Wednesday, February 27, 2013

It's Not Them, It's You

Are competing trials slowing yours down? Probably not.

If they don't like your trial, EVERYTHING ELSE IN
THE WORLD is competition for their attention.
Rahlyn Gossen has a provocative new blog post up on her website entitled "The Patient Recruitment Secret". In it, she makes a strong case for considering site commitment to a trial – in the form of their investment of time, effort, and interest – to be the single largest driver of patient enrollment.

The reasoning behind this idea is clear and quite persuasive:
Every clinical trial that is not yours is a competing clinical trial. 
Clinical research sites have finite resources. And with research sites being asked to take on more and more duties, those resources are only getting more strained. Here’s what this reality means for patient enrollment. 
If research site staff are working on other clinical trials, they are not working on your clinical trial. Nor are they working on patient recruitment for your clinical trial. To excel at patient enrollment, you need to maximize the time and energy that sites spend recruiting patients for your clinical trial.
Much of this fits together very nicely with a point I raised in a post a few months ago, showing that improvements in site enrollment performance may often be made at the expense of other trials.

However, I would add a qualifier to these discussions: the number of active "competing" trials at a site is not a reliable predictor of enrollment performance. In other words, selecting sites who are not working on a lot of other trials will in no way improve enrollment in your trial.

This is an important point because, as Gossen points out, asking the number of other studies is a standard habit of sponsors and CROs on site feasibility questionnaires. In fact, many sponsors can get very hung up on competing trials – to the point of excluding potentially good sites that they feel are working on too many other things.

This came to a head recently when we were brought in to consult on a study experiencing significant enrollment difficulty. The sponsor was very concerned about competing trials at the sites – there was a belief that such competition was a big contributor to sluggish enrollment.

As part of our analysis, we collected updated information on competitive trials. Given the staggered nature of the trial's startup, we then calculated time-adjusted Net Patient Contributions for each site (for more information on that, see my write-up here).

We then cross-referenced competing trials to enrollment performance. The results were very surprising: the quantity of other trials had no effect on how the sites were doing.  Here's the data:

Each site's enrollment performance as it relates to number of other trials it's running.
Competitive trials do not appear to substantially impact rates of enrollment.
 Each site is a point. Good sites (higher up) and poor enrollers (lower) are virtually identical in terms of how many concurrent trials they were running.

Since running into this result, I've looked at the relationship between the number of competing trials in CRO feasibility questionnaires and final site enrollment for many of the trials we've worked on. In each case, the "competing" trials did not serve as even a weak predictor of eventual site performance.

I agree with Gossen's fundamental point that a site's interest and enthusiasm for your trial will help increase enrollment at that site. However, we need to do a better job of thinking about the best ways of measuring that interest to understand the magnitude of the effect that it truly has. And, even more importantly, we have to avoid reliance on substandard proxy measurements such as "number of competing trials", because those will steer us wrong in site selection. In fact, almost everything we tend to collect on feasibility questionnaires appears to be non-predictive and potentially misleading; but that's a post for another day.

[Image credit: research distractions courtesy of Flikr user ronocdh.]

2 comments:

J Franceschi said...

Good points on your blog. At our center we conduct a lot of psychiatric research and as a site we are much more productive when we have various studies for mental health disorders. I like to refer to it as "Research Buffet" when we have at least one trial for ADHD, depression, anxiety, and bipolar disorder. There are many symptoms that overlap multiple disorders i.e. difficulty concentrating so when someone responds to an advertisement they will probably qualify for one of our studies. The multiple studies also allow us to pool our recruitment efforts to reach a wider audience rather than having a meager budget from one trial.

It is extremely devastating to small sites when you have a difficult to recruit trial and you pour a lot of resources into it and you don't get much out of it. It is much better to generate revenue through other trials and wait for candidates to trickle in for the difficult study. Otherwise, if we are investing all our resources into "their" one trial like some sponsors want then we may have to cut staff because we simply are not generating enough revenue. There is safety in diversifying and sponsors and CRO's benefit from that as well!

Paul Ivsin said...

Thanks for your comment, J -- I take it you're one of the sites on the upper right of the graph: successful with lots of trials. And your point is well taken that for some sites, having more trials actually improves performance.

I have also worked with a lot of small sites that succeed by staying focused on only a few trials, and being very selective about which ones they join. Sponsors in general need to be a bit more understanding that sites succeed for different reasons.