BackgroundIn Latin American countries over-the-counter (OTC) dispensing of antibiotics is common. In 2010, both Mexico and Brazil implemented policies to enforce existing laws of restricting consumption of antibiotics only to patients presenting a prescription. The objective of the present study is therefore to evaluate the impact of OTC restrictions (2010) on antibiotics consumption in Brazil and Mexico.Methods and FindingsRetail quarterly sales data in kilograms of oral and injectable antibiotics between January 2007 and June 2012 for Brazil and Mexico were obtained from IMS Health. The unit of analysis for antibiotics consumption was the defined daily dose per 1,000 inhabitants per day (DDD/TID) according to the WHO ATC classification system. Interrupted time series analysis was conducted using antihypertensives as reference group to account for changes occurring independently of the OTC restrictions directed at antibiotics. To reduce the effect of (a) seasonality and (b) autocorrelation, dummy variables and Prais-Winsten regression were used respectively.Between 2007 and 2012 total antibiotic usage increased in Brazil (from 5.7 to 8.5 DDD/TID, +49.3%) and decreased in Mexico (10.5 to 7.5 DDD/TID, −29.2%). Interrupted time series analysis showed a change in level of consumption of −1.35 DDD/TID (p<0.01) for Brazil and −1.17 DDD/TID (p<0.00) for Mexico. In Brazil the penicillins, sulfonamides and macrolides consumption had a decrease in level after the intervention of 0.64 DDD/TID (p = 0.02), 0.41 (p = 0.02) and 0.47 (p = 0.01) respectively. While in Mexico it was found that only penicillins and sulfonamides had significant changes in level of −0.86 DDD/TID (p<0.00) and −0.17 DDD/TID (p = 0.07).ConclusionsDespite different overall usage patterns of antibiotics in Brazil and Mexico, the effect of the OTC restrictions on antibiotics usage was similar. In Brazil the trend of increased usage of antibiotics was tempered after the OTC restrictions; in Mexico the trend of decreased usage was boosted.

Abstractobjectives To describe and evaluate policies implemented in Chile, Colombia, Venezuela and Mexico (1995-2009) to prohibit antibiotic OTC sales and explore limitations in available data.methods We searched and analysed legislation, grey literature and peer-reviewed publications on regulatory interventions and implementation strategies to enforce prohibition of OTC antibiotic sales. We also assessed the impact using private sector retail sales data of antibiotics studying changes in level and consumption trends before and after the policy change using segmented time series analysis. Finally, we assessed the completeness and data quality through an established checklist to test the suitability of the data for analysis of the interventions.

Background As antiretroviral treatment (ART) for HIV/AIDS is scaled-up globally, information on per-person costs is critical to improve efficiency in service delivery and maximize coverage and health impact. Objective To review studies on delivery unit costs for adult and pediatric ART provision per-patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. Methods Systematic review of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analyzed by country income level and cost component. All costs were standardized to 2009 US dollars. Results Analyses covered 29 eligible, comprehensive costing studies. In the base case, in low-income countries (LIC), median, ART cost per patient-year was $792 (mean: $839, range: $682-$1089); for lower-middle-income countries (LMIC), the median was $932 (mean: $1246, range: $156-$3904); and for upper-middle-income countries (UMIC) the median was $1454 (mean: $2783, range: $1230-$5667). ARV drugs were largest component of overall ART cost in all settings (62%, 50% and 47% in LIC, LMIC and UMIC respectively). Out of 26 ART studies, 14 report which drug regimes were used, and only one study explicitly reported second line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 19.5%) whereas it was personnel costs in UMIC (26%). Two studies specified the types of laboratory tests costed, and three studies specifically included above-facility-level personnel costs. Three studies reported detailed PMTCT costs, and two studies reported on pediatric ART. Conclusions There is a paucity of data on the full ART and PMTCT delivery unit costs, in particular for low-and middle-income countries. Heterogeneity in activities costed and insufficient detail regarding components included in the costing hampers standardization of unit cost measures. Evaluation of program-level unit costs would benefit from international guidance on standardized costing methods, and expenditure categories and definitions. Future work should help elucidate the sources for the large variations in delivery unit costs across settings with similar income and epidemiological characteristics.

Medicines were the most prevalent component of health expenditures in Mexico. We recommend improving access to health services and strengthening access to medicines to reduce high OOPE.

