Clinical pharmacists’ contributions to hematopoietic stem cell transplantation: A systematic review

Abstract

Aims

The goal of the present review was to identify studies that assess how pharmaceutical services contribute to hematopoietic stem cell transplantation (HSCT).

Methods

We conducted a systematic literature review of published studies describing results from clinical services provided by pharmacists working with HSCT, conducted according to PRISMA guidelines (PROSPERO registration number CRD42017062391). A search strategy was applied within PubMed, CENTRAL, EMBASE, SCOPUS, and LILACS databases in April 2017. Inclusion criteria were observational or experimental studies that addressed the following research question: “What are a clinical pharmacist’s main contributions to HSCT?” The quality of selected studies was evaluated using the Downs and Black checklist.

Results

We identified 1838 studies, and seven were included in the systematic review. The results indicated that clinical pharmacy is useful during HSCT treatment within both inpatient and outpatient settings. Pharmaceutical contributions identified included management of pharmacotherapy-related problems, participation in discussions with clinical teams, drug reconciliation, patient and team education regarding pharmacotherapy, preparation of guidelines and educational materials, and evaluation of medication adherence. These activities favored the control and prevention of pharmacotherapy-related problems, the maintenance of immunosuppressive serum levels, improvement in patients’ clinical and nutritional status, facilitated medication adherence, and provided economic and humanistic gains.

Conclusions

Despite the small number of articles discussing the topic under analysis, the results were unanimous in confirming the positive impact of pharmacists’ contributions to clinical practice for HSCT.

Keywords

Clinical pharmacy service hematopoietic stem cell transplantation bone marrow transplantation review

Introduction

Hematopoietic stem cell transplantation (HSCT) is a treatment that has been increasingly used in oncology and hematology. However, HSCT is an expensive therapeutic modality, associated with substantial rates of morbidity, mortality, and involves a highly complex pharmacological treatment, which is critical for success.^1–5 HSCT is mostly preceded by intense conditioning regimens and, in allogeneic HSCT, it is succeeded by multiple immunosuppressive strategies for preventing graft-versus-host disease (GVHD). Over a long period, patients require a wide range of supportive care to avoid or manage complications related to transplantation such as antiemetics, analgesics, corticosteroids, antifungals, antivirals, antibacterials, antiepileptics, and antihypertensives.^5–9 Some of these drugs have a narrow therapeutic range, interact with other substances, and are affected by genetic, physiological, and/or behavioral factors.^5,7,9

It is commonly necessary to prescribe off-label drugs for HSCT patients. In other words, drugs are used in disagreement with recommendations from the product registration of a regulatory agency, mainly regarding clinical indication, age, route of administration, dose, interval between doses, or formulation. Especially in pediatric HSCT, many of the drugs are used in an off-label way. Indeed, this may change pharmacokinetics and/or pharmacodynamics, increasing the risk of adverse events or reducing effectiveness.⁷ In addition, data on drug safety and efficacy should not be considered the same for adults and children, as drug handling and response can be different in this population.⁷

Due to complex pharmacotherapeutic regimens, patients undergoing HSCT are at high risk for developing pharmacotherapy-related problems (PRPs). Thus, the clinical pharmacist’s role in managing drug therapy is very important.¹⁰

Considering specificities underlying HSCT, and a lack of information regarding pharmacists’ collaboration in the care of patients undergoing this therapeutic modality, the present systematic review aimed to identify studies that address the contribution of pharmaceutical services on HSCT treatment.

Methods

A systematic literature review was conducted according to guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes¹¹ and was previously registered in the International Prospective Register of Systematic Reviews, registration number CRD42017062391.¹² We selected publications that addressed the following research guiding question: “How clinical services performed by pharmacists contribute to HSCT outcomes?” Observational or experimental studies describing results of clinical services provided by pharmacists during HSCT were included. The following types of articles were excluded:

Articles that only conceptually described clinical pharmacy services during HSCT, specialist’s comments or opinions, study protocols, reviews (narratives, integrative, or systematic), dissertations or theses, editorials, news, and abstracts published in annals of congresses;

Articles presenting results of clinical services performed by pharmacists during HSCT with results from other hospital sectors, without separating outcomes by sector;

Articles that reported multidisciplinary team services during HSCT and did not separately present activities and outcomes of clinical pharmacy services;

Articles published in languages other than English, Portuguese, or Spanish;

Publications that did not have full text available.

