Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

The socioeconomic burden of spinal muscular atrophy in Saudi Arabia: a cross-sectional pilot study.

Background: Spinal muscular atrophy (SMA) is a rare debilitating condition with a significant burden for patients and society. However, little is known about how it affects Saudi Arabia's population. The socioeconomic and medical characteristics of affected SMA patients and their caregivers are lacking. Purpose: This study aimed to describe the socioeconomic and medical characteristics of SMA patients and caregivers in Saudi Arabia. Patients and methods: A cross-sectional questionnaire-based study was conducted using snowball sampling. Assessment tools including EuroQol (EQ-5D-5L) and visual analog scale (EQ-VAS), Generalized Anxiety Disorder 7-item (GAD-7), Patient Health Questionnaire (PHQ-9), and Costs for Patients Questionnaire (CoPaQ) were used to assess the quality of life (QoL), anxiety, depression, and out-of-pocket expenditures. Results: Sixty-four caregivers of SMA patients participated. Type I patients had higher sibling concordance, ICU hospitalization, and mechanical support needs. Type III patients had better QoL. Type I patients' caregivers had higher depression scores. Type III patients' caregivers had higher out-of-pocket expenditures. Forty-eight percent received supportive care, while others received SMA approved therapies. Conclusion: SMA imposes a significant socioeconomic burden on patients and caregivers, requiring more attention from the healthcare system. Access to innovative therapies varied across SMA types. Pre-marital screening and early detection are crucial to reduce disease incidence and ensure timely treatment.

A Step Toward the Development of the First National Multi-Criteria Decision Analysis Framework to Support Healthcare Decision Making in Saudi Arabia.

OBJECTIVES: To assess the feasibility of implementing multi-criteria decision analysis (MCDA) and to select the criteria for preparing a national MCDA framework for health technology assessment of orphan drugs in the Kingdom of Saudi Arabia (KSA). METHODS: The study was conducted in 3 phases. In phase I, a targeted literature review was performed to gather relevant information on the implementation of MCDA in healthcare decision making. Phase II was a cross-sectional survey, conducted to obtain insights from different stakeholders and key opinion leaders on specific topics from the KSA perspective. Phase III included a round-table discussion involving experts to validate the results obtained in the phase II survey and further elaborate on specific requirements that may be critical for developing the first national MCDA framework in the KSA. RESULTS: All the key opinion leaders involved in the study acknowledged the importance of implementing MCDA in the KSA. The Ministry of Health was assigned the responsibility of chairing the MCDA decision process. The experts selected the quantitative, qualitative, and economic criteria to be considered for the MCDA framework. The stakeholders decided to initiate a pilot phase using the deliberative MCDA methodology for the assessment of orphan drugs based on the selected criteria for a period of 1 year and then reevaluate the need to adapt the pragmatic MCDA model. CONCLUSION: This article describes the novel initiative that examined the feasibility and process required for the development of the first MCDA framework in the KSA to support healthcare decision making.

Budget impact of introducing oral semaglutide to the public healthcare benefit package in Saudi Arabia.

BACKGROUND: The Kingdom of Saudi Arabia (KSA) has embarked on a Health Sector Transformation Program as part of the Kingdom's Vision 2030 initiatives with the facilitation of access to healthcare services for the millions in KSA with diabetes an essential part of the Program. Decision-making tools, such as budget impact models, are required to consider the addition of new medications like oral semaglutide that have multifaceted health benefits and address barriers related to therapeutic inertia to reduce diabetes-related complications. OBJECTIVE: To determine the financial impact of the introduction of oral semaglutide as a treatment option for people with type 2 diabetes mellitus (T2DM) in KSA. METHODS: From the public payer's perspective, the budget impact model estimates the costs before and after the introduction of oral semaglutide over a 5-year time horizon. The budget impact of introducing oral semaglutide (primary comparator) compared with three different classes of diabetes medicines: glucagon-like peptide-1 receptor agonists (GLP-1), sodium-glucose transport protein 2 inhibitors (SGLT 2i) and dipeptidyl peptidase 4 inhibitors (DDP-4i) have been calculated based on the projected market shares. The model includes the cost of care through the incorporation of health outcomes that have an impact on the national payer's budget in Saudi Riyals (SAR). RESULTS: The budget impact over the five-year time horizon indicates a medication cost increase (17,424,788 SAR), and cost offsets which include a difference in diabetes management costs (-3,625,287 SAR), CV complications costs (-810,733 SAR) and weight loss savings of 453,936 SAR. The cumulative total cost difference is 12,427,858 SAR (0.66%). CONCLUSION: The introduction of oral semaglutide 14 mg as a second-line treatment option after metformin is indicated as budget-neutral to slightly budget-inflating for the public pharmaceutical formulary of KSA. The price difference is offset by positive health outcomes and costs. This conclusion was confirmed through a probabilistic sensitivity analysis.

