Role of pharmacists in the context of rare diseases: a scoping review protocol

Abstract

Introduction

Rare diseases are chronic conditions, generally incurable, progressive and disabling, which may result in early death. Access to therapeutic products, both medicines and appropriate medical devices, is essential to prevent the progression of the disease and maintain the patients’ quality of life. Pharmacists can be part of health teams, in charge of guiding patients’ journey, monitoring pharmacotherapy and identifying risks. This scoping review aims to identify and summarise evidence on the role of pharmacists and its impact in the field of rare diseases.

Methods and analysis

The searches will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline for protocols. Three electronic databases will be consulted. Studies reporting on qualitative and/or quantitative data from any world region will be considered. There will be no language or initial time limit for studies inclusion, until December 2022. To be eligible for inclusion, studies must focus on the role pharmacists in clinical services aimed at promote the access to medicines, prevention and resolution of problems related to pharmacotherapy. No assessments of items’ quality will be made, as the purpose of this scoping review is to synthesise and describe the coverage of the evidence. Clinical, humanistic or economic outcomes from studies that meet the inclusion criteria will be included in the review. The analysis will synthesise the available evidence and may be able to push pharmaceutical practice forward, aiding professionals, educators and managers in the implementation of new approaches to better meet the needs of rare diseases and providing opportunities for future research.

Ethics and dissemination

Primary data will not be collected in this study and formal ethical approval is not required. The findings of this study will be disseminated through peer-reviewed publications and conference presentations.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• This scoping review protocol is the first to evaluate the role of the pharmacist in wide range of rare health conditions.

• This protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews tool, in order to systematise the search, screening and presentation of results.

• The results of this study are of interest to interprofessional healthcare teams, aiming to improve treatment outcomes for rare health conditions.

• This list of rare diseases for the search was established by consulting advisory documents of the health systems of Brazil, the UK, Ireland, the USA and China.

Introduction

Rare diseases are health conditions that affect a small number of people when compared with prevalent diseases. No universal definition exists for rare diseases; however, the prevalence threshold is the most commonly used descriptor,¹ which provides a measure of the population burden of the disease.² However, there are different edges described around the world. In the USA, rare diseases are defined as a health condition which affects fewer than 200 000 patients in the country.³ The European Union identifies a rare disease as a health chronically debilitating condition affecting no more than 5 in 10 000 people.⁴ Other national definitions translate to prevalence ranging from 5 to 76 per 100 000.¹ In each jurisdiction, the prevalence threshold is the indicator for the planning and development of actions and services to support the health needs of these patients, according to their health systems.²

Most rare diseases are chronic, cause disabilities, affect the quality of life of patients and their families, and may result in early death. According to the Orphanet database, 6000 clinically defined rare diseases are estimated, that affect at least 3.5%–5.9% of the worldwide population; 71.9% of which are genetic and 69.9% are exclusively paediatric onset.²

Despite the heterogeneity of each health condition, patients with rare diseases may share similar difficulties, such as the obstacles to being diagnosed correctly; the absence of specific pharmacological therapies; the difficulties in accessing technologies due to patents and/or legislations and regulations.^5–8

The price of medicines for the treatment of rare diseases, despite growing supply on the world market, exceeds the ability of individuals, health insurance companies, or even governments in high-income countries, to pay for them.⁹ Furthermore, it should also be considered that diagnosis and treatment advances made in medicine in recent decades have increased the life expectancy of people with rare diseases, allowing for the emergence of new-age groups of people who previously did not live past childhood. These changes result in higher costs for health systems and reflect the need for more rational treatment regimens over the years.^{10 11}

Most medicines for the treatment of rare diseases require special care in the supply chain and their use requires clinical monitoring due to dose adjustments and adverse effect profiles. Some of them are injectable, requiring individual skills and/or specialised environments for infusion. Patients need assistance that covers support for accessibility, guidelines for administration and monitoring performed by specialised professionals.¹²

Pharmacists are professionals with specific training to meet medication-related needs. They help to avoid accessibility and/or pharmacotherapy problems, such inadequate dosage, inadequate administration, lack of adherence to the prescribed treatment, drug–drug and drug–food interactions and adverse drug events.¹³ Furthermore, pharmacists may be part of health teams, tasked with providing guidance and training to patients and monitoring pharmacotherapeutics, thus, assisting in the treatment decision-making, identification of risks and optimise the expenditures for pharmacological treatments borne by the national healthcare systems.^{14 15}

However, studies on pharmaceutical services and their benefits for rare diseases are scattered and focused on specific diseases. Health systems around the world may be hampered by the absence of information to support or not support the classification of a condition as rare, resulting in difficulties in recognising rare diseases and the patient’s needs. As a consequence, there is a lack of epidemiological data and difficulties in the organisation and planning of services.¹⁶

