背景:通过模拟技术使药物致盲是控制研究者和受试者主观偏见的重要手段。然而,临床试验在安慰剂药物生产中面临重大挑战,许多试验不能双盲。
目的:本研究旨在确定临床试验中非盲和盲评估结果之间的一致性,并开拓控制信息偏倚的策略。特别是在双盲法不可行的试验中.
方法:在这项调查中,一项研究糖尿病足感染(DFIs)的随机对照试验(RCT)被用作代表性病例.在这次审判中,DFI的分级,根据美国传染病学会(IDSA)和国际糖尿病足工作组(IWGDF)的指导方针,用作主要疗效指标。从RCT中随机选择16名患者的样本,和DFI分级由非盲研究者和盲中心阅读研究者共同评估.然后部署一致性测试以比较评估结果,为我们提出的有效盲法评估策略奠定基础。此外,在本研究结束时收集了其他观点,包括参与设计和进行最近盲法评估试验的人员。
结果:5名受试者因照片质量或缺乏治疗后随访而被排除。比较11例受试者治疗后IDSA/IWGDF分级结果(实验组6例,对照组5例),一致性检验显示非盲法和中心阅读盲法评价结果不一致(Kappa=0.248,p=0.384).在实验组中,3例患者在非盲法评价中判定为1级,在中心阅读盲法评价中判定为2级;对照组,3例病例在非盲法评估中被判定为2级,在中心阅读盲法评估中被判定为1级.在22个治疗后的测定中,这两个病例的总和为27%(6/22)。此外,研究人员提出了几种在临床试验中实施盲化评估的策略,其中包括人员分配等方面,培训,参与者管理,试验药物管理,功效指标收集,和安全事件管理。
结论:该研究强调,来自非盲点研究者的评估可能会夸大实验组的功效,并且深层伤口可能对通过中心阅读照片进行观察提出挑战。这些发现强调了在开放临床试验中进行客观评估的必要性,尤其是那些以伤口观察为主要疗效指标的患者。该研究表明,在每个地点都采用独立的盲人调查员,辅以一套全面的标准操作程序进行盲法评估。这些措施可以有效地抵消主观偏见,从而提高了公开临床试验结果的可信度和一致性。这些发现和建议的含义可能对未来开放临床试验的设计和执行具有重要意义。有可能提高该领域临床研究的质量。
背景:ChiCTR2000041443。2020年12月注册。
BACKGROUND: Blinding drugs through simulation techniques is an important means to control the subjective bias of investigators and subjects. However, clinical trials face significant challenges in the placebo production of drugs, and many trials cannot be double-blinded.
OBJECTIVE: This study was conducted to ascertain the consistency between non-blind and blind evaluation results in clinical trials and to pioneer strategies to control information bias, particularly in trials where double-blinding is not feasible.
METHODS: In this investigation, a randomized controlled trial (RCT) studying diabetic foot infections (DFIs) was utilized as a representative case. In this trial, the grading of DFIs, as per guidelines by the Infectious Disease Society of America (IDSA) and International Working Group on Diabetic Foot (IWGDF), was used as the primary efficacy indicator. A sample of sixteen patients was randomly chosen from the RCT, and DFI grading was assessed jointly by both non-blinded investigators and blinded center-reading investigators. A consistency test was then deployed to compare the evaluation results, forming the basis for our proposed strategies for effective blinded evaluation. In addition, other perspectives were collected at the end of this study, including with those involved in designing and conducting the recent blinded evaluation trial.
RESULTS: Five subjects were excluded due to the quality of photos or the lack of post-treatment visits. The post-treatment IDSA/IWGDF grading results were compared in 11 subjects (experimental group=6, control group=5), and the consistency test showed inconsistent results between the non-blinded and center reading blinded evaluations (Kappa=0.248, p=0.384). In the experimental group, three cases were judged as grade 1 in the non-blinded evaluation and grade 2 in the central reading blinded evaluation; in the control group, three cases were judged as grade 2 in the non-blinded evaluation and grade 1 in the central reading blinded evaluation. The sum of these two cases in 22 post-treatment determinations was 27% (6/22). Furthermore, researchers propose several strategies for implementing blinded evaluations in clinical trials after this trial, which encompass aspects such as staff allocation, training, participant management, trial drug administration, efficacy indicator collection, and safety event management.
CONCLUSIONS: The study highlighted that evaluations from non-blinded site investigators may potentially exaggerate the efficacy of the experimental group and that deep wounds can present challenges for observation via center-reading photos. These findings underline the vital necessity for objective assessment in open clinical trials, especially those where wound observation serves as the primary efficacy indicator. The study suggests the adoption of independent blinded investigators at each site, complemented by a comprehensive set of standard operating procedures for blinding evaluation. These measures could serve as an effective counterbalance to subjective bias, thereby augmenting the credibility and consistency of results in open clinical trials. The implications of these findings and recommendations could be of great significance for the design and execution of future open clinical trials, potentially bolstering the quality of clinical research in this area.
BACKGROUND: ChiCTR2000041443. Registered on December 2020.