全国范围内强化实施胰腺癌护理最佳实践的影响（PACAP-1）：一项多中心阶梯式楔形整群随机对照试验

Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial.

作者信息

Mackay T M, Smits F J, Latenstein A E J, Bogte A, Bonsing B A, Bos H, Bosscha K, Brosens L A A, Hol L, Busch O R C, Creemers G J, Curvers W L, den Dulk M, van Dieren S, van Driel L M J W, Festen S, van Geenen E J M, van der Geest L G, de Groot D J A, de Groot J W B, Haj Mohammad N, Haberkorn B C M, Haver J T, van der Harst E, Hemmink G J M, de Hingh I H, Hoge C, Homs M Y V, van Huijgevoort N C, Jacobs M A J M, Kerver E D, Liem M S L, Los M, Lubbinge H, Luelmo S A C, de Meijer V E, Mekenkamp L, Molenaar I Q, van Oijen M G H, Patijn G A, Quispel R, van Rijssen L B, Römkens T E H, van Santvoort H C, Schreinemakers J M J, Schut H, Seerden T, Stommel M W J, Ten Tije A J, Venneman N G, Verdonk R C, Verheij J, van Vilsteren F G I, de Vos-Geelen J, Vulink A, Wientjes C, Wit F, Wessels F J, Zonderhuis B, van Werkhoven C H, van Hooft J E, van Eijck C H J, Wilmink J W, van Laarhoven H W M, Besselink M G

机构信息

Department of surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, the Netherlands.

Department of surgery, University Medical Center Utrecht, Utrecht, the Netherlands.

出版信息

Trials. 2020 Apr 16;21(1):334. doi: 10.1186/s13063-020-4180-z.

BACKGROUND

Pancreatic cancer has a very poor prognosis. Best practices for the use of chemotherapy, enzyme replacement therapy, and biliary drainage have been identified but their implementation in daily clinical practice is often suboptimal. We hypothesized that a nationwide program to enhance implementation of these best practices in pancreatic cancer care would improve survival and quality of life.

METHODS/DESIGN: PACAP-1 is a nationwide multicenter stepped-wedge cluster randomized controlled superiority trial. In a per-center stepwise and randomized manner, best practices in pancreatic cancer care regarding the use of (neo)adjuvant and palliative chemotherapy, pancreatic enzyme replacement therapy, and metal biliary stents are implemented in all 17 Dutch pancreatic centers and their regional referral networks during a 6-week initiation period. Per pancreatic center, one multidisciplinary team functions as reference for the other centers in the network. Key best practices were identified from the literature, 3 years of data from existing nationwide registries within the Dutch Pancreatic Cancer Project (PACAP), and national expert meetings. The best practices follow the Dutch guideline on pancreatic cancer and the current state of the literature, and can be executed within daily clinical practice. The implementation process includes monitoring, return visits, and provider feedback in combination with education and reminders. Patient outcomes and compliance are monitored within the PACAP registries. Primary outcome is 1-year overall survival (for all disease stages). Secondary outcomes include quality of life, 3- and 5-year overall survival, and guideline compliance. An improvement of 10% in 1-year overall survival is considered clinically relevant. A 25-month study duration was chosen, which provides 80% statistical power for a mortality reduction of 10.0% in the 17 pancreatic cancer centers, with a required sample size of 2142 patients, corresponding to a 6.6% mortality reduction and 4769 patients nationwide.

DISCUSSION

The PACAP-1 trial is designed to evaluate whether a nationwide program for enhanced implementation of best practices in pancreatic cancer care can improve 1-year overall survival and quality of life.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT03513705. Trial opened for accrual on 22th May 2018.

背景

胰腺癌的预后非常差。化疗、酶替代疗法和胆道引流的最佳实践已得到确定，但在日常临床实践中的实施情况往往不尽人意。我们假设，一项旨在加强这些胰腺癌护理最佳实践实施的全国性计划将改善患者的生存率和生活质量。

方法/设计：PACAP-1是一项全国性多中心阶梯式楔形整群随机对照优势试验。在为期6周的启动期内，荷兰的17个胰腺癌中心及其区域转诊网络以每个中心逐步随机的方式，实施胰腺癌护理中关于（新）辅助化疗和姑息化疗、胰酶替代疗法以及金属胆道支架使用的最佳实践。每个胰腺癌中心，一个多学科团队作为网络中其他中心的参照。关键的最佳实践是从文献、荷兰胰腺癌项目（PACAP）中现有全国性登记处的3年数据以及全国专家会议中确定的。这些最佳实践遵循荷兰胰腺癌指南和当前文献状况，并且可以在日常临床实践中执行。实施过程包括监测、回访、提供者反馈以及教育和提醒。患者结局和依从性在PACAP登记处进行监测。主要结局是1年总生存率（适用于所有疾病阶段）。次要结局包括生活质量、3年和5年总生存率以及指南依从性。1年总生存率提高10%被认为具有临床意义。选择了25个月的研究时长，这为17个胰腺癌中心死亡率降低10.0%提供了80%的统计效力，所需样本量为2142例患者，相当于全国死亡率降低6.6%以及4769例患者。