key: cord-0077378-8qcjo6v3
authors: Ahmed, Ali; Dujaili, Juman Abdulelah; Hashmi, Furqan Khurshid; Awaisu, Ahmed; Chaiyakunapruk, Nathorn; Hasan, Syed Shahzad
title: The economic impact of pharmacist care for people living with HIV/AIDS: A systematic review
date: 2021-08-30
journal: Explor Res Clin Soc Pharm
DOI: 10.1016/j.rcsop.2021.100066
sha: bd3f222c78a0e50eaf62374b6b73338f4cd87929
doc_id: 77378
cord_uid: 8qcjo6v3

BACKGROUND AND OBJECTIVE: There is an increase in the global prevalence of the human immunodeficiency virus (HIV). While it has been proven that pharmacist interventions improve the health outcomes of people living with HIV/AIDS (PLWHA), the economic impact of these initiatives is uncertain. Consequently, we aim to systematically review and synthesize the evidence surrounding the economic impact of pharmacist care in PLWHA. METHODS: PubMed, EMBASE, Scopus, IPA via ProQuest, the Cochrane Library, and the CINAHL Plus databases were systematically searched. Original studies evaluating the economic effect of pharmacist-managed services for PLWHA were included in the review. The quality of the economic studies was assessed using the Consolidated Health Economic Evaluation Reporting Standard (CHEERS) checklist. RESULTS: A search of databases yielded 4206 citations, four of which met the eligibility criteria. Three studies were conducted in a hospital-based outpatient facility, while one study was conducted in a community pharmacy setting. The types of “pharmacist-managed services” included targeted motivational education, pharmaceutical care, health screening for opportunistic infections, and referral to specialists. Two of the four economic evaluation studies had complete economic analyses and were rated as moderate in quality. In comparison with usual care, pharmacist services led to cost savings of (51.29 to 165.74 in 2021 USD$) per person per year, saving 18.5 h per patient per year, and a lower cost of generating 12 years of quality-adjusted life years. In addition, the benefit-to-cost ratio of the pharmacist service was 2.51:1. CONCLUSIONS: The pharmacist-managed services demonstrated the benefits of improving overall PLWHA health outcomes in economic viability. However, future real world controlled, high-quality economic studies are required to determine the long-term cost-effectiveness of these services, given the pharmacist's growing role in the health care team managing PLWHA.

As of 2020, approximately 37.7 million people globally are living with the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). 1 Of these, more than 50% are from low-and middleincome countries (LMICs). 2 The socioeconomic burden of HIV/AIDS is notable because of the significant strain and cost incurred on people living with HIV/AIDS (PLWHA), their relatives, and the community. 3 Between 2000 and 2015, $562.6 billion was spent on HIV/AIDS, and, in 2015 alone, $48.9 billion was spent on HIV/AIDS prevention, care, and treatment worldwide. 4 Furthermore, between 2000 and 2016, HIV/AIDS prevention investment increased by 519.6%, from $596 million to $3 billion. 5 On the other hand, AIDS-related deaths have decreased by 39% since 2010, owing primarily to the introduction of highly active antiretroviral therapy (HAART) in the early 2000s.. 1 The end of the AIDS threat by 2030 and the achievement of UNAIDS 95-95-95 targets will largely depend on the effectiveness of the current antiretroviral therapy (ART), which will contribute to viral suppression, reduction in the spread of the virus, and prevention of AIDS-related deaths. [6] [7] [8] ART plays a crucial role in HIV prevention and management, 9, 10 and pharmacists play an invaluable role in maintaining the continuity and safety of their use. 11, 12 Pharmacists offer high-quality, patient-oriented medication therapy management services for PLWHA. 13, 14 Pharmacist interventions could mitigate medication errors, improve medication literacy skills and adherence. 15, 16 With pharmacist care, PLWHA could control their condition and better health outcomes. 14, 17 Consequently, the use of healthcare facilities and resources, such as clinic and emergency room admissions, could be decreased, thereby lowering increased health spending. 16, 18 A meta-analysis conducted by Ahmed et al. in 2021 (including evidence from inception to June 2020) showed that the availability of pharmaceutical services to PLWHA was correlated with statistically meaningful increases in adherence to medication and had a beneficial influence on viral suppression. 12 Other studies have also reported pharmacists' positive effects on patients' CD4 T lymphocyte counts, viral loads, and ART adherence. 11, 15, 19, 20 The American Society of Health-System Pharmacists (ASHP) now considers pharmacy services an essential component of HIV care. 12, 21, 22 However, previous systematic reviews evaluating pharmacist interventions did not focus on economic consequences or directly targeted PLWHA health outcomes. 11, 12, 23 As a result, we plan to conduct a systematic review of the literature to assess the economic outcomes of pharmacist care for PLWHA.

