Centre for Health Economics and Medicines Evaluation, Bangor University, Ardudwy, Normal Site, Holyhead Road, Bangor, Gwynedd, Wales, LL57 2PZ, UK.
Pharmacoeconomics. 2024 Dec;42(12):1373-1394. doi: 10.1007/s40273-024-01418-3. Epub 2024 Sep 9.
BACKGROUND: The National Institute for Health and Care Excellence (NICE) may approve health technologies on condition of more evidence generated only in research (OiR) or only with research (OwR). NICE specifies the information needed to comply with its request, although it may not necessarily guarantee good quality and timely evidence for re-appraisal, before reaching a final decision. AIM: This study aimed to critically appraise the methods, quality and risk of bias of evidence generated in response to NICE OiR and OwR technology appraisal (TA) and highly specialised technologies (HSTs) recommendations. METHODS: NICE TAs (between March 2000 and September 2020) and HST evaluations (to October 2023) of medicines were reviewed. Conditional recommendations were analysed to identify the evidence requested by NICE for re-appraisal. The new evidence was analysed for compliance with NICE's request and assessed using the Cochrane Collaboration's tools for risk of bias in randomised trials and the ROBINS-I tool for non-randomised evidence. RESULTS: NICE made 54 conditional recommendations from TAs (13 OiR and 41 OwR) and five conditional recommendations for HSTs (all OwR). Of these, 16 TAs presented additional evidence for re-appraisal (9 OiR [69%] and 7 OwR [17%]) and three HSTs (3 OwR [60%]). Two of the nine re-appraised TAs with OiR recommendation and four of the seven OwR complied fully with NICE's request for further evidence, while all three from the HSTs complied. The majority of re-appraised TAs and HSTs included evidence that was deemed to be at serious, high, moderate or unclear risk of bias. Among the 26 randomised controlled trials from TAs assessed, eight were categorised as having low risk of bias in all domains and ten had at least one domain as a high risk of bias. Reporting was unclear for the remainder. Twenty-two non-randomised studies, primarily single-arm studies, were susceptible to biases mostly due to the selection of participants and to confounding. Two HSTs provided evidence from randomised controlled trials which were classified as unclear or high risk of bias. All non-randomised evidence from HSTs were categorised as moderate or serious risk of bias. CONCLUSIONS: There is widespread non-compliance with agreed data requests and important variation in the quality of evidence submitted in response to NICE conditional approval recommendations. Quality standards ought to be stipulated in respect to evidence contributing to re-appraisals following NICE conditional approval recommendations.
背景:国家卫生与保健卓越研究所(NICE)可能会根据在研究中生成的更多证据(OiR)或仅使用研究(OwR)的条件批准医疗技术。NICE 指定了遵守其要求所需的信息,尽管在做出最终决定之前,它不一定能保证重新评估的高质量和及时证据。
目的:本研究旨在批判性地评价针对 NICE OiR 和 OwR 技术评估(TA)和高度专业化技术(HST)建议生成的证据的方法、质量和偏倚风险。
方法:审查了 NICE 于 2000 年 3 月至 2020 年 9 月期间的 TA 和 2023 年 10 月之前的 HST 评估。分析了有条件的建议,以确定 NICE 重新评估所需的证据。分析了新证据是否符合 NICE 的要求,并使用 Cochrane 协作组的随机试验偏倚风险工具和 ROBINS-I 工具对非随机证据进行评估。
结果:NICE 做出了 54 项针对 TA(13 项 OiR 和 41 项 OwR)和 5 项针对 HST 的有条件建议(均为 OwR)。其中,16 项 TA 提供了额外的重新评估证据(9 项 OiR [69%]和 7 项 OwR [17%]),3 项 HST 提供了 3 项全部 OwR [60%]。9 项有条件的重新评估 TA 中有 2 项 OiR 推荐和 7 项 OwR 中有 4 项完全符合 NICE 对进一步证据的要求,而所有 3 项 HST 均符合。大多数重新评估的 TA 和 HST 都包含被认为存在严重、高、中或不明确偏倚风险的证据。在评估的 TA 中,26 项随机对照试验中,有 8 项在所有领域均被归类为低偏倚风险,有 10 项至少有一个领域为高偏倚风险。其余的报告不清楚。22 项非随机研究,主要是单臂研究,易受偏倚影响,主要是由于参与者的选择和混杂因素。2 项 HST 提供了来自随机对照试验的证据,这些证据被归类为不明确或高偏倚风险。所有来自 HST 的非随机证据均被归类为中或严重偏倚风险。
结论:在针对 NICE 有条件批准建议提交的证据方面,普遍存在不符合既定数据请求的情况,而且证据质量存在重要差异。在遵守 NICE 有条件批准建议后,应该规定证据质量标准。
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