Objective: To estimate drug exposure, Proportion of Days Covered (PDC) and percentage of patients with PDC ≥ 80% from a cohort of atrial fibrillation patients initiating oral anticoagulant (OAC) treatment. We employed three different approaches to estimate PDC, using either data from prescription and dispensing (PD cohort) or two common designs based on dispensing information only, requiring at least one (D1) or at least two (D2) refills for inclusion in the cohorts. Finally, we assessed the impact of adherence on health outcomes according to each method.Methods: Population-based retrospective cohort of all patients with Non Valvular Atrial Fibrillation (NVAF), who were newly prescribed acenocoumarol, apixaban, dabigatran or rivaroxaban from November 2011 to December 2015 in the region of Valencia (Spain). Patients were followed for 12 months to assess adherence using three different approaches (PD, D1 and D2 cohorts). To analyze the relationship between adherence (PDC ≥ 80) defined according to each method of calculation and health outcomes (death for any cause, stroke or bleeding) Cox regression models were used. For the identification of clinical events patients were followed from the end of the adherence assessment period to the end of the available follow-up period.Results: PD cohort included all patients with an OAC prescription (n = 38,802), D1 cohort excluded fully non-adherent patients (n = 265) and D2 cohort also excluded patients without two refills separated by 180 days (n = 2,614). PDC ≥ 80% ranged from 94% in the PD cohort to 75% in the D1 cohort. Drug exposure among adherent (PDC ≥ 80%) and non-adherent (PDC < 80%) patients was different between cohorts. In adjusted analysis, high adherence was associated with a reduced risk of death [Hazard Ratio (HR): from 0.82 to 0.86] and (except in the PD cohort) the risk for ischemic stroke (HR: from 0.61 to 0.64) without increasing the risk of bleeding.Conclusion: Common approaches to assess adherence using measures based on days’ supply exclude groups of non-adherent patients and, also, misattribute periods of doctors’ discontinuation to patient non-adherence, misestimating adherence overall. Physician-initiated discontinuation is a major contributor to reduced OAC exposure. When using the PDC80 threshold, very different groups of patients may be classified as adherent or non-adherent depending on the method used for the calculation of days’ supply measures. High adherence and high exposure to OAC treatment in NVAF patients is associated with better health outcomes.

Global HIV control funding falls short of need. To maximize health outcomes, it is critical that national governments sustain reasonable commitments, and that international donor assistance be distributed according to country needs and funding gaps. We develop a country classification framework in terms of actual versus expected national domestic funding, considering resource needs and donor financing. With UNAIDS and World Bank data, we examine domestic and donor HIV program funding in relation to need in 84 low- and middle-income countries. We estimate expected domestic contributions per person living with HIV (PLWH) as a function of per capita income, relative size of the health sector, and per capita foreign debt service. Countries are categorized according to levels of actual versus expected domestic contributions, and resource gap. Compared to national resource needs (UNAIDS Investment Framework), we identify imbalances among countries in actual versus expected domestic and donor contributions: 17 countries, with relatively high HIV prevalence and GNI per capita, have domestic funding below expected (median per PLWH $143 and $376, respectively), yet total available funding including from donors would exceed the need ($368 and $305, respectively) if domestic contribution equaled expected. Conversely, 27 countries have actual domestic funding above the expected (medians $294 and $149) but total (domestic+donor) funding does not meet estimated need ($685 and $1,173). Across the 84 countries, in 2009, estimated resource need totaled $10.3 billion, actual domestic contributions $5.1 billion and actual donor contributions $3.7 billion. If domestic contributions would increase to the expected level in countries where the actual was below expected, total domestic contributions would increase to $7.4 billion, turning a funding gap of $1.5 billion into a surplus of $0.8 billion. Even with imperfect funding and resource-need data, the proposed country classification could help improve coherence and efficiency in domestic and international allocations.

Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THIS TOPIC?  Decentralized clinical trials (DCTs) have the possibility to improve clinical trial conduct. However, regulatory requirements and perceived low degree of regulatory acceptance may impact the implementation of DCTs. WHAT QUESTION DID THIS STUDY ADDRESS?  What are the opportunities and challenges for the authorization and implementation of DCTs in Europe from a regulators' perspective? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?  Regulators expect that DCTs will facilitate the recruitment of underserved patients. Data collected in DCTs are furthermore expected to be more representative of the realworld. However, concerns regarding investigator oversight and safety monitoring may challenge DCT implementation. Regulators suggested that further experience with DCTs can be exerted through hybrid clinical trials, combining decentralized and on-site activities. HOW MIGHT THIS CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE? This research helps progress the implementation of DCTs by providing insights into the opportunities and challenges for its implementation from a European regulator's perspective. The themes described in this research should be considered when designing a DCT and could help to educate regulators on DCTs.

The COVID-19 pandemic and the accompanying control measures have significantly affected clinical trial (CT) conduct and sponsors have needed to make rapid changes to their CT operations. As a result, regulatory guidance was pivotal during the initial phases of the pandemic. This study aimed to evaluate the regulatory readiness and guidance related to COVID-19 in the European Union (EU). The European Medicines Agency (EMA) and national competent authorities' (NCAs) websites were searched in September and October 2020 for guidances on the management of CTs during the pandemic published from January 2020 onward. "Regulatory readiness" was defined as the number of days from the first European COVID-19 case (January 24, 2020) to the first published guidance by the respective NCA. "Regulatory guidance" was evaluated by coding the guidances for the following predefined operational trial activities important for ongoing CTs: obtaining informed consent, participant information, clinic visits, home health visits, telemedicine visits, self-monitoring, investigational medicinal product (IMP) supply, IMP adherence monitoring, CT monitoring, documentation management, regulatory management, and safety management. Twenty-four of the 27 EU NCAs published country-specific guidance. The time from the first European COVID-19 case to the first published EMA guidance was 56 days and ranged from 47 to 66 days for the first national guidances. Guidance was provided most frequently for regulatory management (24/24), safety management (23/24), documentation management (22/24), and CT monitoring (22/24). The regulatory guidance provided during the pandemic, ensuring participant safety and data integrity, may now be the starting point to innovate future CT conduct.