ABSTRACT
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.
ABSTRACT
CONTEXT: Several international studies have described the epidemiology of pulmonary hypertension (PH). However, information about the incidence and prevalence of PH in Saudi Arabia is unknown. AIMS: To report cases of PH and compare the demographic and clinical characteristics of PH due to various causes in a Saudi population. METHODS: Newly diagnosed cases of PH [defined as mean pulmonary artery pressure >25 mmHg at right heart cauterization (RHC)] were prospectively collected at a single tertiary care hospital from January 2009 and June 2012. Detailed demographic and clinical data were collected at the time of diagnosis, along with hemodynamic parameters. RESULTS: Of the total 264 patients who underwent RHC, 112 were identified as having PH. The mean age at diagnosis was 55.8 ± 15.8 years, and there was a female preponderance of 72.3%. About 88 (78.6%) of the PH patients were native Saudis and 24 (21.4%) had other origins. Twelve PH patients (10.7%) were classified in group 1 (pulmonary arterial hypertension), 7 (6.2%) in group 2 (PH due to left heart disease), 73 (65.2%) in group 3 (PH due to lung disease), 4 (3.6%) in group 4 (chronic thromboembolic PH), and 16 (14.3%) in group 5 (PH due to multifactorial mechanisms). PH associated with diastolic dysfunction was noted in 28.6% of group 2 patients, 31.5% of group 3 patients, and 25% of group 5 patients. CONCLUSIONS: These results offer the first report of incident cases of PH across five groups in Saudi Arabia.
