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.

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.

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).

Unit costs for delivery of antiretroviral treatment and prevention of mother-to-child transmission of HIV: a systematic review for low- and middle-income countries.

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 to maximize coverage and health impact. The objective of this study was to review studies on unit costs for delivery of adult and paediatric ART 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. A systematic review was conducted 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 analysed by country-income level and cost component. All costs were standardized to $US, year 2009 values. Several sensitivity analyses were conducted. Analyses covered 29 eligible, comprehensive, costing studies. In the base case, in low-income countries (LIC), median ART cost per patient-year was $US792 (mean: 839, range: 682-1089); for lower-middle-income countries (LMIC), the median was $US932 (mean: 1246, range: 156-3904); and, for upper-middle-income countries (UMIC), the median was $US1454 (mean: 2783, range: 1230-5667). ARV drugs were the largest component of overall ART costs in all settings (64%, 50% and 47% in LIC, LMIC and UMIC, respectively). Of 26 ART studies, 14 reported the drug regimes used, and only one study explicitly reported second-line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 20%), and personnel costs in UMIC (26%). Two ART 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 three studies reported on paediatric ART. There is a paucity of data on the full unit costs for delivery of ART and PMTCT, particularly for LIC 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 programme-level unit costs would benefit from international guidance on standardized costing methods, and expenditure categories and definitions. Future work should help elucidate the sources of the large variations in delivery unit costs across settings with similar income and epidemiological characteristics.

Ambulatory health service users' experience of waiting time and expenditure and factors associated with the perception of low quality of care in Mexico.

BACKGROUND: A principal reason for low use of public health care services is the perception of inferior quality of care. Studying health service user (HSU) experiences with their care and their perception of health service quality is critical to understanding health service utilization. The aim of this study was to define reference points for some aspects of health care quality and to analyze which HSU experiences resulted in perceptions of overall low quality of care. METHODS: Data from the National Health Survey 2006 were used to compare the experiences of HSUs with their ambulatory care at Ministry of Health and affiliated institutions (MOH), social security institutions (SSI) and private institutions (PrivI). Reference points of quality of care related to waiting time and expenditure were defined for each of the three types of institutions by analyzing HSU experiences rated as 'acceptable'. A multivariable logistic regression model was used to identify the principal factors associated with the general perception of low quality of care. RESULTS: A total of 11,959 HSUs were included in the analysis, of whom 37.6% (n = 4,500) HSUs received care at MOH facilities; 31.2% (n = 3,730) used SSI and 31.2% (n = 3,729) PrivI. An estimated travel and waiting time of 10 minutes respectively was rated as acceptable by HSUs from all institutions. The differences between the waiting time rated as acceptable and the actual waiting time were the largest for SSI (30 min) in comparison to MoH (20 min) and PrivI (5 min) users. The principal factors associated with an overall perception of low quality of care are type of institution (OR 4.36; 95% CI 2.95-6.44), waiting time (OR 3.20; 95% CI 2.35-4.35), improvement of health after consultation (OR 2.93; CI 2.29-3.76) and consultation length of less than 20 minutes (2.03; 95% CI 1.60-2.57). CONCLUSIONS: The reference points derived by the HSUs' own ratings are useful in identifying where quality improvements are required. Prioritizing the reduction of waiting times and improving health status improvement after consultation would increase overall quality of care ratings.