We registered the systematic review on PROSPERO (CRD42020173057) and followed the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines for reporting the findings. 24 

The studies were included if they were: (1) original research publication; (2) analysing pharmacist-managed services in PLWHA; (3) document an economic assessment; (4) written in English; and (5) available in full text. However, workshop materials published guidelines, case reports, editorials, opinions, letters to editors, commentaries, correspondences, news articles, qualitative studies and conference abstracts were excluded if not available in full-text form.

The following electronic databases were searched: PubMed, EMBASE, Scopus, international pharmaceutical abstracts (IPA) via ProQuest, the Cochrane Library, and the CINAHL Plus. Three categories of keywords, i.e., pharmacist managed services (e.g., 'pharmacists'), HIV (e.g., 'AIDS'), and economic assessment ('economics') describing the key components of the research question, were used with variations from inception to 23 February 2021. Both free-text keywords and headings unique to the databases were used (e.g., MESH and EMTREE) (Supplementary Table S1 ).

Bibliographies of relevant documents were searched manually to identify any additional records that were not found from the electronic searches. Two authors independently screened the titles and abstracts of all the documents listed. The full-text of potentially eligible titles/abstracts was retrieved for a full review by two independent reviewers. Any discrepancies between the two reviewers were resolved through discussion and consensus. A third independent reviewer was consulted when an agreement was not reached.

Information extracted from the included studies includes author(s), study objectives, study design, comparison type, research setting, the country of study, inclusion and exclusion criteria, study duration, sample size, intervention (i.e., pharmacist services), control group(s), perspective(s), cost year, program costs, economic outcomes, significant statistical results, benefit-to-cost ratio, currency, and type of economic assessment. The comparison styles included pre-post, and inter-group comparisons. Control groups were categorized as parallel control for cross-group comparisons and historical self-control for pre-post comparisons. Study settings were classified as hospital-based outpatients or community pharmacies. The research perspectives were categorized as the patient, provider, or societal. 25 Finally, equivalents were provided for all currency values in 2021 USD, considering inflation and currency changes for each study. 26 In the current systematic review, program costs include the costs of implementing and sustaining pharmacy-managed project or programs (e.g., pharmacist salary time, incentives, office supplies, equipment's, facility space, and utility costs). On the other hand, economic outcomes include costs incurred with or without services (e.g., medication costs), cost reductions, per-case costs saved, and others. For example, the benefits-to-cost ratio, i.e., economic benefits per dollar spent on pharmacist-managed services, was established where appropriate, dividing service economic benefits by delivery cost for the same period. Furthermore, if the cost year was not explicitly stated in the research, the year of study completion was used.

The type of economic assessment was classified as suggested by Drummond et al. 25 based on the number of alternatives and whether the costs and intervention outcomes were analysed. Specifically, studies with two or more options (e.g., intervention group versus control group or historical control group) were considered as 'analysis' whereas those without control group were 'description.' A partial economic assessment may include a cost description, a cost analysis, a description of the outcome and an evaluation of the outcome. The full economic evaluation includes all cost and outcomes components, and studies can be further classified as costeffectiveness, cost-benefit, and cost-utility analysis. The quality evaluation of the economic studies was carried out using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 24-item checklist. 27 