When constructing the literature search strategy, we considered the incorporation of terms that characterized our guiding question, structured by the acronym PICO (population: patients undergoing HSCT; intervention: clinical services performed by pharmacists; comparison: absence of a clinical pharmacist; outcomes: outcomes were not defined in this search step so as to not attribute undesired specificity).¹³ This strategy was prepared using an association of terms from the MeSH vocabulary thesaurus (Medical Subjects Headings) in PubMed (MEDLINE—Medical Literature Analysis and Retrieval System Online/PubMed) (Table 1) and was adapted for the other databases we searched: CENTRAL (The Cochrane Central Register of Controlled Trials/The Cochrane Library), EMBASE, SCOPUS, and LILACS (Scientific and Technical Literature of Latin America and the Caribbean/Virtual Health Library). The search was conducted in April 2017.

Table 1.

Strategy used to literature search.

Search strategy^a	Subject descriptor (MeSH terms)	Relevant keywords
1	“Bone Marrow Transplantation”; “Stem Cell Transplantation”; “Hematopoietic Stem Cell Transplantation”	“Bone Marrow Transplantation”; “Transplantation, Bone Marrow”; “Grafting, Bone Marrow”; “Bone Marrow Grafting”; “Bone Marrow Cell Transplantation”; “Transplantation, Bone Marrow Cell”; “Stem Cell Transplantation”; “Stem Cell Transplantations”; “Transplantations, Stem Cell”; “Transplantation, Stem Cell”; “Hematopoietic Stem Cell Transplantation”; “Transplantation, Hematopoietic Stem Cell”; “Stem Cell Transplantation, Hematopoietic”; “Allogenic Stem Cell Transplantation”
2	“Pharmacy Service, Hospital”; “Pharmaceutical Services”; “Pharmacists”	“Pharmacy Service, Hospital”; “Hospital Pharmaceutical Service”; “Hospital Pharmaceutical Services”; “Pharmaceutical Services, Hospital”; “Services, Hospital Pharmaceutical”; “Pharmaceutical Service, Hospital”; “Pharmaceutic Service, Hospital”; “Hospital Pharmacy Services”; “Pharmacy Services, Hospital”; “Services, Hospital Pharmacy”; “Service, Hospital Pharmacy”; “Hospital Pharmacy Service”; “Hospital Pharmaceutic Service”; “Hospital Pharmaceutic Services”; “Pharmaceutic Services, Hospital”; “Services, Hospital Pharmaceutic”; “Service, Hospital Pharmaceutic”; “Service, Hospital Pharmaceutical”; “Pharmacy Service, Clinical”; “Service, Clinical Pharmacy”; “Clinical Pharmacy Services”; “Pharmacy Services, Clinical”; “Services, Clinical Pharmacy”; “Clinical Pharmacy Service”; “Pharmaceutical Services”; “Services, Pharmaceutic”; “Services, Pharmacy”; “Pharmaceutic Services”; “Pharmaceutic Service”; “Service, Pharmaceutic”; “Services, Pharmaceutical”; “Pharmaceutical Service”; “Service, Pharmaceutical”; “Pharmacy Services”; “Pharmacy Service”; “Service, Pharmacy”; “Pharmaceutical Care”; “Care, Pharmaceutical”; Pharmacists; Pharmacist; “Clinical Pharmacists”; “Clinical Pharmacist”; “Pharmacist, Clinical”; “Pharmacists, Clinical”

Search strategies 1 and 2 were combined using the Boolean operator AND, MeSH terms and each keyword were combined using OR.

The selection of articles was conducted using an app for systematic reviews: Rayyan.¹⁴ First, duplicate articles across databases were removed. Next, the title and abstract of each publication were read and critically analyzed in accordance with our research question, inclusion and exclusion criteria, with the aim of screening articles of interest for full text reading. If the researcher could not determine whether to exclude an article based on its abstract and title, then it was retrieved for full text reading. To avoid bias during screening, we designated two researchers (MOBZ and ACBZ) to independently perform this aforementioned step. In order to verify the degree of agreement between researchers, a Kappa coefficient was calculated with a 95% confidence interval.¹⁵ Disagreements between the two researchers were resolved through discussion and consensus.

After screening potential publications, the remaining articles were fully analyzed by the same researchers. All publications had full text available and were written in English. At this stage, inclusion into the systematic review was determined. In an attempt to identify any other relevant publications that the initial search strategy might not have covered, we searched the reference lists of all selected articles. Finally, two articles were randomly selected for a pilot test of the data extraction procedure based on recommendations from the Cochrane Reviewers’ Handbook.¹⁶ From here, the extraction of data concerning variables of interest from each article commenced and was organized into table form.

