癌症研究和药物研发可获得更理想的疗法,但是根据一项由Sloan-Kettering癌症中心的研究人员发表的报告指出,这些测试癌症药物的临床试验存在着很大的缺陷。
这项发表于2月1 日Clinical Cancer Research的研究报告,解释了为什么许多实验性药物无通过最后的大型且昂贵的临床测试。
研究人员发现,在他们审查的2003 年6月至2005 年6月间,共70项第II阶段研究中,只有9项研究清楚地定义用于评估对患者益处之标准。这些研究通常包含30到50 名患者,目标是评估是否应继续进行第III阶段的大型临床试验,这是决定该药物是否能用于癌症患者之最后测试。
研究人员指出,这是临床试验测试中不断衍生出的问题,因为即使当药物改变了,研究人员仍然使用一样的老方法来测量这些药物的效果。因此研究人员建议,当制药公司或实验室针对新的物质进行临床试验时,必须设定新的评估标准,才能更有效地评估药效及药物的安全性。
(资料来源 : Bio.com)
英文原文摘要:
Setting the Bar in Phase II Trials: The Use of Historical Data for Determining "Go/No Go" Decision for Definitive Phase III Testing
Andrew J. Vickers1,2, Vennus Ballen1 and Howard I. Scher1
Authors' Affiliations: Departments of 1 Medicine and 2 Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY
Requests for reprints: Andrew J. Vickers, Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10021. Phone: 212-639-4910; Fax: 212-639-4953; E-mail: vickersa@mskcc.org .
Purpose: Phase II trials aim to determine whether a cancer treatment is sufficiently promising to justify phase III study. Whether an agent is declared promising in a phase II trial depends on prespecified "null" and "alternative" rates of an outcome of interest such as tumor response. In some cases, the null must be determined with reference to historical data. We sought to determine the proportion of phase II trials that require historical data to establish the null and to determine how these historical estimates were derived.
Experimental Design: We conducted a systematic review of phase II trials published in the Journal of Clinical Oncology or Cancer in the 3 years to June 2005. Data were extracted following a prespecified protocol.
Results: We retrieved 251 papers, of which 117 were found to be ineligible; 70 of 134 included trials (52%) were defined as requiring historical data for design. Nearly half (32, 46%) of these papers did not cite the source of the historical data used, and just 9 (13%) clearly gave a single historical estimate as the rationale for the null. Trials that failed to cite prior data appropriately were significantly more likely to declare an agent to be active (82% versus 33%; P = 0.005). No study incorporated statistical methods to account for either sampling error or possible differences in case mix between the phase II sample and the historical cohort.
Conclusions: Many phase II trials require historical data to determine null response rates. Simple guidelines may improve design and reporting of such trials.
原文出处:Clinical Cancer Research 13, 972-976, February 1, 2007. Published Online First February 2, 2007;
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