We found 4204 articles in database searches and two articles in bibliographic searches. After removing duplicate articles remaining 3409 were screened for titles and abstracts. Finally, 48 articles were identified for the full-text review; 44 articles were excluded for the reasons listed in Fig. 1 , and four papers were included for the qualitative assessment. Table 1 summarises the characteristics of the included studies. A study was conducted in the USA, Mexico, Spain, and Brazil. 15, [28] [29] [30] Three studies were conducted in a hospital-based outpatient facility, 15, 28, 29 while one study was conducted in a community pharmacy setting. 30 In addition, three studies were prospective, single group, pre-post trials, 15, 29, 30 while the one study was a prospective, parallel controlled study. 28 The minimum sample size was 28, and the maximum sample size was 279. Two studies have a sample size of less than 50, 10, 19 while two studies have greater than 100. 28, 30 The duration of the two studies was six months, 15, 29 while the rest were conducted over 12 months. 28, 30 The pharmacist managed interventions utilized in the studies can be divided into five types: targeted education for adherence (n = 4) 15,28-30 ; pharmaceutical care (e.g., medicine review, modification, and recommendations for other health care providers) (n = 4) 15,28-30 ; health screening and laboratory services (n = 2) 15,30 ; referral to specialists (n = 2) 15,30 ; motivational interviewing for adherence (n = 1). 15 Table 2 summarises the economic characteristics and other outcomes of the included studies. Two studies reported partial economic assessments, i.e., outcome and cost description, 15, 29 while two studies measured the full economic evaluation, i.e., cost-benefit 28 and cost-effectiveness analysis. 30 One study was carried out from a provider perspective, 28 one from a patient perspective, 29 one from a societal perspective, 15 and one from both provider and societal perspective. 30 The program's costs include labor costs, and other costs, i.e., office (light, space rent), pharmacist training, and sustaining costs of pharmacist-managed services. 15 3 .38, 6.90, 1.38 in 2021 US $ of would be required for each additional outcome of viral load <50 copies/ml, absence of co-infection, CD4+ >200, 350, and 500 cells/mm3, and optimal immune response, respectively. The intervention group generated annual savings of US$ 32.33 per patient, i.e., 51.29 in 2021 US$ per year i.e., associated with appointments, laboratory tests, and hospitalizations. In addition, the intervention group reported a benefit-to-cost ratio of 2.51:1 compared to standard care. 28 According to Dilworth • Patients aged 18 years who were on or planning to start ART and who met the eligibility criteria (e.g., agreed to follow-up clinic and pharmacy visits, were willing to use project pharmacies to fill prescriptions, had an unmet immunological or virologic goal, failed a previous ART regimen) were enrolled in the project. • Three of the 10 project sites (Albany, GA, Chicago, IL, Kansas City, MO), which reported complete cost data, were included in the cost and cost-effectiveness analyses.

• Pharmacists with training on HIV treatment and prevention, stigma, and cultural competency, offered individualized adherence support. • Did initial comprehensive medication therapy review and subsequent quarterly targeted or comprehensive reviews depending upon the clinical need. • Monitored prescription patterns and tracked clinical and laboratory test results to assess treatment response and to identify potential therapy-related adverse events. The project pharmacists worked directly with their partnered clinics to develop action plans to address any identified therapy-related problems. • Plans were formulated in person (eg, "morning huddle" face-to-face meetings between the pharmacists and clinic providers) or by phone, fax, or email. Medical providers, pharmacists, and patients then collaborated to implement the action plans, and progress was reviewed at subsequent project visits. 30 In addition, studies have shown that pharmacist interventions have increased pharmacist intervention costs and reduced future medical costs (e.g., laboratory tests, appointments, hospitalization, and emergency visits costs), compensating for the increased cost of drugs.

Based on the CHEERS checklist (Table 3 ), all the four economic evaluations have fulfilled item 1 as the titles suggest that the studies have been an economic evaluation. All reviews have completed point 2, except for Carnevale et al., which was completed partially because the study perspective was not summarised. 28 No discounts were applied in all the studies because the duration of the studies was not more than one year. In item 19 of the CHEERS checklist, Dilworth et al. and Margusino et al. did not report any incremental analysis and consequences of alternatives. 15, 29 Modelbased structural uncertainties and input parameter delays were fully explained by Carnevale et al. and partially explained by Shrestha et al.. 28, 30 Carnevale et al. partially reported the differences in baseline subgroup differences and variability in intervention effects. 28 

This systemic review described and examined studies investigating the economic impact of pharmacist-managed services for PLWHA. Although pharmacist interventions have become more expensive as programme costs have risen, the overall impact of these interventions on improving PLWHA is far more significant, either directly or indirectly, than the cost of the intervention itself. Interventions had a positive impact on adherence to ART, viral load suppression, immune system improvement, avoiding opportunistic infections, laboratory costs, hospitalization, emergency hospital visits in intervention groups. Further, these interventions were also meaningful in reducing the HIV transmission to HIV-negative partners and improving QALYs. This result could have been linked to improved HIV management through improved drug monitoring, contributing to a general decrease in overall healthcare costs. Studies show that pharmacistmanaged programs resulted in cost-saving, demonstrating pharmacists' important role in HIV/AIDS management.