The quality of included studies was assessed using the modified Downs and Black – Checklist for measuring study quality.^17,18 This tool allows evaluation of methodological quality, external and internal validity, and statistical power of scientific publications, including observational studies. This modified instrument can reach a maximum score of 28, and each article was analyzed, scored, and ranked as excellent (24–28 points), good (19–23 points), medium (14–18 points), or poor (<14 points).

Results

After applying the search strategy, a total of 1838 publications were screened in terms of titles and abstracts. During this process, a Kappa coefficient of 0.89 was obtained, which corresponds to near perfect agreement (0.80–1.00) between the two researchers.¹⁵ Two publications in which there was disagreement were excluded after discussion and consensus. Finally, seven articles were considered adequate for inclusion in the systematic review. Figure 1 displays the process involved during study selection.

Among the studies included, four were performed in HSCT outpatient clinics,^8,9,19,20 two in HSCT inpatient clinics^21,22 and one in both settings.²³ Regarding the type of transplantation, four publications included both patients undergoing autologous and allogeneic HSCT;^20–23 the others included only patients undergoing allogeneic HSCT.^8,19 Concerning the year of publication, most articles were published in the last five years.^8,9,19,22,23 Four surveys were conducted in North America,^19–21,23 one in South America,⁹ one in Asia,²² and one in Oceania.⁸

The activities performed by clinical pharmacists were quite varied, including identification and solution of PRPs, participation in discussions with clinical teams, drug reconciliation, patient and team education regarding pharmacotherapy, preparation of guidelines and educational materials, and evaluation of medication adherence.

Concerning the applicability of clinical pharmacists working within an HSCT clinical team, there was unanimity of positive references. In other words, all studies reported that clinical pharmacists were necessary and beneficial in both outpatient and inpatient settings. Moreover, one of the selected articles illustrated that a pharmacist is not only clinically useful but also brings humanistic and economic benefits to HSCT treatment.²³ Study descriptions and methodological procedures are summarized in Tables 2 and 3.

Table 2.

Characteristics of included studies (n = 7).

Author (origin)	Study design (according to the authors)	Sample (n)	Place of performance data collection	Time of follow-up	Study aim
Corrêa et al. (Porto Alegre, Brazil)⁹	Quasi-experimental design with a comparison group	IG: 22; CG: 44; 5–60 years old	Outpatient clinic	Six months	To evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range.
Alexander et al. (Chapel Hill, USA)²³	Three-phase study. Phases 1 and 2: pharmacoeconomic studies; phase 3: cohort	Phase 1: 170 inpatients and 290 outpatients; phase 2: not described; phase 3: 135 survey respondents (85 patients and 50 providers)	Inpatient and outpatient settings	Phase 1: six months; phase 2: six weeks; phase 3: not described	To evaluate the economic and humanistic impact of pharmacists’ involvement in the care of patients undergoing HSCT.
Mousavi et al. (Tehran, Iran)²²	Randomized clinical trial	IG: 29; CG: 30; >18 years old	Inpatient clinic	Three months	To evaluate the effect of a clinical pharmacist-based PN service on nutritional status, clinical outcomes and PN therapy complications after HSCT in adult patients.
Chieng et al. (Melbourne, Australia)⁸	Prospective cohort	EG: 23; CpG: 0; >18 years old	Outpatient clinic	Six visits (weekly)	To evaluate the effectiveness of a clinical pharmacist working in an ambulatory HSCT clinic.
Ho et al. (Toronto, Canada)¹⁹	Pilot project – design not described	SG: 35; no mention of age	Outpatient clinic	Most patients (n = 28) were seen in three or more weekly visits	To determine the effect on medication safety of, as well as potential barriers to, incorporating a pharmacist in the multidisciplinary team of an allo-HSCT clinic.
Prot-Labarthe et al. (Montreal, Canada)²¹	Descriptive	SG: 29; <18 years old	Inpatient clinic	31 no-consecutive days	To describe pharmacist interventions in an HSCT pediatric inpatient clinic.
Taylor et al. (Toronto, Canada)²⁰	Prospective descriptive	31 Children from a HSCT clinic; 27 children from an oncology clinic; 0.5–19 years old	Outpatient clinic	2.3 Visits (range 0–9) for HSCT patients and 1.3 visits (range 1–2) for oncology patients.	To characterize the drug-related needs, describe the role of the pharmacist, and assess the impact of clinical pharmacy services in patient care in a pediatric hematology/oncology clinic.

