Sorg Carolin, Schmidt Jan, Büchler Markus W, Edler Lutz, Märten Angela
Department of Surgery, University of Heidelberg, Heidelberg, Germany.
Pancreas. 2009 Jul;38(5):542-50. doi: 10.1097/MPA.0b013e31819d7370.
Clinical trials are a prerequisite for evidence-based medicine. Trial representativity by internal and external validities is an assumption for a transfer into the real world.
A questionnaire addressing several forms of bias was established. Randomized controlled trials for adjuvant treatment of pancreatic adenocarcinoma with an evidence level of lower than 2 were selected and evaluated for internal and external validities focusing on selection bias.
Four selected trials (European Study Group for Pancreatic Cancer 1 [ESPAC-1], Charité Onkologie Clinical Studies in GI Cancer 001 [CONKO 001], Radiation Therapy Oncology Group 97-04 [RTOG 97-04], and Adjuvant Chemoradioimmunotherapy of Pancreatic Carcinoma [CapRI]) proved to be evaluable. External validity was to a large extent given in the trials, whereby Radiation Therapy Oncology Group 97-04 included significantly more patients with better prognostic markers (negative for lymph nodes and T1/T2 tumors). Their inclusion and exclusion criteria are limited to the (unavoidable) restrictions for safety reasons and clinical restrictions. Comparison of participants with nonparticipants and with the target population via literature research proved to be preventive against selection and recruitment biases. A possible detection bias in the Charité Onkologie Clinical Studies in GI Cancer 001 trial cannot, however, be excluded.
The analyzed trials have acceptable internal and external validities despite some minor criticisms. The protocols could be transferred into the clinical routine. It is recommended to open the inclusion criteria of trials wider and to implement the comparison with the target population.
临床试验是循证医学的前提条件。通过内部和外部效度实现试验代表性是将试验结果应用于现实世界的一个假设。
设计了一份针对多种偏倚形式的问卷。选取证据水平低于2级的胰腺癌辅助治疗随机对照试验，重点从选择偏倚方面评估其内部和外部效度。
四项入选试验（欧洲胰腺癌研究组1 [ESPAC-1]、柏林夏里特医院胃肠癌临床研究001 [CONKO 001]、放射治疗肿瘤学组97-04 [RTOG 97-04]以及胰腺癌辅助放化疗免疫治疗[CapRI]）经证实可进行评估。试验在很大程度上具备外部效度，其中放射治疗肿瘤学组97-04纳入了更多具有较好预后标志物（淋巴结阴性及T1/T2期肿瘤）的患者。其纳入和排除标准仅限于出于安全原因的（不可避免的）限制以及临床限制。通过文献研究比较参与者与非参与者以及与目标人群，可预防选择和招募偏倚。然而，柏林夏里特医院胃肠癌临床研究001试验中存在检测偏倚的可能性无法排除。
尽管存在一些小的问题，但所分析的试验具有可接受的内部和外部效度。试验方案可应用于临床常规。建议放宽试验的纳入标准，并与目标人群进行比较。