Despite the availability of reports on the Orphanet¹⁷ website that provide extensive lists of rare diseases, in the present study, a specific list of diseases is proposed. It is based on the rare conditions defined and listed by the countries that have recognised these diseases in their territories and in their health systems. For this, two criteria are considered:

1. Countries that have published a list of rare diseases in scientific literature whose diseases are recognised by their official bodies. For this case, one of them is Brazil¹⁸ which has published a list of rare diseases drawn from official documents and guidelines of the Brazilian public health system. Another one is China,¹⁹ whose proposed list has been published jointly by five Chinese national bodies.

2. Countries that recognise rare diseases and develop or evaluate health services for these conditions. On this criterion, the USA²⁰ assessed the total economic burden of 379 rare diseases. Also the UK²¹ whose public health service has developed a guidance programme about highly specialised technology, and the Ireland²² which assessed the role of primary care in the Irish journey of care for patients with rare diseases.

Regardless of important innovations in diagnostic and therapeutic areas, many rare health conditions still lack specific therapies, which increases the need for preventive measures and multidisciplinary follow-ups. While practice standards for interprofessional care have been published for some rare conditions, patients can receive care from providers who have little knowledge or experience with the disease.^23–26 In this sense, improving therapeutic management in services, including that of available pharmacological treatments, is a fundamental demand that has the potential to reduce costs and provide a better quality of life for those with rare health conditions.

Scoping review objectives

The objective of this scoping review is to identify and summarise the role of pharmacists and their impact in the management of rare diseases. This review aims to answer the following study question: in the context of rare diseases, what are the activities or interventions performed by pharmacists reported in the literature, and what is their impact?

This protocol details the scoping review’s methodological and analytical approaches, informed by the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) reporting guideline for protocols.

Methods

The scoping review will use the PRISMA extension for Scoping Reviews tool.^{27 28} It will include the following steps: (1) identifying the title and research question; (2) writing the introduction; (3) defining the search strategy; (4) developing the inclusion criteria; (5) selecting studies; (6) extracting key findings from eligible studies that may answer the research question; and (7) analysing, presenting and summarising the results.²⁷

Search strategy and terms

The terms used in the search for the articles were chosen from those found in Medical Subject Headings (MeSH) and relevant articles retrieved in preliminary searches. In addition to the descriptors for the term ‘rare diseases’, a list of rare diseases was compiled to be used in the literature search.

This list of rare diseases for the search (online supplemental table 1) was established by consulting advisory documents of the health systems of Brazil, the UK, Ireland, the USA and China. When the same rare disease was cited in all documents, it became part of the list of diseases for the literature search. The following documents were analysed:

1. Brazil: drug recommendations for rare diseases issued by the National Commission for Health Technology Incorporation (CONITEC) in the Brazilian public health system (SUS)¹⁸;

2. China: the first official list of Chinese rare diseases¹⁹;

3. USA: an evaluation study of the economic burden of 379 rare diseases in the country in 2019²⁰;

4. UK: a highly specialised technologies guidance for the British health system issued by the National Institute for Health and Care Excellence²¹;

5. Ireland: an evaluation of the involvement of general practitioners in the care management of patients with 22 rare diseases mentioned in the survey by the Irish National Rare Diseases Office.²²

The Orphanet Portal²⁹ was used to search for the synonyms of rare diseases to identify similarities between the lists considered.

The health librarian at our institution helped in the definition of the electronic databases. The searches will be carried out in the PubMed, Scopus and Cumulative Index to Nursing and Allied Health databases based on a search strategy adapted for each of them.

The studies will not be limited by language. There will be no initial time limit for included studies, and 31 December 2022 will be considered the final date for searches.

Final search strategy by database

The full electronic search strategies for all databases are described below.

