随着近年来新的镰状细胞病(SCD)疗法的管道急剧增加,确保监管机构决策有足够证据的时机已经成熟,付款人,临床医生,和病人。通过有效的汇总分析和间接比较,协调介入试验中选择的结果可实现最佳的试验后评估和决策。我们雇佣了一个结构化的,多利益相关者共识过程,以开发用于SCD干预临床试验的核心结果集(COS)。
CoreSCD采用了改进的Delphi方法,该方法改编自有效性试验中的核心结果措施(COMET)计划建议的标准。通过有针对性的文献综述和由11名成员组成的咨询委员会的投入,制定了候选结果的初始列表。成立了一个由44名成员组成的多方利益相关者德尔福小组,其中包括患者和家庭成员,倡导者,临床医生,研究人员,付款人,卫生技术评估员,来自政府机构的代表,和行业代表。患者/倡导者占Delphi小组的25%,在达成共识之前提供了定向和培训,以确保所有人都准备有意义地参与。小组成员完成了三轮在线调查,以评估候选结果对纳入COS的重要性。在每轮投票之间提供了摘要数据,并在第二轮和第三轮投票之间举行了面对面的共识会议。在每一轮投票后都适用共识规则,以消除不符合预定保留标准的结果。
就两套核心成果达成了共识。用于疾病改善疗法试验的最终COS包括10个结果,用于急性干预试验的COS包括6个结果。这两个核心集包括临床结果以及与功能/生活质量相关的结果。资源利用率,和生存/死亡率。
在SCD的临床开发计划中使用COS将有助于确保相关的,一致的结果可用于整个产品生命周期的决策。
With the dramatic increase in the pipeline for new sickle cell disease (SCD) therapies in recent years, the time is ripe to ensure a robust body of evidence is available for decision making by regulators, payers, clinicians, and patients. Harmonization of the outcomes selected across interventional trials enables optimal post-trial appraisal and decision making through valid pooled analyses and indirect comparisons. We employed a structured, multi-stakeholder
consensus process to develop core outcome sets (COS) for use in clinical trials of SCD interventions.
CoreSCD utilized a modified Delphi method adapted from the standards recommended by the Core Outcome Measures in Effectiveness Trials (COMET) Initiative. An initial list of candidate outcomes was developed through a targeted literature review and input from an 11-member advisory committee. A 44-member multi-stakeholder Delphi Panel was established and included patients and family members, advocates, clinicians, researchers, payers, health technology assessors, representatives from government agencies, and industry representatives. Patients/advocates comprised 25% of the Delphi Panel and orientation and training was provided prior to the
consensus process to ensure all were prepared to participate meaningfully. Panelists completed three rounds of an online survey to rate the importance of candidate outcomes for inclusion in the COS. Summary data was provided between each voting round and an in-person
consensus meeting was held between the second and third round of voting.
Consensus rules were applied following each round of voting to eliminate outcomes that did not meet predetermined criteria for retention.
Consensus was reached for two core outcome sets. The final COS for trials of disease-modifying therapies includes ten outcomes and the COS for trials of acute interventions includes six outcomes. Both core sets include clinical outcomes as well as outcomes related to functioning/quality of life, resource utilization, and survival/mortality.
Use of the COS in clinical development programs for SCD will help to ensure that relevant, consistent outcomes are available for decision making across the product lifecycle.