CG: control group; CpG: comparison group; EG: exposed group; HSCT: hematopoietic stem cell transplantation; IG: intervention group; PN: parenteral nutrition; SG: single group.

Table 3.

Characteristics of included studies (n = 7).

Author (origin)	Pharmacist activities	Indicators/evaluation tools	Outcomes
Corrêa et al. (Porto Alegre, Brazil)⁹	Pharmacotherapy follow-up, allowing to identify PRPs and their causes, discuss with clinical team, propose changes when necessary, and educate the patients regarding pharmacotherapy.	Maintenance of the immunosuppressive serum levels within the desired range.	CG displayed 65% of the proper serum levels of immunosuppressive agents, while in IG the percentage was 82% (p = 0.004).
Alexander et al. (Chapel Hill, USA)²³	Pharmacotherapy follow-up of inpatients and outpatients, pharmaceutical interventions, discharge counseling, patient education regarding pharmacotherapy.	Phase 1: pharmaceutical services translated to revenue generated; phase 2: pharmaceutical services translated to time savings; phase 3: patients and providers survey to assess their perceptions of pharmacists.	Phase 1: for inpatients, there was an average discharge prescription revenue of U$990 per patient; in the outpatient clinic, pharmacist visits generated approximately U$80 per patient. Phase 2: pharmacists’ activities led to a total time savings of 122 h in six weeks. Phase 3: patients and providers met the predetermined 80% positive response rate for most survey items.
Mousavi et al. (Tehran, Iran)²²	The clinical pharmacists implemented standard guidelines of nutrition support with PN being prepared based on patient’s individual requirements under a standard aseptic condition.	Nutritional status (weight, albumin, total protein, pre-albumin, and nitrogen balance), length of hospital stay, time to engraftment, rate of GVHD, and mortality rate.	All nutritional outcomes were either preserved or improved in the IG, while the nutritional status in the CG was deteriorated (p < 0.01). Length of hospital stay was significantly shorter in the IG (p < 0.01). Days to engraftment did not differ (p = 0.78). Six patients in the CG had severe GVHD and two of them died. One patient in the IG had severe GVHD.
Chieng et al. (Melbourne, Australia)⁸	The clinical pharmacist performed medication reviews, drug reconciliation, identified and solved potential PRPs (interventions), and assessed medication adherence.	Number of interventions; potential consequence if the intervention had not occurred (multidisciplinary risk rating panel); medication adherence (Morisky score and review of dose administration aids).	A total of 161 interventions were recorded, being 40% high-risk interventions, 46% medium risk and 14% low risk. Morisky scores improved by an average of 1.53 (p < 0.0001) between visits 1 and 6. All patients were scored as highly adherent by visit 6.
Ho et al. (Toronto, Canada)¹⁹	The pharmacists’ primary task was to perform drug reconciliation and to identify and solve PRPs. He also provided education regarding pharmacotherapy to patients and clinical team. The pharmacist helped to clarify prescriptions and drug coverage issues with the outpatient pharmacy.	Number and clinical significance of medication discrepancies and interventions (graded by a panel of clinicians); patient and clinical team satisfaction with pharmacists’ work survey.	Pharmacists identified a total of 50 medication discrepancies and 70 PRPs; 20 of the 21 unintentional medication discrepancies and 7 of the 10 undocumented intentional medication discrepancies were graded as clinically or moderately significant. Satisfaction survey reported a positive response supporting pharmacists’ work.
Prot-Labarthe et al. (Montreal, Canada)²¹	During a pharmaceutical care specialized residency program, the pharmacist should identify PRPs and solve them through interventions.	Number of PRPs and number, acceptability and clinical impact of pharmaceutical interventions.	A total of 525 interventions were collected. The main PRPs were adverse drug reactions (23.8%), untreated indication (17.5%), and failure to receive drug (17.0%). Among the 324 interventions needing physician’s approval, 93.2% were accepted without change. Most interventions (81.5%) were estimated to have positive or major clinical impact.
Taylor et al. (Toronto, Canada)²⁰	The pharmacist should identify actual or potential PRPs during patient/parent dialogue and make interventions with the physician and/or patient/parent.	Number of PRPs and number, acceptability, and clinical impact of pharmaceutical interventions.	165 PRPs were identified, a mean of 4.8 PRPs per patient in HSCT patients and 0.6 in oncology patients, 91% of the PRPs were in HSCT patients. 177 interventions were made by the pharmacist, being 127 for HSCT patients; 81% were accepted by the physician and/or patient/parent. 83.5% had a positive impact on patient care.

