Opportunities and Challenges for Decentralized Clinical Trial Approaches: European Health Technology Assessment Perspective.

OBJECTIVES: Decentralized clinical trial (DCT) approaches are clinical trials in which some or all trial activities take place closer to participants' proximities instead of a traditional investigative site. Data from DCTs may be used for clinical and economic evaluations by health technology assessment (HTA) bodies to support reimbursement decision making. This study aimed to explore the opportunities and challenges for DCT approaches from an HTA perspective by interviewing representatives from European HTA bodies. METHODS: We conducted semistructured interviews with 25 European HTA representatives between September 2022 and February 2023, and transcripts were analyzed after thematic analysis. RESULTS: Two main themes were identified from the data relating to (1) DCT approaches in HTA and (2) trial-level acceptance and relevance. Experience with assessing DCTs was limited and a variety of knowledge about DCTs was observed. The respondents recognized the opportunity of DCTs to reduce recall bias when participant-reported outcome data can be collected more frequently and conveniently from home. Concerns were expressed about the data quality when participants become responsible for data collection. Despite this challenge, the respondents recognized the potential of DCTs to increase the generalizability of results because data can be collected in a setting reflective of the everyday situation potentially from a more diverse participant group. CONCLUSIONS: DCTs could generate relevant results for HTA decision making when data are collected in a real-world setting from a diverse participant group. Increased awareness of the opportunities and challenges could help HTA assessors in their appraisal of DCT approaches.

Unintended impact of pharmacovigilance regulatory interventions: A systematic review.

AIMS: Studies assessing the impact of pharmacovigilance regulatory interventions often focus on the expected (or intended) outcomes, while any possible unintended impact may be overlooked. The update of the Good Pharmacovigilance Practice guideline in 2017 elaborated on impact assessment, emphasizing the need also to assess possible unintended impact. This systematic literature review investigated how often the unintended impact of regulatory interventions was considered in publications of studies investigating pharmacovigilance regulatory interventions in Europe. METHODS: We conducted a systematic review of the literature on MEDLINE and EMBASE from 1 January 2012 to 28 February 2022 to identify publications that investigated the impact of regulatory interventions in Europe. The primary outcome of the study was the number of publications reporting assessments of unintended impact. In addition, we studied the characteristics of these publications, including the type of outcomes assessed, the analytical methods applied and the type of data used. RESULTS: In total, 96 publications were included in the analysis. The unintended impact of pharmacovigilance regulatory interventions was investigated in 23 of 96 publications (24%). The drug classes most frequently studied in the publications assessing unintended impact of regulatory interventions were oral glucose-lowering drugs (n = 6, 26%), opioids (n = 4, 17%), antidepressants (n = 4, 17%) and antipsychotics (n = 3, 13%). The reported methods to assess the unintended impact were interrupted time series (n = 10, 43%) and descriptive statistics with or without significance testing (n = 2 [9%] and n = 9 [39%], respectively). The outcomes selected for unintended impact assessments included the use of other drugs (n = 16, 70%), health outcomes (n = 8, 35%) and behavioural changes (n = 4, 17%). Most of the publications reported on the use of electronic health record databases (n = 13, 57%) or claims databases (n = 13, 57%), while registries were used in 4 publications (17%). CONCLUSION: The unintended impact of pharmacovigilance regulatory interventions was reported in only a quarter of identified publications. There was no apparent increase in attention to unintended impact assessments after the update of the Good Pharmacovigilance Practice guidelines.

Direct-to-participant investigational medicinal product supply in clinical trials in Europe: Exploring the experiences of sponsors, site staff and couriers.

AIMS: Insights into the current practice of direct-to-participant (DtP) supply of investigational medicinal product (IMP) in the context of clinical trials conducted in Europe are needed, as regulations are unharmonized. This study is set out to explore how DtP IMP supply has been employed in Europe and what the advantages and disadvantages and barriers and facilitators of its implementation are. METHODS: We conducted semi-structured interviews with representatives from sponsor companies, courier services and site study staff involved in the IMP dispensing and delivery process in Europe. Interviews were conducted between May and November 2021, and data were analysed following thematic analysis. RESULTS: Sixteen respondents participated in one of the 12 interviews. Respondents had experience with different models of DtP IMP supply including shipment from the investigative site, a central pharmacy (a depot under the control of a pharmacist) and a local pharmacy-aiming to reduce trial participation burden. The respondents indicated that investigative site-to-participant shipment is not affected by regulatory barriers, but could burden site staff. Shipment from central locations was considered most efficient, but possible regulatory barriers related to maintaining participants' privacy and investigator oversight were identified. The respondents indicated that the involvement of local pharmacies to dispense IMP can be considered when the IMP is authorized. CONCLUSIONS: Several DtP IMP supply models are implemented in clinical trials conducted in Europe. In this study, three main DtP IMP models were identified, which can be referenced when describing these approaches for regulatory approval.

