Wednesday, June 20, 2012

Faster Trials are Better Trials

[Note: this post is an excerpt from a longer presentation I made at the DIA Clinical Data Quality Summit, April 24, 2012, entitled Delight the Sites: The Effect of Site/Sponsor Relationships on Site Performance.]

When considering clinical data collected from sites, what is the relationship between these two factors?
  • Quantity: the number of patients enrolled by the site
  • Quality: the rate of data issues per enrolled patient
When I pose this question to study managers and CRAs, I usually hear that they believe there is an inverse relationship at work. Specifically, most will tell me that high-enrolling sites run a great risk of getting "sloppy" with their data, and that they will sometimes need to caution sites to slow down in order to better focus on accurate data collection and reporting.

Obviously, this has serious implications for those of us in the business of accelerating clinical trials. If getting studies done faster comes at the expense of clinical data quality, then the value of the entire enterprise is called into question. As regulatory authorities take an increasingly skeptical attitude towards missing, inconsistent, and inaccurate data, we must strive to make data collection better, and absolutely cannot afford to risk making it worse.

As a result, we've started to look closely at a variety of data quality metrics to understand how they relate to the pace of patient recruitment. The results, while still preliminary, are encouraging.

Here is a plot of a large, recently-completed trial. Each point represents an individual research site, mapped by both speed (enrollment rate) and quality (protocol deviations). If faster enrolling caused data quality problems, we would expect to see a cluster of sites in the upper right quadrant (lots of patients, lots of deviations).

Click to enlarge: Enrollment and Quality

Instead, we see almost the opposite. Our sites with the fastest accrual produced, in general, higher quality data. Slow sites had a large variance, with not much relation to quality: some did well, but some of the worst offenders were among the slowest enrollers.

There are probably a number of reasons for this trend. I believe the two major factors at work here are:
  1. Focus. Having more patients in a particular study gives sites a powerful incentive to focus more time and effort into the conduct of that study.
  2. Practice. We get better at most things through practice and repetition. Enrolling more patients may help our site staff develop a much greater mastery of the study protocol.
The bottom line is very promising: accelerating your trial’s enrollment may have the added benefit of improving the overall quality of your data.

We will continue to explore the relationship between enrollment and various quality metrics, and I hope to be able to share more soon.

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