Updating Reports of Phase 3 Clinical Trials for Cancer
Corresponding Author: Ian F.Tannock, MD, PhD, Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, 610 University Ave, Toronto, ON M5G2M9, Canada (ian.tannock@uhn.ca).
Elimova E, Moignard S, Li X, et al. Updating Reports of Phase 3 Clinical Trials for Cancer. JAMA Oncol 2021.
Phase 3 randomized clinical trials (RCTs) are usually reported after a predetermined number of events (death or disease progression) have occurred, when survival curves remain poorly defined. Updated reports are important in providing mature data.
3期隨機臨床試驗（RCT）通常發生於預定數目的事件（死亡或疾病進展）後，且當生存曲線仍然不明確時。更新的報告對於提供成熟的數據很重要。
To evaluate the proportion of phase 3 RCTs for cancer that are updated and the factors that are associated with updating them and, for updated trials, to compare initial and updated results.
用於評估更新的癌症3期RCT的比例以及與相關的因素，並且對於更新的試驗，比較初始結果和更新結果。
DESIGN, SETTING, AND PARTICIPANTS 設計，設定及參與者This study identified reports of 2-group RCTs with a sample size of at least 100, published in 6 major journals between 1990 and 2010, that evaluated drug treatments for breast, lung, or prostate cancer. PubMed and abstracts of large cancer conferences were searched to identify updated (or earlier) reports of the same trials published up to 2019. Logistic regression was used to identify factors associated with the provision of updated reports. The hazard ratios defining the relative treatment effects for the primary and secondary end points between the initial and updated reports were compared.
這項研究確定了1990至2010年間在6個主要期刊上發表的樣本量至少為100的兩組隨機對照試驗(RCT)的報告，這些報告評估了乳腺癌、肺癌或前列腺癌的藥物治療。搜索PubMed和大型癌症會議的摘要，以確定截至2019年發表的相同試驗的最新(或更早)報告。Logistic回歸用於確定與提供最新報告相關的因素。對初始報告和更新報告之間確定主要和次要終點的相對治療效果的危險比進行了比較。
MAIN OUTCOMES AND MEASURES 主要結果及措施Proportion of RCTs whose results are updated, factors associated with updating, and change in hazard ratio for the primary end point between initial and updated reports.
更新的隨機對照試驗的比例，與更新相關的因素，以及初始報告和更新報告之間主要終點的危險比的變化。
A total of 207 RCTs met the inclusion criteria, and 41 (20%) were found to have updated reports. The factors significantly associated with an update included positive trial results (odds ratio [OR], 8.7 [95% CI, 3.3-23.3]), larger trial size (OR, 1.0006 [95% CI,1.0000-1.0012]), evaluation of hormonal agents (OR, 5.8 [95% CI, 1.6-21.8]) or targeted agents (OR, 4.3 [95% CI, 1.3-14.6]) compared with chemotherapy, and evaluation of adjuvant therapy rather than therapy for advanced disease (OR, 8.0 [95% CI, 2.9-21.9]). For 31 trials for which initial and updated hazard ratios for the primary end point were available, the median hazard ratio increased from 0.66 (95% CI, 0.22-1.20) to 0.74 (95% CI, 0.32-1.19) (P < .001),indicating a decreased level of effectiveness.
共有207個隨機對照試驗符合納入標準，41個(20%)被發現更新了報告。與更新顯著相關的因素包括陽性試驗結果(優勢比[OR]，8.7[95%CI，3.3-23.3])，更大的試驗規模(OR，1.0006[95%CI，1.0000-1.0012])，與化療相比，對激素製劑(OR，5.8[95%CI，1.6-21.8])或靶向藥物(OR，4.3[95%CI，1.3-14.6])的評估，以及對輔助治療的評估，而不是對晚期疾病的治療(OR，8.0[95%CI，2.9-21.9])。對於31個主要終點的初始和更新風險比可用的試驗，中位風險比從0.66(95%可信區間，0.22-1.20)增加到0.74(95%可信區間，0.32-1.19)(P<0.001)，表明有效性水平降低。
CONCLUSIONS AND RELEVANCE 結論及意義Only 20% of reports of phase 3 clinical trials for breast, lung, and prostate cancer were updated. Original reports of such trials are based on relatively few events, and their results are immature; more mature data indicate a decreased level of effect in updated trials. Updated reporting to provide mature, long-term results of clinical trials should be mandated.
在乳腺癌、肺癌和前列腺癌的3期臨床試驗中，只有20%的報告得到了更新。這類試驗的原始報告基於相對較少的事件，其結果還不成熟；更成熟的數據表明，更新後的試驗的效果水平有所下降。應該強制要求更新報告，以提供成熟的、長期的臨床試驗結果。
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