CG: control group; GVHD: graft-versus-host disease; HSCT: hematopoietic stem cell transplantation; IG: intervention group; PN: parenteral nutrition; PRPs: pharmacotherapy-related problems.

Table 4 presents the quality assessments for included studies. Only one publication reached a score considered to be good,²² three manuscripts were classified as medium quality,^8,9,23 and the remaining three were rated as poor quality.^19–21

Table 4.

Methodological quality of included studies (n = 7).

References	Reporting										External validity			Internal validity – bias							Internal validity – confounding (selection bias)						Power	Score
References	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20	21	22	23	24	25	26	27	Score
Downs and Black appraisal criteria
Corrêa et al.⁹	✓	✓	✓	✓	X	✓	✓	X	✓	✓	✓	✓	✓	X	X	✓	✓	✓	✓	✓	✓	X	X	X	X	✓	X	18
Alexander et al.²³	X	✓	✓	✓	✓	✓	✓	X	X	✓	X	X	✓	X	X	✓	X	✓	✓	✓	X	X	X	X	✓	X	X	14
Mousavi et al.²²	✓	✓	✓	✓	✓	✓	✓	✓	✓	✓	X	X	✓	✓	X	✓	✓	✓	✓	✓	✓	✓	✓	X	✓	✓	X	22
Chieng et al.⁸	✓	✓	✓	✓	X	✓	✓	X	✓	✓	X	X	✓	X	X	✓	✓	✓	✓	✓	X	X	X	X	X	✓	X	15
Ho et al.¹⁹	✓	✓	X	✓	X	✓	✓	X	X	X	X	X	✓	X	X	✓	X	✓	✓	✓	X	X	X	X	X	✓	X	11
Prot-Labarthe et al.²¹	✓	✓	X	✓	X	✓	✓	✓	✓	X	X	X	✓	X	X	✓	X	✓	X	✓	X	X	X	X	X	✓	X	12
Taylor et al.²⁰	✓	✓	✓	✓	X	✓	✓	✓	X	X	X	X	✓	X	X	✓	X	✓	✓	✓	X	X	X	X	X	X	X	12

✓: yes; X: no or unable to determine; 1: hypotheses/aims/objectives clearly stated; 2: main outcome measures clearly described; 3: characteristics of patients/subjects clearly described; 4: interventions of interest clearly described; 5: distribution of principal confounders in each group clearly described; 6: main findings clearly described; 7: estimates of random variability in the data provided; 8: important adverse events reported; 9: characteristics of patients lost to follow-up described; 10: actual probability values reported; 11: participants approached representative of entire population; 12: participants recruited representative of entire population; 13: staff, places, and facilities representative of majority of population; 14: blinding of study subjects; 15: blinding of assessors; 16: data based on data-dredging clearly stated; 17: adjustment of different length of follow-up or duration between case and control; 18: appropriate statistical tests used; 19: compliance to intervention reliable; 20: main outcome measure reliable and valid; 21: intervention groups or case-controls recruited from same population; 22: intervention groups or case-controls recruited at the same time; 23: study subjects randomized to the interventions; 24: was concealed randomization to allocation undertaken; 25: adequate adjustment made in the analysis of confounders; 26: patient losses accounted for; 27: sufficiently statistical power.

Discussion

The scientific literature has been able to emphasize the importance of clinical pharmacists working in oncology and hematology settings.^24–28 However, the present systematic review did not obtain a robust number of publications that addressed the role of pharmacists within a specific HSCT context, and most of the included studies presented poor or medium quality. As expected, quality scores were consistent with issues regarding methodological design and level of evidence provided, with randomized clinical trials representing the highest publication quality. Scores decreased in order from quasi-experimental studies, to cohort designs, to descriptive studies.

The complex and multidisciplinary nature of HSCT patient care is another factor that could impact the lower quality of studies published in this area. Associating the gold standard of HSCT clinical outcomes (transplant-related mortality, disease relapse, duration of hospitalization, or presence and stage of GVHD) to a single intervention, such as the role of a clinical pharmacist within a multidisciplinary team, is quite challenging.⁴ The success of these outcomes is a product of commitment within the entire team, working in an integrated and cohesive patient-centered manner. For this reason, six of the seven studies reviewed chose to evaluate secondary clinical outcomes (maintenance of serum immunosuppressive levels, medication adherence, number and impact of pharmaceutical interventions) or economic and humanistic outcomes, which may be positively impacted by a clinical pharmacist and are easier to measure.

