Systematic literature review and meta-analysis on the epidemiology of methylmalonic acidemia (MMA) with a focus on MMA caused by methylmalonyl-CoA mutase (mut) deficiency.

Methylmalonic acidemia/aciduria (MMA) is a genetically heterogeneous group of inherited metabolic disorders biochemically characterized by the accumulation of methylmalonic acid. Isolated MMA is primarily caused by the deficiency of methylmalonyl-CoA mutase (MMA mut; EC 5.4.99.2). A systematic literature review and a meta-analysis were undertaken to assess and compile published epidemiological data on MMA with a focus on the MMA mut subtype (OMIM #251000). Of the 1114 identified records, 227 papers were assessed for eligibility in full text, 48 articles reported on disease epidemiology, and 39 articles were included into the quantitative synthesis. Implementation of newborn screening in various countries has allowed for the estimation of birth prevalence of MMA and its isolated form. Meta-analysis pooled point estimates of MMA (all types) detection rates were 0.79, 1.12, 1.22 and 6.04 per 100,000 newborns in Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. The detection rate of isolated MMA was < 1 per 100,000 newborns in all regions with the exception of MENA where it approached 6 per 100,000 newborns. Few studies published data on the epidemiology of MMA mut, therefore no meta-analysis could have been performed on this subtype. Most of the identified papers reported birth prevalence estimates below 1 per 100,000 newborns for MMA mut. The systematic literature review clearly demonstrates that MMA and its subtypes are ultra-rare disorders.

Systematic literature review and meta-analysis on the epidemiology of propionic acidemia.

Propionic acidemia (PA, OMIM #606054) is a serious, life-threatening, inherited, metabolic disorder caused by the deficiency of the mitochondrial enzyme propionyl-coenzyme A (CoA) carboxylase (EC 6.4.1.3). The primary objective of this study was to conduct a systematic literature review and meta-analysis on the epidemiology of PA. The literature search was performed covering Medline, Embase, Cochrane Database of Systematic Reviews, CRD Database, Academic Search Complete, CINAHL and PROSPERO databases. Websites of rare disease organizations were also searched for eligible studies. Of the 2338 identified records, 188 articles were assessed for eligibility in full text, 43 articles reported on disease epidemiology, and 31 studies were included into the quantitative synthesis. Due to the rarity of PA, broadly targeted population-based prevalence studies are not available. Nonetheless, implementation of newborn screening programs has allowed the estimation of the birth prevalence data of PA across multiple geographic regions. The pooled point estimates indicated detection rates of 0.29; 0.33; 0.33 and 4.24 in the Asia-Pacific, Europe, North America and the Middle East and North Africa (MENA) regions, respectively. Our systematic literature review and meta-analysis confirm that PA is an ultra-rare disorder, with similar detection rates across all regions with the exception of the MENA region where the disease, similar to other inherited metabolic disorders, is more frequent.

Epidemiology of Sanfilippo syndrome: results of a systematic literature review.

BACKGROUND: Sanfilippo syndrome (mucopolysaccharidosis [MPS] III subtypes A, B, C, and D) is a rare autosomal recessive inherited metabolic disorder that causes progressive neurocognitive degeneration. This systematic literature review was undertaken to compile and assess published epidemiological data, including various frequency measures and geographical variation on Sanfilippo syndrome. METHODS: The following databases were systematically searched for terms related to Sanfilippo syndrome epidemiology: Medline, Embase, Cochrane Database of Systematic Reviews, Academic Search Complete, Cumulative Index to Nursing and Allied Health Literature, and the Centre for Reviews and Dissemination. Qualitative synthesis of research findings was performed. RESULTS: Of 2794 publications found in the initial search, 116 were deemed eligible after title and abstract screening. Following full-text review, 46 papers were included in the qualitative synthesis. Results of this systematic literature review indicate that lifetime risk at birth ranges from 0.17-2.35 per 100,000 live births for all 4 subtypes of MPS III together, and from 0.00-1.62 per 100,000 live births for the most frequent subtype, MPS IIIA. CONCLUSION: All 4 subtypes of MPS III are exceptionally rare, but they each have devastating effects on children. Higher-quality epidemiological data are needed to appropriately target resources for disease research and management.

Policy objective of generic medicines from the investment perspective: The case of clopidogrel.

The objective of generic drug policies in most countries is defined from a disinvestment perspective: reduction in expenditures without compromising health outcomes. However, in countries with restricted access of patients to original patented drugs, the objective of generic drug policies can also be defined from an investment perspective: health gain by improved patient access without need for additional health budget. This study examines the investment aspect of generic medicines by analyzing clopidogrel utilization in European countries between 2004 and 2014 using multilevel panel data models. We find that clopidogrel consumption was strongly affected by affordability constraints before the generic entry around 2009, but this effect decayed by 2014. After controlling for other variables, utilization had a substantially larger trend increase in lower-income European countries than in the higher-income ones. Generic entry increased clopidogrel consumption only in lower- and average-income countries but not in the highest-income ones. An earlier generic entry was associated with a larger effect. The case of clopidogrel indicates that the entrance of generics may increase patient access to effective medicines, most notably in lower-income countries, thereby reducing inequalities between European patients. Policymakers should also consider this investment aspect of generic medicines when designing pharmaceutical policies.