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Choosing profile double-sampling designs for survival estimation with application to President's Emergency Plan for AIDS Relief evaluation.

ABSTRACT: Most studies that follow subjects over time are challenged by having some subjects who dropout. Double sampling is a design that selects and devotes resources to intensively pursue and find a subset of these dropouts, then uses data obtained from these to adjust naïve estimates, which are potentially biased by the dropout. Existing methods to estimate survival from double sampling assume a random sample. In limited-resource settings, however, generating accurate estimates using a minimum of resources is important. We propose using double-sampling designs that oversample certain profiles of dropouts as more efficient alternatives to random designs. First, we develop a framework to estimate the survival function under these profile double-sampling designs. We then derive the precision of these designs as a function of the rule for selecting different profiles, in order to identify more efficient designs. We illustrate using data from the United States President's Emergency Plan for AIDS Relief-funded HIV care and treatment program in western Kenya. Our results show why and how more efficient designs should oversample patients with shorter dropout times. Further, our work suggests generalizable practice for more efficient double-sampling designs, which can help maximize efficiency in resource-limited settings.

SUBMITTER: An MW

PROVIDER: S-EPMC4013226 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Choosing profile double-sampling designs for survival estimation with application to President's Emergency Plan for AIDS Relief evaluation.

An Ming-Wen MW Frangakis Constantine E CE Yiannoutsos Constantin T CT

Statistics in medicine 20140110 12

Most studies that follow subjects over time are challenged by having some subjects who dropout. Double sampling is a design that selects and devotes resources to intensively pursue and find a subset of these dropouts, then uses data obtained from these to adjust naïve estimates, which are potentially biased by the dropout. Existing methods to estimate survival from double sampling assume a random sample. In limited-resource settings, however, generating accurate estimates using a minimum of reso ...[more]

PMID: 24408038

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Project description:The US budget for global health funding, which was by far the largest of similar funding in the world, increased from US $1.3 billion in 2001 to more than US $10 billion in recent years. More than 54% of this funding was allocated to the Global Fund to Fight HIV/AIDS through the US President's Emergency Plan for AIDS Relief (PEPFAR) in Africa. However, recent studies indicate contradictory results regarding the effectiveness of PEPFAR. One by Bendavid, Holmes, Bhattacharya, and Miller shows positive effects of PEPFAR in reducing adult mortality in Africa, while another by Duber, Coates, Szekeras, Kaji, and Lewis finds that there are no significant differences in reducing adult mortality in countries that received PEPFAR funding vs countries that did not. Due to their potential impact on policy decisions regarding critical global health funding, we wanted to assess why the results are discrepant. To do this, we replicated the Bendavid study. The replication provides verification that the study replicable and that the analytic choices of the authors are robust to different assumptions or restrictions. This allows us to assess the different choices and data available to the two research groups and draw some conclusions about why the results may be different. Then, focusing on two of the prominently discrepant studies, i.e., the Bendavid study (1998-2008) and the Duber study (2000-2006), we establish why the two studies are in disagreement. We apply appropriate individual-level and country-level analytical methodology as used by Bendavid over the analytical time period used for the Duber study (2000-2006), which originally focused on nationally aggregated data and differed in some key focus countries. For our first objective, we replicated the original Bendavid study findings and our findings support their conclusion that between 1998-2008 all-cause mortality decreased significantly more (OR = 0.84, CI, 0.72-0.99) in countries that implemented PEPFAR. For our second objective (Bendavid's data and methodology applied to Duber's study period), we found reduction in all cause adult mortality to be borderline insignificant (OR = 0.87 CI, 0.75-1.01, p = 0.06), most possibly reflecting the abbreviated fewer number of events and sample size over a shorter period. Therefore, our overall analyses are consistent with the conclusion of positive impact of the PEPFAR program in reducing adult mortality. We believe that the discrepancy observed in the original studies mainly a reflection of shortcomings in the analytical approach necessitated by the Duber study's nationally aggregated dataset or "may reflect a lack of data quality" in the Duber study (Duber, et al. 2010).

