We evaluated the number and characteristics of randomized controlled trials (RCTs) addressing hematopoietic stem cell transplantation (HSCT) for patients with hematological malignancies, comparing the productivity of US and Europe. A MEDLINE search was conducted to identify all published RCTs for the management of adult patients with hematological malignancies from January 1992 to December 2003. Eighty-three of the 306 trials identified included HSCT as one of the treatment arms. The US produced 25, Europe 54, and all other countries four. Four European countries, France, Italy, Germany, and UK (FIGU), produced 32 out of the 54 European studies. Significant differences emerged when focus of the study and accrual numbers were analyzed. Trials comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% of US studies (P ¼ 0.001). US trials accrued a mean of 110.2 patients per study, as compared to 222.6 in FIGU studies (P ¼ 0.006) and 205.3 when all non-US countries are considered (P ¼ 0.01). Our conclusions are that US transplant RCT have focused on issues other than the comparison of HSCT to standard therapies. There is serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.

Introduction: Evidence-based medicine defines standard therapies primarily from Phase III randomized controlled trials (RCT), when available. In this report we examined trends in ther number and characteristics of phase III RCT addressing the management of adult patients with hematological malignancies, comparing the patterns of activity in the US and Europe. Materials and Methods: We attempted to identify all phase III RCT published in the English medical literature from 1/1992 to 12/2003. A systematic search of Medline and published references was conducted using multiple keywords for each malignancy as well as for hematopoeitic stem cell transplant (HSCT). We cross-referenced the data by searching individual journals, as well as the ASH education books from 1998–2003. Studies published in abstract form only were not included. Results: We identified 306 published RCT that accrued a total of 4899 patients. Eighty-three of these studies included HSCT with a total accrual of 2081 patients. Country of origin included: US (n= 25), Europe (n=54), other (n=4). Four European countries (France, Italy, Germany and UK: FIGU) with a combined population similar to that of the US produced 32 studies. This figure for FIGU does not include their contributions to 12 separate European cooperative trials. There were no significant trends in the number of trials published per year during the study period. However, significant differences emerged when the focus of the studies and the accrual numbers were analyzed. RCTs comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% (1 out of 25) of US studies (p <.001). US trials accrued a mean of 110.2 patients per study, as compared to 205.3 in other countries and 222.6 in FIGU studies (p= .006). In multivariate analysis, only focus of study was independently related to greater study size (p<.001). Among the remaining 223 trials not involving HSCT (US produced 68 and FIGU 77), a significant trend for increasing numbers of trials published per year during the study period was documented (p=.015). No significant differences in the mean number of patients accrued per trial (US= 279.5, other countries= 302.8 and FIGU= 347.8), or in the focus of the studies were observed in univariate or multivariate analysis. Conclusions: While there has been an increase in the number of Phase III RTCs in patients with hematological malignancies published during 1992–2003, the activity for HSCT trials has remained stationary. US HSCT trials have focused on issues other than the comparison of HSCT to standard therapies, such as graft manipulation, growth factors and graft versus host disease. US HSCT have accrued significantly fewer patients per study. The reasons for these differences are not apparent from our data, and may include patient and/or physician attitudes/biases toward phase III trials, issues of financial coverage for the HSCT procedure and/or health care delivery policies. There is a serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.