Decentralised, patient-centric, site-less, virtual, and digital clinical trials? From confusion to consensus.

There is increasing interest in clinical trials that use technologies and other innovative operational approaches to organise trial activities around trial participants instead of investigator sites. A range of terms has been introduced to refer to this operational clinical trial model, including virtual, digital, remote, and decentralised clinical trials (DCTs). However, this lack of standardised terminology can cause confusion over what a particular trial model entails and for what purposes it can be used, hampering discussions by stakeholders on its acceptability and suitability. Here, we review the different terms described in the scientific literature, advocate the consistent use of a unified term, 'decentralised clinical trial,' and provide a detailed definition of this term.

Which decentralised trial activities are reported in clinical trial protocols of drug trials initiated in 2019-2020? A cross-sectional study in ClinicalTrials.gov.

OBJECTIVES: Decentralised clinical trial activities-such as participant recruitment via social media, data collection through wearables and direct-to-participant investigational medicinal product (IMP) supply-have the potential to change the way clinical trials (CTs) are conducted and with that to reduce the participation burden and improve generalisability. In this study, we investigated the decentralised and on-site conduct of trial activities as reported in CT protocols with a trial start date in 2019 or 2020. DESIGN: We ascertained the decentralised and on-site conduct for the following operational trial activities: participant outreach, prescreening, screening, obtaining informed consent, asynchronous communication, participant training, IMP supply, IMP adherence monitoring, CT monitoring, staff training and data collection. Results were compared for the public versus private sponsors, regions involved, trial phases and four time periods (the first and second half of 2019 and 2020, respectively). SETTING: Phases 2, 3 and 4 clinical drug trial protocols with a trial start date in 2019 or 2020 available from ClinicalTrials.gov. OUTCOME MEASURES: The occurrence of decentralised and on-site conduct of the predefined trial activities reported in CT protocols. RESULTS: For all trial activities, on-site conduct was more frequently reported than decentralised conduct. Decentralised conduct of the individual trial activities was reported in less than 25.6% of the 254 included protocols, except for decentralised data collection, which was reported in 68.9% of the protocols. More specifically, 81.9% of the phase 3 protocols reported decentralised data collection, compared with 73.3% and 47.0% of the phase 2 and 4 protocols, respectively. For several activities, including prescreening, screening and consenting, upward trends in reporting decentralised conduct were visible over time. CONCLUSIONS: Decentralised methods are used in CTs, mainly for data collection, but less frequently for other activities. Sharing best practices and a detailed description in protocols can drive the adoption of decentralised methods.

Ethics review of decentralized clinical trials (DCTs): Results of a mock ethics review.

Decentralized clinical trials (DCTs) can be a valuable addition to the clinical trial landscape. However, the practice of DCTs is dependent on a regulatory system designed for conventional (site-based) trials. This study provides insight into the ethics review of DCTs. A 'mock ethics review' was performed in which members of European ethics committees (ECs) and national competent authorities (NCAs) discussed and reviewed a DCT protocol. Respondents expressed hesitancy toward DCTs and focused on potential risks and burdens. We advise to address these aspects explicitly when submitting a DCT protocol. We propose that both the benefits and risks of DCTs should be carefully monitored to advance the review and practice of this innovative approach to ethically optimize drug development.

Opportunities and Challenges for Decentralized Clinical Trials: European Regulators' Perspective.