Pharmacists' role in healthcare has expanded from drug dispensing and distribution to individualized patient-cantered care, such as pharmacotherapy supervision and personalized education. [31] [32] [33] [34] The presence of pharmacists as a member of the HIV/AIDS healthcare management teams is likely to be sustained and gradually extended, especially following the recommendations of the World Health Organization (WHO) and the ASHP, each of which promotes the integration of pharmacists into a multidisciplinary team to improve PLWHA health outcomes. 6, 22 This review included one study conducted in a community pharmacy setting and three studies conducted in hospital outpatient settings. This was consistent with the related reviews of the pharmacist-managed services for diabetes and hypertension, which recognized that the pharmacist had increased pharmacotherapy services in outpatient settings. 18, 31 One theory may be that pharmacists are readily available and willing to provide prompt guidance on medications in outpatient settings, particularly for people who are on outpatient treatment for chronic diseases such as HIV/AIDS. The results in these studies will enable pharmacist managers to justify the budgetary benefit of pharmacist-managed programs and expand such services in ambulatory conditions, given the increasing recognition of pharmacists' contribution to the optimal use of medicine in chronic diseases. The results from studies conducted in the USA, Mexico, Spain, and Brazil cannot begeneralized to other countries due to variations in pharmacist skills and services performed.

There are a few limitations to mention. First, half of the included studies were full economic studies similar to a review conducted in an economic evaluation of pharmacist services in patients living with diabetes. 31 To encourage decision-makers to optimise the allocation of limited healthcare resources, full economic evaluations should be conducted and reported based on defined parameters, considering both cost and outcomes. Secondly, most research is from a provider's perspective, although only one study took a patient's perspective. In comparison, none of the studies found whether participants were insured because non-insured individuals appear to have low wages. Non-insured patients have fewer prescribed drugs and doctor's office visits but more emergency room visits, suggesting inadequate HIV treatment contributing to a substantial economic burden. Thus, potential research could be undertaken to examine the economic effect of pharmacist initiatives on such a perspective of uninsured individuals.

Third, two studies have investigated indirect costs, which account for a significant portion of the overall cost of HIV treatment. 15, 29 Bam et al. reported that cumulative total days missed in a monthly cycle due to HIV/ AIDS were 3.5 days lost. 35 As pharmacist-managed programs may increase individuals' health outcomes and productivity, the existing literature may not have entirely grasped these services' economic effects. Fourth, the uncertainty underlying the key point calculations and the cost and outcome expectations must be considered so differences in parameter values may not lead to different results and conclusions. Potential economic estimates of pharmacist interventions may employ one-way, multi-way, and probabilistic sensitivity testing and non-parametric bootstrapping to calculate discrepancies in estimates. Finally, establishing a causal link between pharmacist-managed services and their economic effects could use a study approach by using a concurrent control group and introducing randomization to reduce bias. Policymakers can find more solid and impelling evidence from future, randomized, controlled, large sample-sized trials.

There are some limitations associated with the present study. First, though a systematic search technique has been used to find qualifying studies, not all papers matching the inclusion requirements have likely been included. Secondly, this research is prejudiced by publication bias, and only certain reports that have been published could reflect the findings, and non-significant results may not have been published. Thirdly, no attempt was made to contact the authors of the studies examined to request information not reported; consequently, reporting bias could have been present. Finally, we did not include conference abstracts or dissertations that were not available in full text, so there may have been publication bias.

In conclusion, there was a good return in economic viability on programs run by pharmacists managed services in PLWHA. The evolving roles of pharmacists in HIV care and increases in medication costs promote the measurement of the economic effects of pharmacist initiatives. To assess the long-term cost-effectiveness of pharmacist services in HIV care, high-quality real-world observational, economic studies will be required in the future. 167, 168, 169 3, 5 e50, e51 19. For each intervention, report mean values for the main categories of estimated costs and outcomes of interest, as well as mean differences between the comparator groups. If applicable, report incremental cost-effectiveness ratios. 4, 5, 7 168, 169 c 5 c e50, e51 20a. Single study-based economic evaluation: describe the effects of sampling uncertainty for the estimated incremental cost and incremental effectiveness parameters, together with the impact of methodological assumptions (such as discount rate, study perspective). NA 168 NA NA 20b. Model-based economic evaluation: Describe the effects on the results of uncertainty for all input parameters, and uncertainty related to the structure of the model and assumptions. 4 NA NA e52 d 21. If applicable, report differences in costs, outcomes, or cost-effectiveness that can be explained by variations between subgroups of patients with different baseline characteristics or other observed variability in effects that are not reducible by more information 4, 5, 7 NA NA NA 22. Summarize key study findings and describe how they support the conclusions reached. Discuss limitations and the generalizability of the findings and how the findings fit with current knowledge. 5, 7, 8 169, 170 5, 6, 7 e51, e52, e53 23. Describe how the study was funded and the role of the funder in the identification, design, conduct, and reporting of the analysis. Describe other non-monetary sources of support. 8 171 7 E49 24. Describe any potential for conflict of interest of study contributors in accordance with journal policy. In the absence of a journal policy, we recommend authors comply with International Committee of Medical Journal Editors recommendations. 8 171 7 e53