PubMed

Search strategy

((“Rare Diseases”[Mesh] OR “Rare Diseases” OR “Orphan Disease” OR “Orphan Diseases” OR “Rare Disease” OR “Rare Conditions” OR “Rare Condition” OR “Rare Inborn Errors of Metabolism” OR “IEMs” OR “Inherited Metabolic Diseases” OR “22q11.2 Deletion Syndrome” OR “DiGeorge Syndrome” OR “Absence of Corpus Callosum” OR “Agenesis of Corpus Callosum” OR “Hypoplasia Of The Corpus Callosum” OR “Acromegaly” OR “Porphyria” OR “Porphyrias” OR “Postural Orthostatic Tachycardia Syndrome” OR “POTS” OR “Primary Adrenocortical Insufficiency” OR “Adrenal Insufficiency” OR “Addison Disease” OR “X-linked Adrenoleukodystrophy” OR “Adrenoleukodystrophy” OR “Alexander Disease” OR “Ataxia” OR “Ataxias” OR “Friedreich Ataxia” OR “Alport Syndrome” OR “Amyloidosis” OR “Amyotrophic Lateral Sclerosis” OR “Motor Neuron Disease” OR “Angelman Syndrome” OR “Ankylosing Spondylitis” OR “Anca Vasculitis” OR “Neutropenia” OR “Urea Cycle Disorder” OR “Arginase Deficiency” OR “Fibromuscular Dysplasia” OR “Atypical Haemolytic Uraemic Syndrome” OR “Atypical Hemolytic Uremic Syndrome” OR “Autoimmune Encephalitis” OR “Neuronal Ceroid Lipofuscinosis” OR “Batten Disease” OR “Becker Muscular Dystrophy” OR “Vestibular Disorder” OR “Bilateral Vestibular Loss” OR “Biotinidase Deficiency” OR “Pemphigoid” OR “Sarcoidosis” OR “Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy” OR “CADASIL” OR “Charcot-Marie-Tooth” OR “Congenital Adrenal Hyperplasia” OR “Congenital hyperinsulinism” OR “Congenital Hyperinsulinemic Hypoglycemia” OR “Cystic Fibrosis” OR “Dermatomyositis” OR “Inclusion Body Myositis” OR “Polymyositis” OR “Desmoid Tumor” OR “Scleroderma” OR “Systemic Sclerosis” OR “Dravet Syndrome” OR “Duchenne Muscular Dystrophy” OR “Epidermolysis Bullosa” OR “Erdheim Chester Disease” OR “Fabry” OR “Familial Chylomicronaemia Syndrome” OR “Familial Chylomicronemia Syndrome” OR “Familial Hypercholesterolemia” OR “Homozygous Hypercholesterolemia” OR “Fragile X” OR “Gaucher” OR “Myasthenia gravis” OR “Generalized Lymphatic Anomaly” OR “Gorham-Stout Disease” OR “Lymphangiomatosis” OR “Glycogen Storage Disease Type II” OR “Pompe” OR “Guillain-Barre Syndrome” OR “Haemophilia” OR “Hereditary Angioedema” OR “Ichthyosis” OR “Hereditary Spastic Paraplegia” OR “Hunter Syndrome” OR “Mucopolysaccharidosis type 2” OR “Mucopolysaccharidosis type II” OR “Huntington Disease” OR “Ehlers-Danlos Syndrome” OR “Hurler Syndrome” OR “Mucopolysaccharidosis Type 1” OR “Mucopolysaccharidosis Type I” OR “Hypoparathyroidism” OR “Hypophosphatasia” OR “Idiopathic Hypogonadotropic Hypogonadism” OR “Kallmann Syndrome” OR “Idiopathic Pulmonary Arterial Hypertension” OR “Idiopathic Pulmonary Hypertension” OR “Idiopathic Thrombocytopenia Purpura” OR “Idiopathic Pulmonary Fibrosis” OR “Kennedy Disease” OR “Spinal and Bulbar Muscular Atrophy” OR “Spinal