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Journal of Clinical Oncology, Vol 23, No 6 (February 20), 2005: pp. 1334-1335 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.273
They Also Serve Who Only Stand and Wait: Do Individual Clinical Researchers, Too? Hoping for Individual Patient Data As Public DomainDivision of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan
Department of Medicine II, Okayama University Medical School, Okayama, Japan To the Editor: We have presented two meta-analyses regarding chemotherapy for non–small-cell lung cancer (NSCLC) based on the abstracted data (AD)1,2 and received an editorial comment about them from Dr Piedbois and Dr Buyse.3 We have no objection to their comments that state individual patient data (IPD)-based meta-analysis is more ideal than AD-based meta-analysis to draw inference, as they have cautioned for a long time.4 With all due respect to them, we have to say that we are still dissatisfied with their comments and would like to express our opinions. "Which treatment is better at present, adjuvant chemotherapy or surgery alone?" This is one of the simple questions that all clinicians involved in NSCLC treatment still encounter in their daily practices, and this question was the reason that motivated us to attempt the analysis.2 Although we had realized the result of an earlier meta-analysis published in 1995,5 we did not think that the issue had been concluded when we planned the analysis. Approximately half of the studies included in our analysis still had continued patient enrollment even after 1995, indicating the evidence by IPD-based analysis was not convincing enough to stop these trials. The clinical researchers involved should not have intended to conduct the demonstrational trials for proven efficacy of adjuvant chemotherapy for NSCLC; therefore, we are certain that our topic has some degree of positive significance, and provides justification for us to carry out an AD-based meta-analysis. We assume that the Journal of Clinical Oncology published our article with the same point of view, and the indication in the editorial, that our analysis is a retread of a proven issue, is beside the point. Editorialists also indicated that the analyses in each individual trial reported might be biased and were far from reliable to summarize by AD-based analysis. Frankly speaking, this indication is quite puzzling for us, considering it is from the editorialists at a medical journal. The medical articles in the journals are one of the most important sources for clinicians in their daily practices, and it is essential for us to see clear evidence for this indication so that we can fully take advantage of it. Another subject we have to be attentive to is how much of the precise conclusion would be drawn by IPD-based analysis compared with AD-based analysis to produce the main outcome of interest. Several articles are available relating to this issue that define AD-based analysis as less reliable6,7; however, the serious problem in the comparison is that the studies examined in each method are all different. Conclusions should be made based on the direct comparison between these two methods using exactly the same studies. For example, Hamada et al8 recently presented the IPD-based meta-analysis for adjuvant chemotherapy using tegafur plus uracil for NSCLC. They used six studies, and five of them were included in our analysis.2 When we analyzed with additional abstracted data of this nonoverlapped study,9 the summary hazard ratio for overall survival with tegafur plus uracil adjuvant chemotherapy is 0.76 (95% CI, 0.64 to 0.89; P = .001), whereas that in their intent-to-treat analysis is 0.76 (95% CI, 0.64 to 0.91; P = .0025). Although we still cannot rule out the potential bias in AD-based analysis, the main conclusions are the same in both analyses. Therefore, one may hypothesize that both methods would give similar estimates for the main outcome when exactly the same studies are examined, and this hypothesis must be evaluated in the future study from the scientific point of view. We have lately heard that another IPD-based analysis on adjuvant chemotherapy in NSLCS is underway, and we eagerly await the results to examine this issue. Considering the huge resource burden for IPD-based analysis (as mentioned in the editorials), we must say it is extreme to conclude that AD-based analysis is unreliable and to limit its role to simple hypothesis generation at present. Lastly, as the editorialists mentioned, how an outlier study is dealt with is important in meta-analysis. Coldtiz et al10 pointed out the potential danger of study exclusion by source of heterogeneity. If study exclusion aims to make studies homogeneous under the pretext of removing random errors, it may lead to a serious bias. We do not believe that homogeneity of the results across the studies is a prerequisite for meta-analysis; however, if that kind of homogeneity exists, there should be no reason to conduct meta-analysis except to obtain a statistically significant result. This is a common issue for both IPD- and AD-based meta-analyses, and should be considered seriously. We believe, despite several limitations, that AD-based meta-analysis still has a substantial role in the medical science until an ideal situation for gold standard analysis is established. Having faith in the strength of IPD-based meta-analysis, we sincerely hope that all the primary investigators in the clinical trial groups seriously consider establishing the ideal situation for smooth research as public domain, which enables independent clinical researchers to examine IPD with their new hypothesis, instead of limiting its use to the authorities. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Hotta K, Matsuo K, Ueoka H, et al: Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22:3852-3859, 2004
2. Hotta K, Matsuo K, Ueoka H, et al: Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer: Reappraisal with a meta-analysis of randomized controlled trials. J Clin Oncol 22:3860-3867, 2004
3. Piedbois P, Buyse M: Meta-analysis based on abstracted data: A step in the right direction, but only a first step. J Clin Oncol 22:3839-3841, 2004 4. Piedbois P, Buyse M: Meta-analyses need time, collaboration, and funding. J Clin Oncol 12:878-880, 1994[Medline]
5. Chemotherapy in non-small cell lung cancer: A meta-analysis using updated data on individual patients from 52 randomised clinical trials: Non-small Cell Lung Cancer Collaborative Group. BMJ 311:899-909, 1995 6. Stewart LA, Parmar MK: Meta-analysis of the literature or of individual patient data: Is there a difference? Lancet 341:418-422, 1993[CrossRef][Medline] 7. Duchateau L, Pignon JP, Bijnens L, et al: Individual patient-versus literature-based meta-analysis of survival data: Time to event and event rate at a particular time can make a difference, an example based on head and neck cancer. Control Clin Trials 22:538-547, 2001[CrossRef][Medline] 8. Hamada C, Ohta M, Wada H, et al: Survival benefit of oral UFT for adjuvant chemotherapy after completely resected non-small-cell lung cancer. Proc Am Soc Clin Oncol 22:617, 2004 (abstr 7002)
9. Wada H, Hitomi S, Teramatsu T: Adjuvant chemotherapy after complete resection in non-small-cell lung cancer: West Japan Study Group for Lung Cancer Surgery. J Clin Oncol 14:1048-1054, 1996
10. Colditz GA, Burdick E, Mosteller F: Heterogeneity in meta-analysis of data from epidemiologic studies: A commentary. Am J Epidemiol 142:371-382, 1995 Related Articles
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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