Obesity Burden and Impact of Weight Loss in Saudi Arabia: A Modelling Study.

BACKGROUND: Obesity and its complications are associated with morbidity, mortality and high economic cost in Saudi Arabia. Estimating this impact at the population level and potential benefits to be gained from obesity reduction is vital to underpin policy initiatives to prevent disease risks. METHODS: We combined data in an adapted version of the value of weight loss simulation model, to predict reductions in complication rates and cost savings achievable with 15% weight loss in Saudi Arabia over 10 years. To obtain model inputs, we conducted a systematic literature review (SLR) to identify data on the prevalence of obesity and its complications in Saudi Arabia, and surveyed specialist physicians and hospital administrators in public (governmental) and private healthcare sectors. We used combinations of age, sex, obesity and type 2 diabetes (T2D) rates in Saudi Arabia to sample a United Kingdom (UK) cohort, creating a synthetic Saudi Arabia cohort expected to be representative of the population. RESULTS: The synthetic Saudi Arabia cohort reflected expected comorbidity prevalences in the population, with a higher estimated prevalence of T2D, hypertension and dyslipidaemia than the UK cohort in all age groups. For 100,000 people with body mass index 30-50 kg/m2, it was estimated that 15% weight loss would lead to a 53.9% reduction in obstructive sleep apnoea, a 37.4% reduction in T2D and an 18.8% reduction in asthma. Estimated overall cost savings amounted to 1.026 billion Saudi Arabian Riyals; the largest contributors were reductions in T2D (30% of total cost savings for year 10), dyslipidaemia (26%) and hypertension (19%). CONCLUSIONS: Sustained weight loss could significantly alleviate the burden of obesity-related complications in Saudi Arabia. Adopting obesity reduction as a major policy aim, and ensuring access to support and treatment should form an important part of the transformation of the healthcare system, as set out under 'Vision 2030'.

The Impact of Obesity in Saudi Arabia: Healthcare Resource Use and Costs Associated with Obesity-Related Complications.

INTRODUCTION: Saudi Arabia has a high prevalence of obesity, which increases the risk of individuals experiencing multiple chronic complications. Only a few publications highlight the healthcare costs of obesity-related complications (ORCs) in Saudi Arabia. METHODS: A micro-costing approach was used to estimate the healthcare costs associated with 10 ORCs. Experienced clinicians in public and private practice across different geographical regions in Saudi Arabia were asked to estimate healthcare resource use associated with each ORC, and estimated unit costs were obtained from hospital administrators. Estimated overall annual costs per patient were calculated as a weighted average of separate public and private sector costs. RESULTS: Individuals in Saudi Arabia with any single ORC incurred overall average annual healthcare costs of 2165-7558 US dollars (USD). Heart failure, chronic kidney disease, dyslipidemia, and type 2 diabetes (T2D) were the most costly complications, mainly driven by monitoring and/or pharmacological treatment costs. In contrast, asthma, hypertension, and angina were the least costly complications. Costs in private healthcare were higher than in public healthcare; the largest differences (2359-2793 USD) were noted for dyslipidemia, T2D, and osteoarthritis, mainly explained by differences in pharmacological treatment costs. CONCLUSIONS: These data suggest that ORCs result in a considerable financial burden to the healthcare system, and highlight the substantial cost savings that could be achieved by preventing or delaying the occurrence of ORCs in Saudi Arabia.

