Takashi Kasal', Yuichiro Ohe1, Kazuto Nishio2, Hideo Kunltoh', Tomohide Tamura', Ikuo ..... Ando M, Eguchi K, Shinkai T, Tamura T, Ohe Y, Yamamoto N, et al.
Jpn J Clin OncoI1998;28(3 )214-221
Factors that Influence the Eligibility of Cases for Inclusion in Clinical Trials Takashi Kasal', Yuichiro Ohe 1, Kazuto Nishio2, Hideo Kunltoh', Tomohide Tamura', Ikuo Sekine1, Kaoru Kubota 1, Noboru Yamamoto 1, Yoichi Nakamura1, Tetsu ShinkaP, Tetsuro Kodama 1 and NagahiroSaij02 and the Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group 1Division of Medical Oncology, National Cancer Center Hospital and 2Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan
Key words: clinical trial - ineligibility - quality assurance - central registration system
INTRODUCTION For many years there were few therapeutic options for patients with lung cancer; surgery and radiotherapy were the only available treatments. About twenty years ago, chemotherapy to which disseminated lung cancer responded began to appear. Recently,
Received May 9, 1997; accepted October 1, 1997 For reprints and all correspondence: Nagahiro Saijo, Pharmacology Division, National Cancer Center Research Institute, I-I, Tsukiji 5-chome, Chuo-ku, Tokyo 104, Japan Abbreviations: LCCSG, the Lung Cancer Chemotherapy Study Group; JCOG, Japan Clinical Oncology Group; JCO, the Journal of Clinical Oncology; PS, performance status; ITT, intention-to-treat; PC, protocol-compatible
new treatment methods have been emerging. Many new chemotherapeutic agents have appeared, and various new techniques and methods have been developed for surgery and radiotherapy. It is necessary to determine the optimal choice or combination of these therapies. Most inoperable lung cancer patients have little hope of cure, and in these patients we therefore aim to achieve good palliation, including the prolongation of survival and the improvement of symptoms and of quality of life. The differences in palliative effects among these therapies are not marked. Therefore it is necessary for us to conduct high quality clinical trials. There are many sources and types of bias and error which influence the quality of clinical trials and which need to be minimized. One contributing error is the registration of ineligible cases. Ineligible cases are the cases that do not meet the eligibility criteria, or that fall under the exclusion criteria. In clinical trials,
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Background: It is important to minimize the incidence of ineligible cases to improve the quality of clinical trials. To determine factors which may influence the incidence of ineligible cases, the incidence of and reasons for ineligibility in clinical trials were retrospectively analyzed. Methods: We retrospectively examined the incidence of and reasons for ineligibility for inclusion in eight clinical trials conducted by the Lung Cancer Chemotherapy Study Group of the Japan Clinical Oncology Group and four trials financed by trust funds from a pharmaceutical company. Results: In these 12 clinical studies, the incidence of ineligibility was 4.20/0 (32/762) (range 0-10.6%). Specific factors that might influence the incidence of ineligible cases were then analyzed. There was a significant difference in the incidence of ineligibility between the methods of registration (P< 0.05). The incidences using a central registration and without using a central registration system were 2.80/0 (9/322) and 5.20/0 (23/440) respectively. We also analyzed ineligible cases in clinical studies published in the Journal of Clinical Oncology. In clinical studies published in the Journal of Clinical Oncology recently and 10 years ago, the incidences of ineligible cases were 5.0% (942/18 878) and 4.1 % (206/4995) respectively. In clinical studies on lung cancer published in the Journal of Clinical Oncology from 1984to 1995,the incidence of ineligible cases was 4.7% (900/19 116). There was no significant difference in the incidence of ineligible cases between our 12 studies and the Journal of Clinical Oncology clinical studies by the X2 test (P> 0.05). Conclusions: We conclude that the incidence of ineligible cases in our studies is similar to that in clinical trials published in the Journal of Clinical Oncology. Central registration systems are useful for checking for ineligibility, and to increase the quality of clinical trials.
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Jpn J Clin Oneol 1998;28(3) Table 1. Relationship between the incidence of ineligible cases and characteristics in clinical trials Characteristics
Trials
No. of cases Ineligible/total
(%)
No. of cases entered into study ~60
6
26/6
(4.1)