Muscular Atrophy” OR “Congenital Muscular Dystrophy” OR “Lipodystrophy” OR “Long Chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency” OR “LCHAD” OR “Lymphangioleiomyomatosis” OR “Marfan Syndrome” OR “Mastocytosis” OR “Mccune-Albright Syndrome” OR “Methylmalonic Acidemia” OR “Carnitine deficiency” OR “Medium Chain Acyl-CoA Dehydrogenase Deficiency” OR “MCAD” OR “Mitochondrial Metabolism Disorder” OR “Mucopolysaccharidosis Type VI” OR “Mucopolysaccharidosis type VII” OR " Mucopolysaccharidosis type 4 A” OR “Mucopolysaccharidosis Type IV A” OR “Morquio” OR “Multifocal Motor Neuropathy” OR “Glutaric Acidemia” OR “Multiple Acyl-CoA Dehydrogenase Deficiency” OR “Multiple Sclerosis” OR “Multiple Sulfatase Deficiency” OR “Lysosomal Storage Disorder” OR “Multiple System Atrophy” OR “Myasthenia Gravis” OR “Myotonic Dystrophy” OR “X-Linked Myotubular Myopathy” OR “Myotubular Myopathy” OR “Idiopathic Hypersomnia” OR “Primary Hypersomnia” OR “Narcolepsy” OR “Neurofibromatosis 1” OR “Neurofibromatosis type 1” OR “Neuromyelitis Optica” OR “Niemann-Pick Disease type C” OR “Nontuberculous Mycobacteria” OR “Noonan Syndrome” OR “Ohtahara Syndrome” OR “Stxbp1 Encephalopathy With Epilepsy” OR “Osteogenesis Imperfecta” OR “Paraneoplastic Pemphigus” OR “Pemphigus Vulgaris” OR “Paroxysmal Nocturnal Hemoglobinuria” OR “Phelan-Mcdermid Syndrome” OR “22Q13” OR “Phenylketonuria” OR “Pompe” OR “Prader-Willi Syndrome” OR “Primary Biliary Cholangitis” OR “Primary Immunodeficiency” OR “Primary Lymphedema” OR “Dystonia” OR “Progressive Familial Intrahepatic Cholestasis” OR “Qt Syndrome” OR “Pseudo Hurler Polydystrophy” OR “Mucolipidosis” OR “Retinitis Pigmentosa” OR “Mucopolysaccharidosis III” OR “Sanfilippo Syndrome” OR “Sickle Cell Disease” OR “Peroxisomal Biogenesis Disorder” OR “Zellweger Spectrum Disorder” OR “Hyperphenylalaninemia” OR “Tetrahydrobiopterin Deficiency” OR “Tuberous Sclerosis Complex” OR “Turner Syndrome” OR “Leukodystrophy” OR “Williams Syndrome” OR “Wilson Disease” OR “Hypohidrotic Ectodermal Dysplasia”) AND (“Pharmacists”(Mesh) OR “Pharmacists”[Title/Abstract] OR “Pharmacist”[Title/Abstract] OR “Community Pharmacy Services”[Mesh] OR “Community Pharmacy Services”[Title/Abstract] OR “Community Pharmacy Service”[Title/Abstract] OR “Clinical Pharmacy Services”[Title/Abstract] OR “Clinical Pharmacy Service”[Title/Abstract] OR “Pharmacy”[Mesh] OR “Pharmacy”[Title/Abstract] OR “Pharmacies”[Title/Abstract] OR “Pharmacies”[Mesh] OR “Pharmaceutical Services”[Mesh] OR “Pharmaceutical Services”[Title/Abstract] OR “Pharmaceutical Service”[Title/Abstract] OR “Professional Pharmacy Service”[Title/Abstract] OR “Evidence-Based Pharmacy Practice”[Mesh] OR “Evidence-Based Pharmacy Practice”[Title/Abstract] OR “Specialty Pharmacy Service”[Title/Abstract] OR “Specialty Pharmacy Services”[Title/Abstract]))

