Gaertner Jan, Weingärtner Vera, Lange Stefan, Hausner Elke, Gerhardus Ansgar, Simon Steffen T, Voltz Raymond, Becker Gerhild, Schmacke Norbert
Department of Palliative Care, University Medical Center Freiburg, Freiburg, Germany; Palliative Care Center of Excellence for Baden-Württemberg, Baden-Württemberg, Germany.
Department of Palliative Medicine, University Hospital of Cologne, Cologne, Germany.
PLoS One. 2015 Sep 1;10(9):e0136640. doi: 10.1371/journal.pone.0136640. eCollection 2015.
Randomized controlled trials (RCTs) are important sources of information on the benefits and harms patients may expect from treatment options. The aim of this structured literature review by the German Institute for Quality and Efficiency in Health Care was to explore whether and how the end-of-life (EoL) situation of patients with advanced cancer is considered in RCTs investigating anti-cancer treatments.
Our journal pool comprised 19 medical journals, namely five preselected key general medical journals as well as 14 specialist journals (mainly cancer) identified via a scoping search. We systematically searched these journals in MEDLINE to identify RCTs investigating anti-cancer treatments for the following four cancer types: glioblastoma, lung cancer (stage IIIb-IV), malignant melanoma (stage IV), and pancreatic cancer (search via OVID; November 2012). We selected a representative sample of 100 publications, that is, the 25 most recent publications for each cancer type. EoL was defined as a life expectancy of ≤ two years. We assessed the information provided on (1) the descriptions of the terminal stage of the disease, (2) the therapeutic goal (i.e. the intended therapeutic benefit of the intervention studied), (3) the study endpoints assessed, (4) the authors' concluding appraisal of the intervention's effects, and (5) the terminology referring to the patients' EoL situation.
Median survival was ≤ one year for each of the four cancer types. Descriptions of the terminal stage of the disease were ambiguous or lacking in 29/100 publications. One or more therapeutic goals were mentioned in 51/100 publications; these goals were patient-relevant in 38 publications (survival alone: 30/38; health-related quality of life (HRQoL) or HRQoL and survival: 6/38; symptom control or symptom control and survival: 2/38). Primary endpoints included survival (50%), surrogates (44%), and safety (3%). Patient-reported outcomes (PROs) were assessed in 36/100 RCTs. The implications of treatment-related harms for the patients were discussed in 22/100 appraisals. Terminology referring to the patients' EoL situation (e.g. "terminal") was scarce, whereas terms suggesting control of the disease (e.g. "cancer control") were common.
The EoL situation of patients with advanced cancer should be more carefully considered in clinical trials. Although the investigation and robust reporting of PROs is a prerequisite for informed decision-making in healthcare, they are rarely defined as endpoints and HRQoL is rarely mentioned as a therapeutic goal. Suggestions for improving standards for study design and reporting are presented.
随机对照试验（RCT）是有关患者可能从治疗方案中预期获得的益处和危害的重要信息来源。德国医疗质量与效率研究所进行的这项结构化文献综述的目的是探讨在调查抗癌治疗的随机对照试验中，是否以及如何考虑晚期癌症患者的临终（EoL）情况。
我们的期刊库包括19种医学期刊，即5种预先选定的主要综合医学期刊以及通过范围检索确定的14种专业期刊（主要是癌症方面的）。我们在MEDLINE中系统检索这些期刊，以识别针对以下四种癌症类型调查抗癌治疗的随机对照试验：胶质母细胞瘤、肺癌（IIIb-IV期）、恶性黑色素瘤（IV期）和胰腺癌（通过OVID检索；2012年11月）。我们从100篇出版物中选取了具有代表性的样本，即每种癌症类型的25篇最新出版物。EoL被定义为预期寿命≤两年。我们评估了所提供的关于以下方面的信息：（1）疾病终末期的描述；（2）治疗目标（即所研究干预措施预期的治疗益处）；（3）评估的研究终点；（4）作者对干预效果的总结性评价；（以及5）提及患者EoL情况的术语。
四种癌症类型中每种的中位生存期均≤一年。100篇出版物中有29篇对疾病终末期的描述含糊不清或缺乏相关内容。100篇出版物中有51篇提到了一个或多个治疗目标；其中38篇出版物中的这些目标与患者相关（仅生存：30/38；健康相关生活质量（HRQoL）或HRQoL与生存：6/38；症状控制或症状控制与生存：2/38）。主要终点包括生存（50%）、替代指标（44%）和安全性（3%）。100项随机对照试验中有36项评估了患者报告结局（PROs）。100项评价中有22项讨论了治疗相关危害对患者的影响。提及患者EoL情况的术语（如“终末期”）很少，而暗示疾病得到控制的术语（如“癌症控制”）很常见。
在临床试验中应更仔细地考虑晚期癌症患者的EoL情况。尽管对PROs进行调查和有力报告是医疗保健中做出明智决策的前提条件，但它们很少被定义为终点，并且HRQoL很少被提及为治疗目标。本文提出了改进研究设计和报告标准的建议。
