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Background The use of suboptimal controls in randomized trials of new cancer drugs can produce potentially unreliable clinical efficacy results over the current standard of care and expose patients to substandard therapy. We aim to investigate the proportion of randomized trials of investigational cancer drugs that used a suboptimal control arm and the number of trial participants at risk of exposure to suboptimal treatments in China. The association between the use of a suboptimal control and concluding statistical significance on the primary endpoint was also examined. Methods and findings This observational study included randomized controlled trials (RCTs) of cancer drugs that were authorized by specific Chinese institutional review boards between 2016 and 2021, supporting investigational new drug applications of these drugs in China. The proportion of trials that used a suboptimal control arm and the total number of trial participants at risk of exposure to suboptimal treatments were calculated. In a randomized trial for a specific condition, a comparator was deemed suboptimal if it was not recommended by clinical guidelines published in priori or if there existed a regimen with a higher level of recommendation for the indication. The final sample included 453 Phase II/III and Phase III randomized oncology trials. Overall, 60 trials (13.2%) adopted a suboptimal control arm. Among them, 58.3% (35/60) used comparators that were not recommended by a prior guideline for the indication. The cumulative number of trial participants at risk of exposure to suboptimal treatments totaled 18,610 by the end of 2021, contributing 15.1% to the total number of enrollees of all sampled RCTs in this study. After adjusting for the year of ethical approval, region of participant recruitment, line of therapy, and cancer site, second-line therapies (adjusted odds ratio [aOR] = 2.7, 95%CI [1.2, 5.9]), adjuvant therapies (aOR = 8.9, 95% CI [3.4, 23.1]), maintenance therapies (aOR = 5.2, 95% CI [1.6, 17.0]), and trials recruiting participants in China only (aOR = 4.1, 95% CI [2.1, 8.0]) were more likely to adopt a suboptimal control. For the 105 trials with publicly available results, no statistically significant difference was observed between the use of a suboptimal control and concluding positive on the primary endpoint (100.0% [12/12] versus 83.9% [78/93], p = 0.208). The main limitation of this study is its reliance on clinical guidelines that could vary across cancer types and time in assessing the quality of the control groups. Conclusions In this study, over one-eighth of randomized trials of cancer drugs registered to apply for regulatory approval in China used a suboptimal comparator. Our results highlight the necessity to refine the design of randomized trials to generate optimal clinical evidence for new cancer therapies., Author(s): Yichen Zhang 1, Dingyi Chen 1, Siyuan Cheng 2, Zhizhou Liang 1, Lu Yang 2, Qian Li 2, Lin Bai 1, Huangqianyu Li 3, Wei Liu 4, Luwen Shi [...]

Purpose: The purpose of this study is to evaluate the pattern, appropriateness, and cost of antidiabetic drugs prescribed for patients with Type 2 diabetes at primary healthcare facilities (PHFs) in China. Methods: We collected outpatient‐visit prescriptions from 363 PHFs in 31 cities covering eastern, central, and western regions of China. The visits of adult patients with Type 2 diabetes diagnosis were collected and classified the antidiabetic medication pattern of each patient use as recommended or non‐recommended according to Chinese guidelines. We then calculated the proportion of guideline‐recommended patterns and the average monthly cost for each pattern, overall and by region. Results: Of 33 519 prescriptions for Type 2 diabetes, most (73.9%) were for guideline‐recommended antidiabetic treatments. The proportion of guideline‐recommended prescriptions varied by region (eastern [75.9%], central [87.5%], and western [59.7%]). Metformin monotherapy was the most common guideline‐recommended treatment in all three regions (eastern [20.1%], central [28.0%], and western [24.6%]). The most common non‐guideline‐recommended treatments were monotherapy of insulin (eastern [16.5%], central [5.1%], and western [25.7%]) and traditional Chinese antidiabetic medicines (eastern [5.6%], central [5.7%], and western [11.1%]). The average monthly costs were lower for guideline‐recommended treatments compared to non‐recommended treatments in all regions (eastern [13.6 ± 15.4 USD vs. 28.1 ± 22.0 USD], central [9.8 ± 10.9 USD vs. 28.7 ± 19.4 USD], and western [17.9 ± 21.4 USD vs. 30.3 ± 23.6 USD]). Conclusions: The majority of patients with Type 2 diabetes received guideline‐recommended antidiabetic medications at PHFs in China, with only half of the prescriptions containing guideline‐recommended metformin. Utilization of guideline‐recommended therapies differed across regions. Tailored interventions to promote evidence‐based antidiabetic prescribing are urgently needed, especially in the undeveloped western region. [ABSTRACT FROM AUTHOR]