Decentralized clinical trials (DCTs) have the potential to improve accessibility, diversity, and retention in clinical trials by moving trial activities to participants' homes and local surroundings. In this study, we conducted semi-structured interviews with 20 European regulators to identify regulatory challenges and opportunities for the implementation of DCTs in the European Union. The key opportunities for DCTs that were recognized by regulators include a reduced participation burden, which could facilitate the participation of underserved patients. In addition, regulators indicated that data collected in DCTs are expected to be more representative of the real world. Key challenges recognized by regulators for DCTs include concerns regarding investigator oversight and participants' safety when physical examinations and face-to-face contact are limited. To facilitate future learning, hybrid clinical trials with both on-site and decentralized elements are proposed by the respondents.

Data sources for drug utilization research in Latin American countries-A cross-national study: DASDUR-LATAM study.

PURPOSE: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region. METHODS: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed. RESULTS: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data. CONCLUSIONS: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration.

COVID-19 and the Emerging Regulatory Guidance for Ongoing Clinical Trials in the European Union.

The coronavirus disease 2019 (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.

Clinical outcomes of nonvitamin K oral anticoagulants and acenocoumarol for stroke prevention in contemporary practice: A population-based propensity-weighted cohort study.

AIMS: Acenocoumarol is a vitamin-K antagonist (VKA) primarily used in certain countries (e.g. India, Netherlands, Spain). The half-life of acenocoumarol is similar to that of non-VKA oral anticoagulants (NOAC), unlike warfarin, and this could affect comparative effectiveness and safety (CES). However, data on CES for NOAC come almost exclusively from studies using warfarin as the comparator. We aimed to assess outcomes of NOAC and acenocoumarol in people with non-valvular atrial fibrillation (NVAF) in real-world clinical practice. METHODS: This is a population-based retrospective cohort study. All new users of oral anticoagulants from November 2011 to December 2015 with NVAF were included (n = 41,560). Data were obtained by linking several health electronic records of the Valencia region, Spain. Incidence rates were estimated. We used the inverse probability of treatment weighted Cox analysis to control for indication bias when assessing the risk of effectiveness and safety outcomes for each NOAC compared with acenocoumarol. Several sensitivity analyses were performed. RESULTS: We did not find differences in the risk of mortality, ischaemic stroke or any gastrointestinal bleeding. However, we did find a decreased risk of intracranial haemorrhage for dabigatran (HR: 0.34, 95% CI 0.20-0.56) and rivaroxaban (HR: 0.55, 95% CI 0.35-0.85) as compared to acenocoumarol. In subanalyses, apixaban showed a higher risk of ischaemic stroke in high-risk persons (≥75 years and CHA2DS2-VASC score ≥ 2). CONCLUSIONS: No differences in clinical outcomes were found between NOAC and acenocoumarol overall, although dabigatran and rivaroxaban showed a lower risk of intracranial haemorrhage. Findings on the potential inferiority of specific NOAC in high-risk subgroups should be studied further.

Estimating Adherence Based on Prescription or Dispensation Information: Impact on Thresholds and Outcomes. A Real-World Study With Atrial Fibrillation Patients Treated With Oral Anticoagulants in Spain.

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.

Impact of the introduction of mandatory generic substitution in South Africa: private sector sales of generic and originator medicines for chronic diseases.

OBJECTIVE: To assess the impact of mandatory offer of generic substitution, introduced in South Africa in May 2003, on private sector sales of generic and originator medicines for chronic diseases. METHODS: Private sector sales data (June 2001 to May 2005) were obtained from IMS Health for proton pump inhibitors (PPIs; ATC code A02BC), HMG-CoA reductase inhibitors (statins; C10AA), dihydropyridine calcium antagonists (C08CA), angiotensin-converting enzyme inhibitors (ACE-I; C09AA) and selective serotonin reuptake inhibitors (SSRIs; N06AB). Monthly sales were expressed as defined daily doses per 1000 insured population per month (DDD/TIM). Interrupted time-series models were used to estimate the changes in slope and level of medicines use after the policy change. ARIMA models were used to correct for autocorrelation and stationarity. RESULTS: Only the SSRIs saw a significant rise in level of generic utilisation (0.2 DDD/TIM; P < 0.001) and a fall in originator usage (-0.1 DDD/TIM; P < 0.001) after the policy change. Utilisation of generic PPIs fell (level 0.06 DDD/TIM, P = 0.048; slope 0.01 DDD/TIM, P = 0.043), but utilisation of originator products also grew (level 0.05 DDD/TIM, P < 0.001; slope 0.003, P = 0.001). Generic calcium antagonists and ACE-I showed an increase in slope (0.01 DDD/TIM, P = 0.016; 0.02 DDD/TIM, P < 0.001), while the originators showed a decrease in slope (-0.003 DDD/TIM, P = 0.046; -0.01 DDD/TIM, P < 0.001). There were insufficient data on generic statin use before the policy change to allow for analysis. CONCLUSION: The mandatory offer of generic substitution appeared to have had a quantifiable effect on utilisation patterns in the 2 years after May 2003. Managed care interventions that were already in place before the intervention may have blunted the extent of the changes seen in this period. Generic policies are an important enabling provision for cost-containment efforts. However, decisions taken outside of official policy may anticipate or differ from that policy, with important consequences.

