Journal of Pharmaceutical Research International

Background: To make reimbursement decisions for orphan medicines the regulators need robust evidences for their efficacy and safety provided by systematic reviews and meta-analyses.

The goal of the current study is to evaluate the efficacy and safety of orphan medicines included in the Positive Drug List (PDL) in Bulgaria through the application of meta-analysis.

Methods: Internet based literature search in scientific databases such as Pub Med, ClinicalTrials.gov, EU Clinical Trials Register for the identification of all published clinical trials with orphan medicines Idursulfase, Sapropterin and Pasireotide was performed. The technological Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram was applied to present the flow of information during the different stages of systematic review. A set of statistical methods available in statistical software MedCalc were used to perform meta-analysis and comparison of proportions for diseases’ specific clinical parameters and adverse reactions. The studies were filtered on the basis of eligibility criteria: A clinical focus; randomized or open-label studies with clearly presented outcome variables; equal or similar time horizon; sufficient data about safety and efficacy processed with reliable statistical approaches.

Results: Fixed effect was used in patients treated with Idursulfase who experienced urticaria (p = 0.3459, 6.81%, 95% CI 3,126-12,623) and serious adverse drug reactions (ADRs) (p=0.0619, 21.27%, 95% CI, 14,561 - 29,345) and in patients treated with Sapropterin who experienced ADRs (P = 0.2264, 29,237%, 95% CI 20,916-38,720). Random effect was taken into account for Pasireotide effectiveness data and the percent of patients with controlled levels of urinary free cortisol (UFC) was 44.81%, 95% CI (37,506 - 56,073), which proves the difference in the effects among different samples. The results from the heterogeneity test shows that random effect for the percent of Pasireotide treated patients with nausea (р=0,2675, 51,936%, 95% CI 40.401-63,32), hyperglycemia (p=0,0504, 43.268%, 95% CI 34.217-52.662) and diarrhea (p=0.3221,58,299%, 95% CI 46.658-69.299) must be applied.

Conclusions: The aggregated data on efficacy presented by meta-analysis could be used for the conduction of pharmacoeconomic analysis for the purposes of the assessment of orphan medicines efficiency.