists in Turkey are also contributing to many research projects in the field of clinical pharmacy and in various other health-related fields. They provide immense knowledge to other healthcare professionals. Since these publications were outside the scope of this study, they were not discussed.
The main limitations of the studies reviewed in this were study setting (one hospital) and the study size (small groups).28,29,32,34 Other limitations were retrospective evaluations of pharmacist interventions29,38 and the absence of a control group for comparisons.28 Additional controlled and prospective studies are also in progress for publication due to ongoing thesis or projects in Turkey. A significant expansion in the number of publications is expected due to the increase in the number of both graduates and special program graduates who were trained in the field of clinical pharmacy in the recent years.
The limitations of this review were that even though a literature search was conducted on different databases, there might have been omitted or overlooked studies. PRISMA checklist items could not be fully followed because the studies included in this review were not homogeneous, and the available studies were few. Future studies are needed to assess the impact of clinical pharmacist interventions on health expenditure in Turkey by using cost-effectiveness or cost-benefit analysis methods.
CONCLUSION
In conclusion, there is a growing practice of clinical pharmacy in Turkey; however, a clear definition of clinical pharmacy services, implementation to the routine healthcare team, and standardized methods that assess the impact of these services on patient health-related outcomes are still needed. It is shown that even with the institutional effort, clinical pharmacy services may make a strong contribution to the Turkish healthcare system, but for providing a trustworthy and sustainable service, governmental and educational support should be developed.