Effects of over-the-counter sales restriction of antibiotics on substitution with medicines for symptoms relief of cold in Mexico and Brazil: time series analysis.

We evaluated changes in the use of non-steroidal anti-inflammatory drugs (NSAIDs), non-opioid analgesics and cough and cold medicines and its relation with the use of antibiotics after the over-the-counter (OTC) antibiotic sales restrictions in Mexico and Brazil. IMS Health provided retail quarterly data from the private sectors in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. Data of each active substance of antibiotics, easily accessible medicines perceived as antibiotics substitutes (cough and cold medicines, analgesics and NSAIDs-the latter two being combined in the analyses), and medicines to control for external factors that can affect the medicines usage trend (antihypertensives) were converted from kilograms to defined daily doses per 1000 inhabitants days (DDD/TID). Interrupted time series were used to estimate changes in level of medicines use at the intervention point and slope after the regulation. The Gregory-Hansen cointegration test was used to explore the relation between the use of antibiotics and perceived substitutes. After the regulation in Mexico NSAIDs-analgesics usage level increased by 1.1 DDD/TID with a slope increase of 0.2 DDD/TID per quarter and the cough and cold medicines usage level increased by 0.4 DDD/TID. In Brazil NSAIDs-analgesics usage level increased by 1.9 DDD/TID, and cough and cold medicines did not change. In the two countries, NSAIDs-analgesics usage changes were related with antibiotic usage changes; in Mexico cough and cold medicines usage changes had a relation with the antibiotics usage changes. These results showed a substitution effect on the use of other medicines, especially NSAIDs and analgesics, after reinforcement of OTC antibiotics sales restrictions. These regulations aimed to improve the antibiotics use and as a consequence reduce antimicrobial resistance; however, this type of policies should be comprehensive and take into account the potential substitution effects on the use of other medicines.

Seasonal variation in penicillin use in Mexico and Brazil: analysis of the impact of over-the-counter restrictions.

During 2010, Mexico and Brazil implemented policies to enforce existing laws of restricting over-the-counter sales of antibiotics. We determined if the enforcement led to more appropriate antibiotic use by measuring changes in seasonal variation of penicillin use. We used retail quarterly sales data in defined daily doses per 1,000 inhabitant-days (DDD/TID) from IMS Health from the private sector in Mexico and Brazil from the first quarter of 2007 to the first quarter of 2013. This database contains information on volume of antibiotics sold in retail pharmacies using information from wholesalers. We used interrupted time-series models controlling for external factors with the use of antihypertensives with interaction terms to assess changes in trend, level, and variation in use between quarters for total penicillin use and by active substance. The most used penicillin was amoxicillin, followed by amoxicillin-clavulanic acid and ampicillin (minimal use in Brazil). Before the restrictions, the seasonal variation in penicillin use was 1.1 DDD/TID in Mexico and 0.8 DDD/TID in Brazil. In Mexico, we estimated a significant decrease in the seasonal variation of 0.4 DDD/TID after the restriction, mainly due to changes in seasonal variation of amoxicillin and ampicillin. In Brazil, the seasonal variation did not change significantly, overall and in the breakdown by individual active substances. For Mexico, inappropriate penicillin use may have diminished after the restrictions were enforced. For Brazil, increasing use and no change in seasonal variation suggest that further efforts are needed to reduce inappropriate penicillin use.

Impact of over-the-counter restrictions on antibiotic consumption in Brazil and Mexico.

BACKGROUND: In 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 FINDINGS: Retail 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). CONCLUSIONS: Despite 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.