The fact that most of the articles reviewed were published in the last five years is consistent with the expansion of pharmaceutical clinical services, especially as the population ages.^29,30 Currently, there is a worldwide effort toward making pharmacy curricula more focused on clinical practice, with an eye toward multidisciplinary patient-centered care and evidence-based practices. The increase in clinical pharmacy residency programs has also become an important resource for training in this regard.^29,31 Within the context of HSCT, there is a growing need for clinical pharmacists, as this therapeutic modality is being applied to patients with an increasingly advanced age and present with other comorbidities; this favors the use of an even greater number of medications.³²

Another finding of interest was the number of articles from North America. This is not surprising giving that the United States and Canada are at the forefront of clinical pharmacy expertise, with solid training within their university systems.^29,31

Although there were a small number of articles discussing the topic under analysis, and many provided limited evidence, it is notable that each article was unanimous in confirming the positive impact of a pharmacist’s contributions to clinical practice during HSCT. Furthermore, pharmaceutical clinical services described in the present review favored the control and prevention of PRPs, the maintenance of immunosuppressive serum levels within an adequate range, improvement in patients’ clinical and nutritional status, facilitation of medication adherence, and economic gains to the healthcare system. Clinical pharmacy is a useful tool within the HSCT inpatient clinic, during pre- and post-transplantation, and within the outpatient clinic, during immediate and late post-HSCT. Moreover, pharmacists contribute to the success of this therapeutic modality across different age groups, not just middle-aged and older adults.

In one study developed by Corrêa et al.,⁹ the pharmacist implemented pharmacotherapeutic follow-up for patients in an allogeneic HSCT outpatient clinic according to the Dáder method. This model of practice allowed for the identification of PRPs, the establishment of therapeutic goals, and the development of strategies to achieve those goals through discussions with the clinical team, interventions, and educational activities regarding pharmacotherapy. Here, the researchers opted to evaluate the maintenance of immunosuppressive serum levels within the therapeutic range. The presence of the pharmacist in the multidisciplinary team helped patients to be more successful in achieving this therapeutic goal.

Researches by Chieng et al.⁸ and Ho et al.¹⁹ also included patients from an allogeneic HSCT outpatient clinic. In the first, the pharmacist conducted interviews to review pharmacotherapy and perform drug reconciliation, detected, and solved PRPs, and monitored medication adherence. In the second, clinical services comprised PRP identification and solution, along with pharmacotherapy education; however, the main focus was drug reconciliation. Similarly, Taylor et al.²⁰ studied the pharmacist’s contribution to PRP perceptions and solutions within the context of both autologous and allogeneic transplantation. These three studies produced results that corroborate the notion that pharmaceutical clinical services help improve pharmacotherapy management and patient safety from a post-HSCT perspective.

Mousavi et al.²² verified the applicability of a clinical pharmacist within an HSCT inpatient clinic by providing parenteral nutritional support based on a patient’s individual needs. This activity significantly improved patients’ nutritional status and clinical outcomes. Also within an HSCT inpatient clinic, Prot-Labarthe et al.²¹ evaluated the number of PRPs identified and solved through pharmaceutical interventions. The pharmacist’s involvement in patient-centered care provided clinically relevant interventions, which were mostly accepted without modification from the broader clinical team.

Alexander et al.’s²³ study aims differed from other articles included in this review, as they chose to investigate the economic impact of a pharmacist’s involvement during HSCT. Here, each patient paid fees for clinical services provided by the pharmacist; thus, the researchers were able to use previous billing charges, prescription revenues, and time-saving data to estimate economic impact. Results revealed that such measures increased income and saved time.

Clinical pharmacists’ contributions were also recognized from the perspective of patients and the HSCT clinical team. To assess the humanistic impact of a pharmacist’s role, Alexander et al.²³ also developed and validated a survey designed to assess expectations, experiences, and perceptions regarding the value of pharmacist activities during HSCT. Both patients and team members had an 80% positive response rate for most survey items. Ho et al.¹⁹ also conducted a satisfaction survey administered to patients and health professionals, whose responses validated the inclusion of a pharmacist as part of the HSCT multidisciplinary team. The high acceptability of pharmaceutical interventions was also a finding that illustrates team and patient support for clinical pharmacy. This was observed by Prot-Labarthe et al.,²¹ where the acceptance rate was 93.2%; Taylor et al.²⁰ obtained an acceptability of 81%.

