Biologicals, defined as products of which the active substance is produced by or extracted from a biological source, represent an important and growing part of the therapeutic arsenal.¹ In the United States, the first biological, recombinant insulin, was approved in October 1982.² Since then, more than 250 biologicals, including recombinant (blood) products, monoclonal antibody−based products, and recombinant vaccines have been approved by regulatory authorities.³ Between 2003 and 2006, biologicals represented 24% and 22% of all new chemical entities approved by the US and EU regulatory authorities, respectively.⁴ Sales of biotech products in the United States showed an annual growth rate of 20% between 2001 and 2006 compared with 6% to 8% in the pharmaceutical market.⁵

Summary: Purpose:  In low‐ and middle‐income countries (LMICs), a large proportion of people with epilepsy do not receive treatment. An analysis of the availability, price, and affordability of antiepileptic drugs (AEDs) was conducted to evaluate whether these factors contribute to the treatment gap.Methods:  Data for five AEDs (phenytoin, carbamazepine, valproic acid, phenobarbital, and diazepam) were obtained from facility‐based surveys conducted in 46 countries using the World Health Organization/Health Action International (WHO/HAI) methodology. Outcome measures were percentage availability, ratios of local prices to international reference prices, and number of days’ wages needed by the lowest‐paid unskilled government worker to purchase treatment. Prices were adjusted for inflation/deflation and purchasing power parity.Key Findings:  The average availability of generic AEDs in the public sector was <50% for all medicines except diazepam injection. Private sector availability of generic oral AEDs ranged from 42.2% for phenytoin to 69.6% for phenobarbital. Public sector patient prices for generic carbamazepine and phenytoin were 4.95 and 17.50 times higher than international reference prices, respectively, whereas private sector patient prices were 11.27 and 24.77 times higher, respectively. For both medicines, originator brand prices were about 30 times higher. The highest prices were observed in the lowest income countries. The lowest‐paid government worker would need wages from 1–2.6 days’ to purchase a month’s supply of phenytoin, whereas carbamazepine would cost 2.7–16.2 days’ wages. Despite its widespread use in LMICs, WHO/HAI survey data for phenobarbital was only available from a small number of countries.Significance:  In LMICs, availability and affordability of AEDs are poor and may be acting as a barrier to accessing treatment for epilepsy. Ensuring a consistent supply of AEDs at an affordable price should be a priority.

OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic drugs. They inactivate incretin hormones but also have many other effects throughout the body, among which are effects on the immune system. This might result in an increased infection risk. This study assessed the association between use of DPP-4 inhibitors and the reporting of infections. RESEARCH DESIGN AND METHODS: A nested case-control was conducted using VigiBase, the World Health Organization-Adverse Drug Reactions (WHO-ADR) database. The base cohort consisted of ADRs for antidiabetic drugs (Anatomical Therapeutic Chemical code A10). Cases were defined as ADRs of infection according to the Medical Dictionary for Regulatory Activities (MedDRA) classification system. All other ADRs were considered controls. Reporting odds ratios (RORs) were calculated to estimate the strength of the association between different classes of antidiabetic drugs and the reporting of infections. RESULTS: We identified 305,415 suspected ADRs involving antidiabetic drugs in 106,469 case reports, of which 8,083 involved DPP-4 inhibitors monotherapy. Overall, the reporting of infections was higher for patients using DPP-4 inhibitors compared with users of biguanides (ROR 2.3 [95% CI 1.9–2.7]). Reporting of upper respiratory tract infections (ROR 12.3 [95% CI 8.6–17.5]) was significantly associated with use of DPP-4 inhibitors. CONCLUSIONS: This study indicates an increased reporting of infections, in particular upper respiratory tract infections, for users of DPP-4 inhibitors compared with users of other antidiabetic drugs. However, the limitations of spontaneous reporting systems (e.g., underreporting, the Weber-effect, reporting bias) should be taken into account. Therefore, further research is needed to evaluate this suspicion and the underlying mechanism.

The World Health Organization (WHO) promotes the development of national Essential Medicines Lists (EMLs) in order to improve the availability and use of medicines considered essential within health care systems. However, despite over 3 decades of international efforts, studies show an inconsistent pattern in the availability of essential medicines. We evaluated and compared the availability of essential medicines, and medicines not included in national EMLs, at global and regional levels. Medicine availability in the public and private sector were calculated based on data obtained from national and provincial facility-based surveys undertaken in 23 countries using the WHO/HAI methodology. The medicines were grouped according to their inclusion (‘essential’) or exclusion (termed ‘non-essential’) in each country’s EML current at the time of the survey. Availability was calculated for originator brands, generics and any product type (originator brands or generics) and compared between the two groups. Results were aggregated by WHO regions, World Bank country income groups, a wealth inequality measure, and therapeutic groups. Across all sectors and any product type, the median availability of essential medicines was suboptimal at 61·5% (IQR 20·6%–86·7%) but significantly higher than non-essential medicines at 27·3% (IQR 3·6%–70·0%). The median availability of essential medicines was 40·0% in the public sector and 78·1% in the private sector; compared to 6·6% and 57·1% for non-essential medicines respectively. A reverse trend between national income level categories and the availability of essential medicines was identified in the public sector. EMLs have influenced the provision of medicines and have resulted in higher availability of essential medicines compared to non-essential medicines particularly in the public sector and in low and lower middle income countries. However, the availability of essential medicines, especially in the public sector does not ensure equitable access.

Many low- and middle-income countries (LMIC) are moving towards enforcing prescription-only access to antibiotics. This systematic literature review aims to assess the interventions used to enforce existing legislation prohibiting over-the-counter (OTC) sales of antibiotics in LMICs, their impact and examine the methods chosen for impact measurement including their strengths and weaknesses. Both PubMed and Embase were systematically searched for studies reporting on impact measurement in moving towards prescription only access to antibiotics in LMICs. The PRISMA methodological review framework was used to ensure systematic data collection and analysis of literature. Narrative data synthesis was used due to heterogeneity of study designs. In total, 15 studies were included that assessed policy impact in 10 different countries. Strategies employed to enforce regulations prohibiting OTC sales of systemic antibiotics included retention of prescriptions for antibiotics by pharmacies, government inspections, engaging pharmacists in the design of interventions, media campaigns for the general public and educational activities for health care workers. A variety of outcomes was used to assess the policy impact; changes in antimicrobial resistance rates, changes in levels of antibiotic use, changes in trends of antibiotic use, changes in OTC supply of antibiotics, and changes in reported practices and knowledge of pharmacists, medicine sellers and the general public. Differences in methodological approaches and outcome assessment made it difficult to compare the effectiveness of law enforcement activities. Most effective appeared to be multifaceted approaches that involved all stakeholders. Monitoring of the impact on total sales of antibiotics by means of an interrupted time series (ITS) analysis and analysis of pharmacies selling antibiotics OTC using mystery clients were the methodologically strongest designs used. The published literature describing activities to enforce prescription-only access to antibiotics in LMICs is sparse and offers limited guidance. Most likely to be effective are comprehensive multifaceted interventions targeting all stakeholders with regular reinforcement of messages. Policy evaluation should be planned as part of implementation to assess the impact and effectiveness of intervention strategies and to identify targets for further activities. Robust study designs such as ITS analyses and mystery client surveys should be used to monitor policy impact.