Financing HIV programming: how much should low- and middle-income countries and their donors pay?

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.

Heterogeneous effects of health insurance on out-of-pocket expenditure on medicines in Mexico.

OBJECTIVE: Given the importance of health insurance for financing medicines and recent policy changes designed to reduce health-related out-of-pocket expenditure (OOPE) in Mexico, our study examined and analyzed the effect of health insurance on the probability and amount of OOPE for medicines and the proportion spent from household available expenditure (AE) funds. METHODS: We conducted a cross-sectional analysis by using the Mexican National Household Survey of Income and Expenditures for 2008. Households were grouped according to household medical insurance type (Social Security, Seguro Popular, mixed, or no affiliation). OOPE for medicines and health costs, and the probability of occurrence, were estimated with linear regression models; subsequently, the proportion of health expenditures from AE was calculated. The Heckman selection procedure was used to correct for self-selection of health expenditure; a propensity score matching procedure and an alternative procedure using instrumental variables were used to correct for heterogeneity between households with and without Seguro Popular. RESULTS: OOPE in medicines account for 66% of the total health expenditures and 5% of the AE. Households with health insurance had a lower probability of OOPE for medicines than their comparison groups. There was heterogeneity in the health insurance effect on the proportion of OOPE for medicines out of the AE, with a reduction of 1.7% for households with Social Security, 1.4% for mixed affiliation, but no difference between Seguro Popular and matched households without insurance. CONCLUSION: 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.

Allocating scarce financial resources for HIV treatment: benchmarking prices of antiretroviral medicines in Latin America.

Public sector price analyses of antiretroviral (ARV) medicines can provide relevant information to detect ARV procurement procedures that do not obtain competitive market prices. Price benchmarks provide a useful tool for programme managers and policy makers to support such planning and policy measures. The aim of the study was to develop regional and global price benchmarks which can be used to analyse public-sector price variability of ARVs in low- and middle-income countries using the procurement prices of Latin America and the Caribbean (LAC) countries in 2008 as an example. We used the Global Price Reporting Mechanism (GPRM) data base, provided by the World Health Organization (WHO), for 13 LAC countries' ARV procurements to analyse the procurement prices of four first-line and three second-line ARV combinations in 2008. First, a cross-sectional analysis was conducted to compare ARV combination prices. Second, four different price 'benchmarks' were created and we estimated the additional number of patients who could have been treated in each country if the ARV combinations studied were purchased at the various reference ('benchmark') prices. Large price variations exist for first- and second-line ARV combinations between countries in the LAC region. Most countries in the LAC region could be treating between 1.17 and 3.8 times more patients if procurement prices were closer to the lowest regional generic price. For all second-line combinations, a price closer to the lowest regional innovator prices or to the global median transaction price for lower-middle-income countries would also result in treating up to nearly five times more patients. Some rational allocation of financial resources due, in part, to price benchmarking and careful planning by policy makers and programme managers can assist a country in negotiating lower ARV procurement prices and should form part of a sustainable procurement policy.

Costs of interventions for AIDS orphans and vulnerable children.

OBJECTIVE: To review the published and grey literature for information regarding the costs and cost-effectiveness of interventions aimed at improving the welfare of orphans and vulnerable children owing to HIV/AIDS in low- and middle-income countries. METHOD: We carried out a search of the peer-reviewed literature through PubMed, EconLit, and Web of Science for the period January 2000 to December 2010. We also extensively reviewed the grey literature through generalized web searches and consultations with experts and searches of the web pages of the main organizations active in providing services to orphans and vulnerable children (OVC). The search yielded 216 articles; cross-sectional or longitudinal studies and articles that did not address specific interventions were not considered. The remaining 21 articles were categorized by domain and by type of intervention strategy. RESULTS: All studies reviewed were carried out in sub-Saharan Africa. All outcomes are expressed as cost per child per year (in 2010 USD). Foster care estimates range from $614 to $1921. Educational support for primary school ranged from $30 to $75. Health interventions that would ensure child survival can be delivered for about $55. CONCLUSION: More research is needed to improve planning and delivery of interventions for OVC. The paucity of cost and cost-effectiveness data reflects the limited number of effectiveness studies. Nevertheless, this systematic literature review shows evidence that suggests that in the area of housing, foster care appears to be more cost effective than institutional care (orphanages).