Cumulative Index to Nursing and Allied Health

Search strategy

AB ((“Rare Diseases” OR “Orphan Disease” OR “Orphan Diseases” OR “Rare Disease” OR “Rare Conditions” OR “Rare Condition” OR “Rare Inborn Errors of Metabolism” OR “IEMs” OR “Inherited Metabolic Diseases” OR “22q11.2 Deletion Syndrome” OR “DiGeorge Syndrome” OR “Absence of Corpus Callosum” OR “Agenesis of Corpus Callosum” OR “Hypoplasia Of The Corpus Callosum” OR “Acromegaly” OR “Porphyria” OR “Porphyrias” OR “Postural Orthostatic Tachycardia Syndrome” OR “POTS” OR “Primary Adrenocortical Insufficiency” OR “Adrenal Insufficiency” OR “Addison Disease” OR “X-linked Adrenoleukodystrophy” OR “Adrenoleukodystrophy” OR “Alexander Disease” OR “Ataxia” OR “Ataxias” OR “Friedreich Ataxia” OR “Alport Syndrome” OR “Amyloidosis” OR “Amyotrophic Lateral Sclerosis” OR “Motor Neuron Disease” OR “Angelman Syndrome” OR “Ankylosing Spondylitis” OR “Anca Vasculitis” OR “Neutropenia” OR “Urea Cycle Disorder” OR “Arginase Deficiency” OR “Fibromuscular Dysplasia” OR “Atypical Haemolytic Uraemic Syndrome” OR “Atypical Hemolytic Uremic Syndrome” OR “Autoimmune Encephalitis” OR “Neuronal Ceroid Lipofuscinosis” OR “Batten Disease” OR “Becker Muscular Dystrophy” OR “Vestibular Disorder” OR “Bilateral Vestibular Loss” OR “Biotinidase Deficiency” OR “Pemphigoid” OR “Sarcoidosis” OR “Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy” OR “CADASIL” OR “Charcot-Marie-Tooth” OR “Congenital Adrenal Hyperplasia” OR “Congenital hyperinsulinism” OR “Congenital Hyperinsulinemic Hypoglycemia” OR “Cystic Fibrosis” OR “Dermatomyositis” OR “Inclusion Body Myositis” OR “Polymyositis” OR “Desmoid Tumor” OR “Scleroderma” OR “Systemic Sclerosis” OR “Dravet Syndrome” OR “Duchenne Muscular Dystrophy” OR “Epidermolysis Bullosa” OR “Erdheim Chester Disease” OR “Fabry” OR “Familial Chylomicronaemia Syndrome” OR “Familial Chylomicronemia Syndrome” OR “Familial Hypercholesterolemia” OR “Homozygous Hypercholesterolemia” OR “Fragile X” OR “Gaucher” OR “Myasthenia gravis” OR “Generalized Lymphatic Anomaly” OR “Gorham-Stout Disease” OR “Lymphangiomatosis” OR “Glycogen Storage Disease Type II” OR “Pompe” OR “Guillain-Barre Syndrome” OR “Haemophilia” OR “Hereditary Angioedema” OR “Ichthyosis” OR “Hereditary Spastic Paraplegia” OR “Hunter Syndrome” OR “Mucopolysaccharidosis type 2” OR “Mucopolysaccharidosis type II” OR “Huntington Disease” OR “Ehlers-Danlos Syndrome” OR “Hurler Syndrome” OR “Mucopolysaccharidosis Type 1” OR “Mucopolysaccharidosis Type I” OR “Hypoparathyroidism” OR “Hypophosphatasia” OR “Idiopathic Hypogonadotropic Hypogonadism” OR “Kallmann Syndrome” OR “Idiopathic Pulmonary Arterial Hypertension” OR “Idiopathic Pulmonary Hypertension” OR “Idiopathic Thrombocytopenia Purpura” OR “Idiopathic Pulmonary Fibrosis” OR “Kennedy Disease” OR “Spinal and Bulbar Muscular Atrophy” OR “Spinal Muscular Atrophy” OR “Congenital Muscular Dystrophy” OR “Lipodystrophy” OR “Long Chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency” OR “LCHAD” OR “Lymphangioleiomyomatosis” OR “Marfan Syndrome” OR “Mastocytosis” OR “Mccune-Albright Syndrome” OR “Methylmalonic Acidemia” OR “Carnitine deficiency” OR “Medium Chain Acyl-CoA Dehydrogenase Deficiency” OR “MCAD” OR “Mitochondrial Metabolism Disorder” OR “Mucopolysaccharidosis Type VI” OR “Mucopolysaccharidosis type VII” OR " Mucopolysaccharidosis type 4 A” OR “Mucopolysaccharidosis Type IV A” OR “Morquio” OR “Multifocal Motor Neuropathy” OR “Glutaric Acidemia” OR “Multiple Acyl-CoA Dehydrogenase Deficiency” OR “Multiple Sclerosis” OR “Multiple Sulfatase Deficiency” OR “Lysosomal Storage Disorder” OR “Multiple System Atrophy” OR “Myasthenia Gravis” OR “Myotonic Dystrophy” OR “X-Linked Myotubular Myopathy” OR “Myotubular Myopathy” OR “Idiopathic Hypersomnia” OR “Primary Hypersomnia” OR “Narcolepsy” OR “Neurofibromatosis 1” OR “Neurofibromatosis type 1” OR “Neuromyelitis Optica” OR “Niemann-Pick Disease type C” OR “Nontuberculous Mycobacteria” OR “Noonan Syndrome” OR “Ohtahara Syndrome” OR “Stxbp1 Encephalopathy With Epilepsy” OR “Osteogenesis Imperfecta” OR “Paraneoplastic Pemphigus” OR “Pemphigus Vulgaris” OR “Paroxysmal Nocturnal Hemoglobinuria” OR “Phelan-Mcdermid Syndrome” OR “22Q13” OR “Phenylketonuria” OR “Pompe” OR “Prader-Willi Syndrome” OR “Primary Biliary Cholangitis” OR “Primary Immunodeficiency” OR “Primary Lymphedema” OR “Dystonia” OR “Progressive Familial Intrahepatic Cholestasis” OR “Qt Syndrome” OR “Pseudo Hurler Polydystrophy” OR “Mucolipidosis” OR “Retinitis Pigmentosa” OR “Mucopolysaccharidosis III” OR “Sanfilippo Syndrome” OR “Sickle Cell Disease” OR “Peroxisomal Biogenesis Disorder” OR “Zellweger Spectrum Disorder” OR “Hyperphenylalaninemia” OR “Tetrahydrobiopterin Deficiency” OR “Tuberous Sclerosis Complex” OR “Turner Syndrome” OR “Leukodystrophy” OR “Williams Syndrome” OR “Wilson Disease” OR “Hypohidrotic Ectodermal Dysplasia”) AND (“Pharmacists” OR “Pharmacist” OR “Community Pharmacy Services” OR “Community Pharmacy Service” OR “Clinical Pharmacy Services” OR “Clinical Pharmacy Service” OR “Pharmacy” OR “Pharmacies” OR “Pharmaceutical Services” OR “Pharmaceutical Service” OR “Professional Pharmacy Service” OR “Evidence-Based Pharmacy Practice” OR “Specialty Pharmacy Service” OR “Specialty Pharmacy Services”))

