PLoS Medicine最新文献

Background: High incidence rates of HIV, sexually transmitted infections (STIs), and teenage pregnancy are major challenges facing South Africa. The role of socio-economic factors in driving these incidence rates is complex, with high socio-economic status protecting against some risk behaviours (condomless sex, early sexual debut, and casual/transactional sex in females) but increasing other risk behaviours (e.g., male engagement in casual and commercial sex). We aimed to model the effect of socio-economic status, and associated economic strengthening interventions, in South Africa.

Methods and findings: We extended a previously-developed agent-based model of HIV, STIs, and fertility in South Africa to assess effects of education, employment, and per capita household income on sexual behaviours. We estimated these effects from literature and from calibration of the model to African randomized controlled trials of economic strengthening interventions. Population attributable fractions (PAFs) were calculated. We considered three intervention types, all targeting households with log per capita income below the national average: school support to reduce school dropout; vocational training for unemployed adults; and unconditional cash transfers. We estimate that low socio-economic status accounted for 13% of new HIV infections, 7% of incident STIs (gonorrhoea, chlamydia, and trichomoniasis) and 31% of teenage births in South Africa, over 2000-2020. However, because of uncertainties regarding effect sizes, confidence intervals around these PAFs are wide (1,50% for HIV; -1,19% for STIs; and 10,76% for teenage births). Over 2025-2040, none of the interventions are estimated to reduce HIV, STIs, or teenage births significantly, due to limited impact on secondary economic outcomes. The greatest impact would be that of school support on teenage births (a 5% reduction, 95% CI: -1,12%). Key limitations include the assumption of uniform STI treatment access across socio-economic strata, and the exclusion of possible socio-economic effects at a community level.

Conclusions: Although poverty is likely to be a significant driver of HIV, STIs, and teenage pregnancy in South Africa, precise quantification is challenging. Recently trialled economic strengthening interventions have insufficient impact on socio-economic status to reduce HIV and STIs significantly at a population level.

Background: The U.S. Food and Drug Administration (FDA) has the authority to require that sponsors conduct pediatric studies for certain new drugs under the Pediatric Research Equity Act (PREA). Here, we evaluate the characteristics and completion of these studies and assess the addition of pediatric-specific evidence generated from these studies into drug labeling.

Methods and findings: We performed a retrospective cohort study of all novel drugs approved by the FDA from 2011 to 2023 with at least one pediatric study requirement issued under PREA. Study status and outcomes were followed through 31 December 2024. We assessed completion of pediatric studies; addition of pediatric prescribing information to drug labels; and deviations from FDA-projected timelines. Of 552 novel drugs approved by the FDA between 2011 and 2023, 179 (32.4%) were subject to pediatric study requirements under PREA. Thirteen were later discontinued, resulting in a final cohort of 166 drugs and 338 pediatric study requirements. About half (51.8%) of the studies assessed efficacy. Among 222 studies with due dates by 31 December 2024, only 24.3% were completed by the original deadline. Over half (56.8%) received extensions of original timelines, by an average of 2.9 years (SD 2.0). At 10 years after drug approval, while 92.0% of studies were expected to have been completed, 59.5% had been completed. Of the 117 drugs with studies due by 31 December 2024, 54.7% (n = 64) had pediatric labeling updated with results from required studies. The mean time to addition of pediatric approval was 5.7 years (SD 2.6), whereas labeling additions reflecting lack of pediatric safety or benefit took an average of 8.3 years (SD 3.3) (p < 0.001). While 90.4% of drugs were expected to have all pediatric studies completed by 10 years, only 52.8% had any labeling changes reflecting data from the PREA-mandated studies. A limitation of this study is that publicly available FDA data provide limited detail on study design, execution, and reasons for delays, preventing assessment of study rigor and the factors contributing to delayed completion.

Conclusions: PREA was implemented to advance pediatric drug research and fill a critical gap in pediatric labeling of new drugs. However, our findings reveal frequent delays in study completion and labeling updates, with just over half of labeling additions completed 10 years after drug approval. Strengthening reporting requirements and expanding the FDA's enforcement authority are essential to ensuring that children receive timely access to safe and effective therapies supported by high-quality evidence.

Open research and data transparency are a bulwark against unethical activities, but can also introduce integrity risks. As with all public goods, freely available data can be exploited, and here we set out the case for the use of safeguarding practices.

Asymptomatic transmission, inequitable access to diagnostics, and rising antimicrobial resistance are major barriers to controlling the bacterial sexually transmitted infections (STIs) gonorrhea, chlamydia, and syphilis. Developing vaccines against these infections has therefore become a key STI research priority, requiring innovative research, expedited clinical development, and increased investment.

[This corrects the article DOI: 10.1371/journal.pmed.1004630.].