Multicenter studies accrue more patients, but take longer to complete

We had a peppy discussion of an article, "Multi-institutional Phase I Trials of Anticancer Agents" by Dowlati et al, in our phase-1 oncology meeting on Thursday, so I thought I would share some of the discussion with you. Briefly, this article sought to investigate multi-institution phase-1 trials, as compared to single institution trials. They looked at all phase-1 cancer trials published in the Journal of Clinical Oncology and Clinical Cancer Research. This turned up 463 trials. They then went through and collected information about each trial, and compared single to multi-institution studies.

The advantage behind multi-institution studies (at least one advantage) is that you have a larger pool to pick from, and therefore the study will accrue faster. However, this study would appear to refute that assumption, as it revealed that multi-institution trials take longer and accrue more patients.

However, it seems there are many confounders. Notably, they did not account for the size of the institution in determining time of accrual. It would seem obvious that larger institutions (which do not necessarily need to open multi-institution studies) would be able to accrue faster than many smaller centers. This study also did not account for sites that were added on later — perhaps a single institution study became a multicenter study because of slow accrual. This would, I think, more accurately be bias, rather than confounding.

It is also possible that their use of only two journals presented a selection bias, as those two journals are really among the preeminent phase-1 journals that strive to present novel drugs and study designs, lending themselves to complicated studies, which may be the slowest to accrue.

Lastly, what I wish this study had addressed was the safety of conducting trials of early experimental chemotherapy and targeted therapy at multiple sites. Certainly we all have heard stories of patients at one site having toxicity, but the word not getting out quickly enough so that no other patients are treated. That, I think, represents the biggest challenge when multiple cancer centers are involved. I do not think multiple site trials will go away (nor do I think they should), but this is an intriguing article nonetheless.