Efficacy and Safety of Empagliflozin in Type 2 Diabetes Mellitus Saudi Patients as Add-On to Antidiabetic Therapy: A Prospective, Open-Label, Observational Study.

The Saudi Food and Drug Authority (SFDA) approved sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2018. The efficacy and safety of empagliflozin (EMPA) have been confirmed in the U.S., Europe, and Japan for patients with type 2 diabetes mellitus (T2DM); however, analogous evidence is lacking for Saudi T2DM patients. Therefore, the current study aimed to assess the efficacy and safety of EMPA in Saudi patients (n = 256) with T2DM. This is a 12-week prospective, open-label, observational study. Adult Saudi patients with T2DM who had not been treated with EMPA before enrolment were eligible. The exclusion criteria included T2DM patients less than 18 years of age, adults with type one diabetes, pregnant women, paediatric population. The results related to efficacy included a significant decrease in haemoglobin A1c (HbA1c) (adjusted mean difference −0.93% [95% confidence interval (CI) −0.32, −1.54]), significant improvements in fasting plasma glucose (FPG) (−2.28 mmol/L [95% CI −2.81, −1.75]), and a reduction in body weight (−0.874 kg [95% CI −4.36, −6.10]) following the administration of 25 mg of EMPA once daily as an add-on to ongoing antidiabetic therapy after 12 weeks. The primary safety endpoints were the change in the mean blood pressure (BP) values, which indicated significantly reduced systolic and diastolic BP (−3.85 mmHg [95% CI −6.81, −0.88] and −0.06 mmHg [95% CI −0.81, −0.88], respectively) and pulse rate (−1.18 [95% CI −0.79, −3.15]). In addition, kidney function was improved, with a significant reduction in the urine albumin/creatinine ratio (UACR) (−1.76 mg/g [95% CI −1.07, −34.25]) and a significant increase in the estimated glomerular filtration rate (eGFR) (3.54 mL/min/1.73 m2 [95% CI 2.78, 9.87]). Furthermore, EMPA reduced aminotransferases (ALT) in a pattern (reduction in ALT > AST). The adjusted mean difference in the change in ALT was −2.36 U/L [95% CI −1.031, −3.69], while it was −1.26 U/L [95% CI −0.3811, −2.357] for AST and −1.98 U/L [95% CI −0.44, −3.49] for GGT. Moreover, in the EMPA group, serum high-density lipoprotein (HDL) significantly increased (0.29 mmol/L [95% CI 0.74, 0.15]), whereas a nonsignificant increase was seen in low-density lipoprotein (LDL) (0.01 mmol/L [95% CI 0.19, 0.18]) along with a significant reduction in plasma triglyceride (TG) levels (−0.43 mmol/L [95% CI −0.31, −1.17]). Empagliflozin once daily is an efficacious and tolerable strategy for treating Saudi patients with insufficiently controlled T2DM as an add-on to ongoing antidiabetic therapy.

Real-World Impact of Switching From Insulin Glargine (Lantus®) to Basaglar® and Potential Cost Saving in a Large Public Healthcare System in Saudi Arabia.

Background: The advent of Basaglar®, which is a biosimilar insulin glargine formulation for Lantus® has brought hope that it will result in similar outcomes and lower costs. However, some health practitioners raised some concerns about the therapeutic equivalence of this new biosimilar. Therefore, we aimed to examine the clinical and financial impact of switching from Lantus® to Basaglar®. Methods: This was a single-center retrospective chart review study of adult patients (e.g., ≥18 years) with diabetes mellitus (DM) who were treated with insulin glargine (Lantus®) for at least 12 months and then switched to Basaglar® for another 12 months. The potential cost savings for the years 2018 to 2021 and the cost avoidance for 2022 were estimated using different conversion ratios between the two insulin glargine products (Basaglar® and Lantus®) and acquisition prices. Results: One-hundred patients with DM who were previously treated with Lantus® and switched to Basaglar® were retrospectively recruited. About two-thirds of the patients (68%) had type 2 DM, and the male and female patients were equally represented. The mean glycated hemoglobin (A1C) at baseline was 9, and the mean difference in the A1C levels before and after switching to Basaglar® was not significant (0.18, p-value = 0.503, 95% CI [-0.36-0.72]). Although the difference in the total daily insulin units between Lantus® and Basaglar® was not significant, the difference was leaning toward statistical significance despite the small sample size (-1.88, P-value = 0.25, 95% CI [-5.15-1.38]). Switching from Lantus® to Basaglar® could have led to significant cost savings that would range from approximately 1.77 to 23.7 million United States Dollars (USD) for the years 2018 to 2021 assuming an equal conversion ratio. However, those cost savings might not be realized if the switching to Basaglar® required higher daily insulin units, and the difference in the public tender acquisition price between Lantus® and Basaglar® is less than 15%. Conclusion: Basaglar® and potentially other biosimilar insulin glargine products can lead to significant cost savings without compromising the quality of care. However, their acquisition prices should be discounted.