Scopus

Search strategy

TITLE-ABS-KEY (((“Rare Diseases” OR “Rare Diseases” OR “Orphan Disease” OR “Orphan Diseases” OR “Rare Disease” OR “Rare Conditions” OR “Rare Condition” OR “Rare Inborn Errors of Metabolism” OR “IEMs” OR “Inherited Metabolic Diseases” OR “22q11.2 Deletion Syndrome” OR “DiGeorge Syndrome” OR “Absence of Corpus Callosum” OR “Agenesis of Corpus Callosum” OR “Hypoplasia Of The Corpus Callosum” OR “Acromegaly” OR “Porphyria” OR “Porphyrias” OR “Postural Orthostatic Tachycardia Syndrome” OR “POTS” OR “Primary Adrenocortical Insufficiency” OR “Adrenal Insufficiency” OR “Addison Disease” OR “X-linked Adrenoleukodystrophy” OR “Adrenoleukodystrophy” OR “Alexander Disease” OR “Ataxia” OR “Ataxias” OR “Friedreich Ataxia” OR “Alport Syndrome” OR “Amyloidosis” OR “Amyotrophic Lateral Sclerosis” OR “Motor Neuron Disease” OR “Angelman Syndrome” OR “Ankylosing Spondylitis” OR “Anca Vasculitis” OR “Neutropenia” OR “Urea Cycle Disorder” OR “Arginase Deficiency” OR “Fibromuscular Dysplasia” OR “Atypical Haemolytic Uraemic Syndrome” OR “Atypical Hemolytic Uremic Syndrome” OR “Autoimmune Encephalitis” OR “Neuronal Ceroid Lipofuscinosis” OR “Batten Disease” OR “Becker Muscular Dystrophy” OR “Vestibular Disorder” OR “Bilateral Vestibular Loss” OR “Biotinidase Deficiency” OR “Pemphigoid” OR “Sarcoidosis” OR “Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy” OR “CADASIL” OR “Charcot-Marie-Tooth” OR “Congenital Adrenal Hyperplasia” OR “Congenital hyperinsulinism” OR “Congenital Hyperinsulinemic Hypoglycemia” OR “Cystic Fibrosis” OR “Dermatomyositis” OR “Inclusion Body Myositis” OR “Polymyositis” OR “Desmoid Tumor” OR “Scleroderma” OR “Systemic Sclerosis” OR “Dravet Syndrome” OR “Duchenne Muscular Dystrophy” OR “Epidermolysis Bullosa” OR “Erdheim Chester Disease” OR “Fabry” OR “Familial Chylomicronaemia Syndrome” OR “Familial Chylomicronemia Syndrome” OR “Familial Hypercholesterolemia” OR “Homozygous Hypercholesterolemia” OR “Fragile X” OR “Gaucher” OR “Myasthenia gravis” OR “Generalized Lymphatic Anomaly” OR “Gorham-Stout Disease” OR “Lymphangiomatosis” OR “Glycogen Storage Disease Type II” OR “Pompe” OR “Guillain-Barre Syndrome” OR “Haemophilia” OR “Hereditary Angioedema” OR “Ichthyosis” OR “Hereditary Spastic Paraplegia” OR “Hunter Syndrome” OR “Mucopolysaccharidosis type 2” OR “Mucopolysaccharidosis type II” OR “Huntington Disease” OR “Ehlers-Danlos Syndrome” OR “Hurler Syndrome” OR “Mucopolysaccharidosis Type 1” OR “Mucopolysaccharidosis Type I” OR “Hypoparathyroidism” OR “Hypophosphatasia” OR “Idiopathic Hypogonadotropic Hypogonadism” OR “Kallmann Syndrome” OR “Idiopathic Pulmonary Arterial Hypertension” OR “Idiopathic Pulmonary