Cost analysis of pharmaceutical care provided to HIV-infected patients: An ambispective controlled study. DARU

Clinical and economic effects of a pharmacist-administered antiretroviral therapy adherence clinic for patients living with HIV

Teleconsultation for the Pharmaceutical Care of HIV Outpatients in Receipt of Home Antiretrovirals Delivery: Clinical, Economic, and Patient-Perceived Quality Analysis

): p. e48-e54. ⁎ Page numbers listed, N/A; not applied. a Perspective not stated. b Study duration was not greater than 12 months. c An incremental analysis of costs and consequences of alternatives was not performed

UNAIDS. Global HIV & AIDS statistics 2020 fact sheet. AIDS-related deaths 2020

HIV/AIDS Key facts

I saw it as a second chance": a qualitative exploration of experiences of treatment failure and regimen change among people living with HIV on second-and third-line antiretroviral therapy in Kenya, Malawi and Mozambique

Spending on health and HIV/AIDS: domestic health spending and development assistance in 188 countries

Potential for additional government spending on HIV/AIDS in 137 low-income and middle-income countries: an economic modelling study

Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: recommendations for a public health approach. World Health Organization

Health-related quality of life and its predictors among adults living with HIV/AIDS and receiving antiretroviral therapy in Pakistan

Concerns of HIV-positive migrant workers in COVID-19 pandemic: A call for action

Four decades of HIV/AIDS-much accomplished, much to do

Translation and cross-cultural adaptation of WHOQOL-HIV Bref among people living with HIV/AIDS in Pakistan

The impact of HIV clinical pharmacists on HIV treatment outcomes: a systematic review

Effect of pharmacist care on clinical outcomes among people living with HIV/AIDS: a systematic review and meta-analysis

A pharmacist-led program to evaluate and reduce polypharmacy and potentially inappropriate prescribing in older HIV-positive patients

The effect of an integrated health system specialty pharmacy on HIV antiretroviral therapy adherence, viral suppression, and CD4 count in an outpatient infectious disease clinic

Clinical and economic effects of a pharmacist-administered antiretroviral therapy adherence clinic for patients living with HIV

Fundamentals of HIV MedicineCME

Mindfulness-based interventions for adults living with HIV/AIDS: a systematic review and meta-analysis

Economic evaluations of clinical pharmacy services

The pharmacist's expanding role in HIV pre-exposure prophylaxis

Impact of an HIV-trained clinical pharmacist intervention on error rates of antiretroviral and opportunistic infection medications in the inpatient setting

Role of the pharmacist in reducing healthcare costs: current insights

ASHP guidelines on pharmacist involvement in HIV care

Pharmaceutical interventions in antiretroviral therapy: systematic review and meta-analysis of randomized clinical trials

Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement

Methods for the economic evaluation of health care programmes

Adjusting for inflation and currency changes within health economic studies

Consolidated health economic evaluation reporting standards (CHEERS)-explanation and elaboration: a report of the ISPOR health economic evaluation publication guidelines good reporting practices task force

Cost analysis of pharmaceutical care provided to HIV-infected patients: an ambispective controlled study

Teleconsultation for the pharmaceutical care of HIV outpatients in receipt of home antiretrovirals delivery: clinical, economic, and patientperceived quality analysis

Costs and cost-effectiveness of the patient-centered HIV care model: a collaboration between community-based pharmacists and primary medical providers

Economic evaluations of pharmacist-managed services in people with diabetes mellitus: a systematic review

Bridging the gap for clinical pharmacist in developing countries like Pakistan

The Role of the Pharmacist in Patient Care: Achieving High Quality, Cost-Effective and Accessible Healthcare through a Team-Based, Patient-Centered Approach

The Effect of Pharmacist Services on Patient Health Outcomes in a Low Middle-Income Country: A Systematic Review

Strengthening adherence to anti retroviral therapy (ART) monitoring and support: operation research to identify barriers and facilitators in Nepal

We received no funding for this project.

Not required.

None.

Supplementary data to this article can be found online at https://doi. org/10.1016/j.rcsop.2021.100066.