The Impact of COVID-19 on Essential Medicines and Personal Protective Equipment Availability and Prices in Saudi Arabia.

This was a questionnaire-based cross-sectional study that explored the impact of the COVID-19 pandemic on the availability of essential medicine and personal protective equipment (PPE) in Saudi Arabia. Purposive sampling technique was used to recruit individuals working in the supply chain departments in different healthcare sectors in Saudi Arabia. One hundred and three pharmaceutical and medical supply chain employees participated in the study. Most of the participants (58.3%) were aged ≥35 years, male (65%), and pharmacists (92.2%). The majority of participants had at least two years of experience in supply chain (77.6%), worked in public hospitals (95.15%), and were mostly working at healthcare institutions located in Riyadh province (59.2%). Approximately 51% of the participants reported shortages of 10 or more essential drugs. Tocilizumab, hydroxychloroquine, lopinavir/ritonavir, ribavirin, dexamethasone, enoxaparin, interferon beta-1b, cisatracurium besylate, prednisolone, hydrocortisone, methimazole, and methylprednisolone were reported to be in shortage by at least 8% of the participants. Almost 70% of the participants reported that the pandemic did not significantly impact the prices of prescription drugs in shortage (e.g., ≥25%). Moreover, about 70% of the participants reported direct purchasing or procurement of drugs in shortage. Surgical masks, face shields, medical gowns, and N95 respirators were reported to be in short supply by 33% or more of the participants. Approximately 53% of the participants reported the prices of PPE in shortage had seen an increase by at least 25% during the pandemic. Although the COVID-19 pandemic has caused a significant disruption in the global pharmaceutical supply chain, its impact was largely manageable in Saudi healthcare institutions. This can be attributable to multiple reasons such as the effective exchange programs between hospitals and the drastic increase in public healthcare spending to ameliorate the negative impact of the pandemic on the healthcare sector.

Drug shortages in Saudi Arabia: Root causes and recommendations.

Drug shortages are a multifaceted problem that has been recurring in Saudi Arabia over the past decade with its significant negative impact on patient care. However, there is a dearth of evidence about possible domestic reasons, if any, behind this recurring problem. Recently, the Pharmacy Education Unit at King Saud University College of Pharmacy has called for a meeting with multiple stakeholders from academia, pharmaceutical care, pharmaceutical industry, purchasing and planning, and regulatory bodies to unveil the root domestic causes of the drug shortages in the Kingdom. Four major topics were used to guide the discussion in this meeting, including: current situation of drug shortages in Saudi Arabia, major factors contributing to drug shortages, challenges and obstacles to improve drug supply, and stakeholders' recommendations to manage drug shortages. The meeting was audio-recorded and transcribed into verbatim by five authors. The text was then reviewed and analyzed to identify different themes by the first and third authors. Multiple causes were identified and several recommendations were proposed. The main domestic causes of drug shortages that were explored in this study included poor medication supply chain management, lack of government regulation that mandates early notification of drug shortages, a government procurement policy that does not keep pace with the changes in the pharmaceutical market, low profit margins of some essential drugs, weak and ineffective law-violation penalties against pharmaceutical companies and licensed drug importers and distributors, and overdependence on drug imports. The participants have also proposed multiple recommendations to address drug shortages. Policy makers should consider these factors that contribute to drug shortages in Saudi Arabia as well as the recommendations when designing future initiatives and interventions to prevent drug shortages.