Hypertension” OR “Idiopathic Thrombocytopenia Purpura” OR “Idiopathic Pulmonary Fibrosis” OR “Kennedy Disease” OR “Spinal and Bulbar Muscular Atrophy” OR “Spinal Muscular Atrophy” OR “Congenital Muscular Dystrophy” OR “Lipodystrophy” OR “Long Chain 3-hydroxyacyl-CoA Dehydrogenase Deficiency” OR “LCHAD” OR “Lymphangioleiomyomatosis” OR “Marfan Syndrome” OR “Mastocytosis” OR “Mccune-Albright Syndrome” OR “Methylmalonic Acidemia” OR “Carnitine deficiency” OR “Medium Chain Acyl-CoA Dehydrogenase Deficiency” OR “MCAD” OR “Mitochondrial Metabolism Disorder” OR “Mucopolysaccharidosis Type VI” OR “Mucopolysaccharidosis type VII” OR " Mucopolysaccharidosis type 4 A” OR “Mucopolysaccharidosis Type IV A” OR “Morquio” OR “Multifocal Motor Neuropathy” OR “Glutaric Acidemia” OR “Multiple Acyl-CoA Dehydrogenase Deficiency” OR “Multiple Sclerosis” OR “Multiple Sulfatase Deficiency” OR “Lysosomal Storage Disorder” OR “Multiple System Atrophy” OR “Myasthenia Gravis” OR “Myotonic Dystrophy” OR “X-Linked Myotubular Myopathy” OR “Myotubular Myopathy” OR “Idiopathic Hypersomnia” OR “Primary Hypersomnia” OR “Narcolepsy” OR “Neurofibromatosis 1” OR “Neurofibromatosis type 1” OR “Neuromyelitis Optica” OR “Niemann-Pick Disease type C” OR “Nontuberculous Mycobacteria” OR “Noonan Syndrome” OR “Ohtahara Syndrome” OR “Stxbp1 Encephalopathy With Epilepsy” OR “Osteogenesis Imperfecta” OR “Paraneoplastic Pemphigus” OR “Pemphigus Vulgaris” OR “Paroxysmal Nocturnal Hemoglobinuria” OR “Phelan-Mcdermid Syndrome” OR “22Q13” OR “Phenylketonuria” OR “Pompe” OR “Prader-Willi Syndrome” OR “Primary Biliary Cholangitis” OR “Primary Immunodeficiency” OR “Primary Lymphedema” OR “Dystonia” OR “Progressive Familial Intrahepatic Cholestasis” OR “Qt Syndrome” OR “Pseudo Hurler Polydystrophy” OR “Mucolipidosis” OR “Retinitis Pigmentosa” OR “Mucopolysaccharidosis III” OR “Sanfilippo Syndrome” OR “Sickle Cell Disease” OR “Peroxisomal Biogenesis Disorder” OR “Zellweger Spectrum Disorder” OR “Hyperphenylalaninemia” OR “Tetrahydrobiopterin Deficiency” OR “Tuberous Sclerosis Complex” OR “Turner Syndrome” OR “Leukodystrophy” OR “Williams Syndrome” OR “Wilson Disease” OR “Hypohidrotic Ectodermal Dysplasia”) AND (“Pharmacists” OR “Pharmacist” OR “Community Pharmacy Services” OR “Community Pharmacy Service” OR “Clinical Pharmacy Services” OR “Clinical Pharmacy Service” OR “Pharmacy” OR “Pharmacies” OR “Pharmaceutical Services” OR “Pharmaceutical Service” OR “Professional Pharmacy Service” OR “Evidence-Based Pharmacy Practice” OR “Specialty Pharmacy Service” OR “Specialty Pharmacy Services”))) AND (EXCLUDE (DOCTYPE, “bk”)) AND (EXCLUDE (DOCTYPE, “cp”) OR EXCLUDE (DOCTYPE, “ch”) OR EXCLUDE (DOCTYPE, “cr”))