Project description:Support of human immunodeficiency virus (HIV) and tuberculosis (TB) testing and treatment supported by President's Emergency Plan for AIDS Relief (PEPFAR) in Africa requires immense quantities of tests and medications. We sought to use central pharmacy supply data of Mozambique's rural Zambézia Province (2017 population ≈5.11 million persons; ≈12.6% adult HIV prevalence in 2016) to examine shortages, stockouts, and trends in availability. Using stock surveillance for 60 weeks in 2014-2015, we assessed availability of 36 medications [4 classes: adult antiretroviral (ARV) medications, pediatric ARVs, anti-TB medications, and antibiotics] and diagnostic test kits (2 rapid tests for HIV; 1 each for malaria and syphilis). We contrasted these to 2018-2019 data. We modeled pharmacy data using ordinal logistic regression, characterizing weekly product availability in four categories: good, adequate, shortage, or complete stockout. We found 166 (7.7%) stockouts and 150 (6.9%) shortages among 2,160 weekly records. Earlier calendar time was associated with reduced medication supplies (p < .001). Certain medication/test kit classes were associated with reduced supply (p < .001). We found an interaction between time and medication class on the odds of reduced supply (p < .001). Pediatric ARVs had a 17.4 (95% confidence interval: 8.8-34.4) times higher odds of reduced medication supply compared with adult ARVs at study midpoint. Trends comparing the first and last weeks showed adult ARVs having 67% and pediatric having 71% lower odds of reduced supplies. Only adult ARV shortages improved amid growing demand. Data from 2018 to 2019 suggest continuing inventory management challenges. Monitoring of drug (especially pediatric) and test kit shortages is vital to ensure quality improvement to guarantee adequate supplies to enable patients and care providers to achieve sustained viral suppression. A central Mozambican drug repository in the nation's second largest Province continues to experience drug and rapid test kit stockouts.

Project description:ImportanceFrom 2004 to 2014, the US President's Emergency Plan for AIDS Relief (PEPFAR) invested more than $248 000 000 in the prevention of mother-to-child transmission (PMTCT) of HIV in Kenya. Concurrently, child mortality in Kenya decreased by half.ObjectiveTo identify the extent to which the decrease in child mortality in Kenya is associated with PEPFAR funding for PMTCT of HIV.Design, setting, and participantsThis population-based survey study conducted in Kenya estimated the association between annual per capita PEPFAR funding for PMTCT (annual PCF) and cumulative per capita PEPFAR funding for PMTCT (cumulative PCF), extracted using 2004-2014 country operational reports as well as individual-level health outcomes, extracted from the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys and the 2007 and 2012 Kenya AIDS Indicator Surveys. The study included children of female respondents to the 2003, 2008-2009, and 2014 Kenya Demographic and Health Surveys who were born 1 to 60 months (for neonatal mortality) or 12 to 60 months (for infant mortality) before the survey, as well as female respondents who had recently given birth and reported on HIV testing during antenatal care (ANC) during the 2007-2014 surveys. Results were adjusted for year, province, and survey respondent characteristics. Statistical analysis was performed from July 8, 2016, to December 10, 2018.Main outcomes and measuresNeonatal mortality was defined as death within the first month of life and infant mortality was defined as death within the first year of life. HIV testing during ANC was defined as receiving counseling on PMTCT, undergoing an HIV test, and receiving test results during ANC.ResultsThe analysis included 33 181 neonates (16 870 boys), 26 876 infants (13 679 boys), and 20 775 mothers (mean [SD] age, 28.0 [6.7] years). PEPFAR funding was not associated with neonatal mortality. A $0.33 increase in annual PCF, corresponding to the difference between the 75th and 25th (interquartile range) percentiles of funding, was significantly associated with a 16% (95% CI, 4%-27%) reduction in infant mortality after a 1-year lag. A 14% to 16% reduction persisted after 2- and 3-year lags, and comparable reductions were observed for unlagged and 1-year lagged cumulative PCF. An increase of 1 interquartile range in cumulative PCF was associated with a 7% (95% CI, 3%-11%) increase in HIV testing during ANC, which intensified with subsequent lags. Between 2004 and 2014, sustained funding levels of $0.33 annual PCF could have averted 118 039 to 273 924 infant deaths.Conclusions and relevanceEvidence from publicly available data suggests that PEPFAR's PMTCT funding was associated with a reduction in infant mortality and an increase in HIV testing during ANC in Kenya. The full outcome of funding may not be realized until several years after allocation.

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Choosing profile double-sampling designs for survival estimation with application to President's Emergency Plan for AIDS Relief evaluation.

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Choosing profile double-sampling designs for survival estimation with application to President's Emergency Plan for AIDS Relief evaluation.

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