On balance, this systematic review was able to demonstrate that the inclusion of clinical pharmacists into an HSCT team facilitates effective pharmacotherapeutic results, regardless of transplantation type, recipient age, or clinical setting (inpatient or outpatient). Nonetheless, more robust and higher quality studies are needed to highlight the positive impact of pharmaceutical clinical services within a clinical, economic, and humanistic HSCT context, particularly randomized clinical trials developed in accordance with the Consolidated Standards of Reporting Trial recommendations. Considering that in HSCT it is a challenge to relate a single intervention, such as the pharmacist clinical services, with changes in survival, duration of hospitalization and presence of GVHD, surrogate outcomes may be employed, for example: rehospitalization rates, maintenance of calcineurin inhibitor plasma levels within a predefined range, vaccination status post-HSCT, blood pressure or lipid control, decrease glycated hemoglobin in steroid-induced diabetes, medication adherence.^4,10 These outcomes are known to have a positive impact on clinical course and may be affected by pharmaceutical clinical services. Economic and humanistic outcomes should also be evaluated.⁴

The main limitation of this systematic review was the fact that the search strategy did not cover the gray literature. Therefore, non-scientific articles were not included. Hence, this review may underestimate the actual participation levels of clinical pharmacists in HSCT treatment, given that many professionals do not publish results of their work. A questionnaire applied to members of the American College of Clinical Pharmacy revealed that only 19% of respondents presented or published results of their work on the management of pharmacotherapy in oncology.²⁷ Clearly, clinical pharmacists need support and encouragement in order to document and disseminate their work so as to facilitate the expansion of clinical services within other institutions.

Conclusions

The present systematic review indicates that pharmacists are contributing to the care of patients undergoing autologous and allogenic HSCT, especially through the identification and solution of PRPs, participation in discussions with clinical teams, drug reconciliation, patient and team education regarding pharmacotherapy, preparation of guidelines and educational materials, and evaluating medication adherence. All things considered, the present results revealed that these services could improve clinical, humanistic, and economic outcomes related to HSCT. However, a limited number of researchers are able to study and disseminate these results to the broader scientific community. To improve this deficiency, it is essential to produce more quality research that underscores clinical pharmacists’ contribution to positive HSCT outcomes.

Supplemental Material

Supplemental material for Clinical pharmacists’ contributions to hematopoietic stem cell transplantation: A systematic review

Supplemental material for Clinical pharmacists’ contributions to hematopoietic stem cell transplantation: A systematic review by Maria Olívia Barboza-Zanetti, Ariane Cristina Barboza-Zanetti, Samir Antonio Rodrigues-Abjaude, Belinda Pinto-Simões and Leonardo Régis Leira-Pereira in Journal of Oncology Pharmacy Practice

Footnotes

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Supplementary material

Online supplementary data is available at

References

Passweg

Baldomero

Bader

et al.

Hematopoietic stem cell transplantation in Europe 2014: more than 40,000 transplants annually. Bone Marrow Transplant 2016; 51: 786–792.

Niederwieser

Baldomero

Szer

et al.

Hematopoietic stem cell transplantation activity worldwide in 2012 and a SWOT analysis of the Worldwide Network for Blood and Marrow Transplantation Group including the global survey. Bone Marrow Transplant 2016; 51: 778–785.

Gratwohl

Baldomero

Aljurf

et al.

Hematopoietic stem cell transplantations: a global perspective. JAMA 2010; 303: 1617–1617.

Merten

Shapiro

Gulbis

et al.

Utilization of collaborative practice agreements between physicians and pharmacists as a mechanism to increase capacity to care for hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2013; 19: 509–518.

Glotzbecker

Duncan

Alyea

et al.

Important drug interactions in hematopoietic stem cell transplantation: what every physician should know. Biol Blood Marrow Transplant 2012; 18: 989–1006.

Chieng

Coutsouvelis

Poole

et al.

Implementation of a clinical pharmacy service to an allogeneic stem cell transplant ambulatory clinic. J Pharm Pract Res 2014; 44: 105–107.

Bauters

Vinent-Genestar

Delaney

et al.

Role of the clinical pharmacist in a paediatric haemato-oncology stem cell transplantation ward. Eur J Hosp Pharm 2014; 21: 309–312.

Chieng

Coutsouvelis

Poole

et al.

Improving the transition of highly complex patients into the community: impact of a pharmacist in an allogeneic stem cell transplant (SCT) outpatient clinic. Support Care Cancer 2013; 21: 3491–3495.