Inclusion criteria

Research participants

Studies including patients with rare diseases and their demographics (gender, age, race, sex, etc) will be considered.

Types of studies

In this scoping review, experimental and quasi-experimental study designs including randomised controlled trials, non-randomised controlled trials, analytical observational studies with prospective and retrospective cohort designs, case-control studies and analytical cross-sectional studies will be considered for inclusion. Descriptive observational study designs including case series, individual case reports and qualitative studies will also be considered.

Types of interventions

Studies that explore the role of pharmacists in clinical services, either independently or as part of a multidisciplinary team, in pharmacies, health centres, and hospitals will be considered. It will be included studies that address pharmaceutical services aimed at promote the access to medicines, prevention and resolution of problems related to pharmacotherapy, use of medicines and obtaining results related to improving the quality of life of patients with rare diseases.

Outcomes

All outcomes from studies that meet the above inclusion criteria will be included in the review. Such outcomes could include (both quantitative and qualitative) clinical, humanistic or economic outcomes.

Exclusion criteria

Studies will be excluded if: articles without abstracts or full text available in the database; abstracts published in congresses; studies in poster format; book chapters; studies with no outcomes directly associated with pharmaceutical services; medicines clinical trials; studies related to diagnostic methods or drug development; comparison of the therapeutic effect of medicines or pricing.

Screening process

All retrieved studies will be exported to the Mendeley reference manager where duplicates will be removed. Study selection will be performed independently by two reviewers. Articles that meet the inclusion criteria will be reviewed in two stages. In the first stage, titles and abstracts will be reviewed, while the full texts will be reviewed in the second stage. The reasons for excluding sources that do not meet the inclusion criteria will be recorded and reported in the review. Any disagreements between reviewers in data extraction will be resolved by discussion with a third reviewer.

The references of the included articles will be evaluated so that relevant articles which may not have been retrieved in the search stage can be identified. Regular meetings will be held by the authors to achieve a consensus on the evidence.

No assessments of the articles’ quality will be made, as the purpose of this scoping review is to synthesise and describe the coverage of the evidence.

Data extraction

The instrument will be pilot tested with three studies by the researchers for preliminary data extraction. Data extraction will be performed independently by two reviewers. Any discrepancies will be resolved by discussion with a third reviewer.

The information to be extracted will be related to:

• Study characteristics: authors; publication date; type of study; and year of the investigation.

• Pharmaceutical intervention: pharmacy practice setting; intervention type; description of the intervention; and duration of the study.

• Population characteristics: geographical location of the study; sample size; demographic characteristics (age, sex, race); participant characteristics (patient, parents or caregivers, healthcare professionals); rare disease(s) addressed; and comparison group.

• Pharmaceutical intervention: from the framework for medicine management described in European Cystic Fibrosis Society Standards,¹⁵ the pharmaceutical clinical services will be categorised in: the provision of medicines, medication reconciliation; prescription monitoring; identification of adverse medicines reactions; improving adherence to treatment; educating and counselling patients and careers.

• Outcomes: the relevant health outcomes of the pharmaceutical services for patients with rare diseases will be reported:

  • Clinical impact of intervention: refer to the influence of the pharmaceutical services in optimising pharmacological treatment.

  • Humanistic outcomes: refer to improvement in quality of life and patient satisfaction.

  • Economic outcomes: refer to the reduction of medical expenses.

Patient and public involvement

The design of this scoping review protocol did not involve patients. The evidence reviews will consider the experiences of patients and/or their caregivers described in the literature, in order to answer the research question.

Presentation of the results

Initially, a flow chart of the data obtained at each stage of the review will be presented, including:

• total number of articles retrieved from the databases based on the search strategies adopted;

• total number of articles after duplicates are removed;

• total number of articles included and excluded after the title and abstract review;

• total number of articles included and excluded (and the reasons for exclusion) after full-text review;

• total number of articles obtained from the screening of reference lists;

• total number of articles that will be used for data extraction.

The data extracted from the studies included in this review will be presented in figures or tables. A systematised table will be developed covering pharmaceutical activities and their impact on the treatment of patients with rare diseases. The results from these current pieces of evidence will be summarised using descriptive statistics. They will be accompanied by a narrative synthesis that will address the information on the studies, participants, interventions for each type of disease and outcomes.

Ethics and dissemination

Primary data will not be collected in this study and formal ethical approval is not required.

The findings of this study will be disseminated through peer-reviewed publications and conference presentations. The findings will also be disseminated through relevant mailing lists and social media platforms.

This study can also be used to clarify future research efforts to address current evidence gaps in the field.

Perspectives

This scoping review has the potential to present a list of rare diseases and pharmaceutical services drawn from the experience of five countries (Brazil, China, the USA, the UK and Ireland), which can be used by health services as a basis for search and screening in their territories. It has the potential to help shape public policies regarding pharmaceutical services, not only for the countries mentioned but for all those who are seeking to implement interprofessional and comprehensive care for rare diseases. It may also point out opportunities to implement new healthcare approaches to better meet the needs of people with rare diseases, broaden the scope and effectiveness of pharmaceutical services and professionals, and obtain better clinical, humanistic and economic outcomes in the treatment to the patients.

Furthermore, this review will be useful to identify gaps in the training of pharmacists and healthcare teams, providing evidence for education, training development and opportunities for future research.

Ethics statements

Patient consent for publication

Not applicable.

Ethics approval

Not applicable.