: Introduction: Engaging adolescents in HIV care and research promotes the development of interventions tailored to their unique needs. Guidelines generally require parental permission for adolescents to receive HIV care/testing or participate in research, with exceptions. Nevertheless, parental permission requirements can restrict adolescent involvement in care and research. To better appreciate prospects for policy reform, we sought to understand the perspectives of stakeholders involved in the development, review and implementation of policies related to adolescents living with HIV. Methods: Semi‐structured individual interviews (IDIs) were conducted from October 2019 to March 2020 with 18 stakeholders with expertise in the (1) development of policy through membership in the Law Society of Kenya or work as a health policy official; (2) review of policy through ethics review committee service; or (3) implementation of policy through involvement in adolescent education. IDIs were conducted in English by Kenyan social scientists, audio‐recorded and transcribed verbatim. We used thematic analysis to identify themes around how policies can be reformed to improve adolescent engagement in HIV care and research. Results: Our analysis identified three major themes. First, policies should be flexible rather than setting an age of consent. Stakeholders noted that adolescents’ capacity for engagement in HIV care and research depended on context, perceived risks and benefits, and “maturity”—and that age was a poor proxy for the ability to understand. Second, policies should evolve with changing societal views about adolescent autonomy. Participants recognized a generational shift in how adolescents learn and mature, suggesting the need for a more frequent review of HIV care and research guidelines. Third, adults should empower adolescent decision‐making. Stakeholders felt that caregivers can gradually involve adolescents in decision‐making to equip them to gain ownership over their health and lives, improving their confidence and capacity. Conclusions: Revising relevant laws to consider context, alternative measures of maturity, and evolving societal views about adolescence, along with supporting caregivers to assist in developing adolescent autonomy may promote more equitable and representative participation of adolescents in HIV care and research. Additional research should explore how to support caregivers and other adults to empower adolescents and improve stakeholder engagement in a more routine process of policy reform., INTRODUCTION Growing numbers of adolescents (ages 10–19) are living with HIV (ALHIV) [1]. There is an urgent need for representative participation of ALHIV in HIV testing, care and research on [...]

Objectives: To decelerate antibiotic resistance driven by inappropriate antibiotic prescribing, a prescription review and feedback (PRF) policy is implemented in primary healthcare institutions (PHIs) in Beijing, China. However, evaluation of PRF implementation in PHIs is scarce. This study aims to systematically identify the barriers and facilitators of PRF policy implementation to provide evidence for antimicrobial stewardship., Methods: We conducted key informant interviews with 40 stakeholders engaged in the implementation of PRF in Beijing, including physicians, pharmacists and administrators. Interviews were audio recorded and transcribed verbatim. We coded the interview transcripts and mapped informant views to domains of the Theoretical Domains Framework. We then used a behaviour change wheel to suggest possible behavioural interventions., Results: Procedural knowledge ( Knowledge ) and skills ( Skill ) of PRF were possessed by stakeholders. They felt responsible to promote the appropriate use of antibiotics ( Social/professional role and identity ) and believed that PRF could help to change inappropriate provider behaviours ( Behavioural regulation) in prescribing antibiotics ( Beliefs about consequences ) under increased intention on antibiotic use ( Stages of change ). Moreover, informants called for a more unified review standard to enhance PRF implementation ( Goals ). Frequently identified barriers to PRF included inadequate capacity ( Skill) , using punishment mechanism ( Behaviour regulation ), reaching consistently lower antibiotic prescription rates ( Goals ), lack of resources ( Environmental context and resources ) and perceived pressure coming from patients ( Social influences )., Conclusions: Stakeholders believed that PRF implementation promoted the rational use of antibiotics at PHIs in Beijing. Still, PRF was hampered by inconsistencies in review process and resources needed for PRF implementation., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)