Corrêa

Zuckermann

Fischer

et al.

Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution. Pharm Pract 2016; 14: 683–683.

10.

Clemmons AB, Alexander M, DeGregory K, et al. The hematopoietic cell transplant pharmacist: roles, responsibilities, and recommendations from the ASBMT pharmacy special interest group. Biol Blood Marrow Transplant 2017; 24: 914–22.

11.

Moher

Liberati

Tetzlaff

et al.

Guidelines and guidance preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009; 6: 1–6.

12.

Zanetti MOB, Zanetti ACB, Abjaude SA, et al. Contributions of clinical pharmacists in the hematopoietic stem cell transplantation: a systematic review. PROSPERO 2017 CRD42017062391, www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42017062391 (2017, accessed 25 March 2018).

13.

Santos

CMC

Pimenta

CAM

Nobre

MRC

. The PICO strategy for the research question construction and evidence search. Rev Lat Am Enfermagem 2007; 15: 508–511.

14.

Ouzzani

Hammady

Fedorowicz

et al.

Rayyan – a web and mobile app for systematic reviews. Syst Rev 2016; 5: 1–10.

15.

Cohen

. A coefficient of agreement for nominal scales. Educ Psychol Meas 1960; 20: 37–46.

16.

Higgins JPT and Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration, http://handbook.cochrane.org (2011, accessed 26 March 2018).

17.

Downs

Black

. The feasibility of creating a checklist for the assessment of the methodological quality both of randomized and non-randomized studies of health care interventions. J Epidemiol community Heal 1998; 52: 377–384.

18.

O’Connor

Tully

Ryan

et al.

Failure of a numerical quality assessment scale to identify potential risk of bias in a systematic review: a comparison study. BMC Res Notes 2015; 8: 224–224.

19.

Akada

Messner

et al.

Pharmacist’s role in improving medication safety for patients in an allogeneic hematopoietic cell transplant ambulatory clinic. Can J Hosp Pharm 2013; 66: 110–117.

20.

Taylor

Dupuis

Nicksy

et al.

Clinical pharmacy services in a pediatric hematology/oncology clinic: a description and assessment. Can J Hosp Pharm 1999; 52: 18–23.

21.

Prot-Labarthe

Therrien

Demanche

et al.

Pharmaceutical care in an inpatient pediatric hematopoietic stem cell transplant service. J Oncol Pharm Pract 2008; 14: 147–152.

22.

Mousavi

Hayatshahi

Sarayani

et al.

Impact of clinical pharmacist-based parenteral nutrition service for bone marrow transplantation patients: a randomized clinical trial. Support Care Cancer 2013; 21: 3441–3448.

23.

Alexander

Rao

Khan

et al.

Pharmacists’ impact in hematopoietic stem-cell transplantation: economic and humanistic outcomes. J Oncol Pract 2016; 12: e118–e126.

24.

Ruder

Smith

Madsen

et al.

Is there a benefit to having a clinical oncology pharmacist on staff at a community oncology clinic?

J Oncol Pharm Pract 2011, pp. 17, 425–432.

25.

Farias

Aguiar

Rotta

et al.

Implementing a clinical pharmacy service in hematology. Einstein 2016; 14: 384–390.

26.

Leveque

Delpeuch

Gourieux

. New anticancer agents: Role of clinical pharmacy services. Anticancer Res 2014; 34: 1573–1578.

27.

Holle

Harris

Chan

et al.

Pharmacists’ roles in oncology pharmacy services: results of a global survey. J Oncol Pharm Pract 2017; 23: 185–194.

28.

Delpeuch

Leveque

Gourieux

et al.

Impact of clinical pharmacy services in a hematology/oncology inpatient setting. Anticancer Res 2015; 35: 457–460.

29.

Carter

. Evolution of clinical pharmacy in the USA and future directions for patient care. Drugs Aging 2016; 33: 169–177.

30.

Gubbins

Micek

Badowski

et al.

Innovation in clinical pharmacy practice and opportunities for academic-practice partnership. Pharmacother J Hum Pharmacol Drug Ther 2014; 34: e45–e54.

31.

Nunes-Da-Cunha I, Arguello B, Martinez FM, et al. A comparison of patient-centered care in pharmacy curricula in the United States and Europe. Am J Pharm Educ 2018; 80: 1–12.

32.

Komanduri

. Pharmacists and physicians in hematopoietic stem cell transplantation: advances and opportunities to use collaborative practice agreements to improve care. Biol Blood Marrow Transplant 2013; 19: 505–508.

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