The Skeleton in the Closet

What’s the biggest problem in conducting clinical trials today? That question would make for a lively debate! Readers of this column will assume I will point to data cleaning, or trials management. But there is a skeleton in the Clinical Operations closet, a problem we all have but rarely do much about. It’s an insidious cause of delay, enormous financial cost, frustration and inefficiency. I’m talking about patient recruitment.

Every one of you know patient recruitment problems wreak havoc on nearly every clinical program. In a survey conducted by our company, executives reported at least 50% of their trials encountered “significant” delays, with an average delay of 110 days ¡© nearly four, costly, months. Obviously, the more complex the protocol, the more rare the disease, or more broad the claims sought to be proved, the situation gets worse.

What was distressing in our research was the almost universal lack of proactive planning at sponsors to anticipate patient recruitment problems and the appropriate interventions to correct them. Nearly everyone admitted that recuitment problems were treated exclusively in “rescue mode”, in a crisis mindset. And yet, going in, we already know we’re going to have problems half the time.

A Growing Problem

Patient recruitment is likely to become an even bigger challenge in the near future because of:

the huge increase in drug candidates to be tested, driven by improved discovery techniques and genomics (“gene-tailored” drugs are likely to mean that multiple variants of the same compound need trials, on populations genetically screened)

a continuing increase in the number of trials, number of patients, and complexity of trials per compound, driven by global registration, multiple indications, drug interaction concerns, and the seeking of a competitive labeling edge

more and more players (SMOs, enrollment consultants, AMCs, managed care, CROs) seeking to mine the same well-known pool of patients

more and more compounds tackling new, harder-to-reach patient populations.

Diffuse Responsibility

Aggravating this problem is the diffuse responsibility for patient recuitment. When it comes to data cleaning problems, for better or worse most companies can point to their data manager and demand an answer. In many companies,

the responsibility for the performance of patient enrollment is diffuse, in the hands of managers with many other responsibilities of which enrollment is just one. Indeed, many players may get involved in helping (or not) with patient enrollment, which leads to lots of “helpers” but no single accountability.

Public Controversies

Another compounding factor, perhaps short-term or cyclical, is the recent media publicity about possibly inappropriate incentives for investigators to accelerate patient participation in clinical trials. Although the obvious ethical violations reported are reprehensible, they represent a very small proportion of trial experiences. But this public scrutiny is likely to make more skittish the pharmaceutical customer who is already under-utilizing initiatives to accelerate enrollment.

Public controversy over the privacy of patient records is also likely to dampen enthusiasm (at least publicly) for the mining of patient databases for proactive patient recruitment. But this public debate will also likely help define the conditions under which such research is acceptable, which in the end will make the use of such resources easier and more accepted.

Today’s Inadequate Solutions

The methods for improving enrollment turned to in rescue mode by most pharmaceutical companies are first, financial incentives, and second, various forms of advertising. Begun when the crisis is already in full bloom, these initiatives are inefficient by definition. While sophisticated advertising (the type of intervention most commonly thought of and offered when people think “patient recruitment services”) can play an important role in reaching and motivating potential subjects in a responsible manner, these media approaches address only the last of four steps to improving patient recruitment:

First, design a protocol with a realistic chance of enrollment!

Second, pick sites who have proven they can recruit effectively

Third, know who the sites’ patients are and reach out to those who are appropriate, and

only Fourth, motivate appropriate candidates as required.

The Role of Information Technology

Well, what does this have to do with technology? A lot, as it happens. In the earliest stages of the problem, the new computer-based intelligence being applied to protocol design in various approaches may be very helpful. There are much simpler uses of technology that can help here, however; for instance, using groupware to distribute, edit, iterate and close quickly on the protocol outline. This in itself, with very little cost, reduce weeks from clinical development time.

Patient recruitment problems reinforce the Site-Centric view (as distinct from the CDM-Centric view) of clinical trials data processing that this column has continually advocated. By getting closer to your sites in all ways, including through data, you can gain confidence in and improve their ability to execute the recruitment plan. In turn, sites who concentrate on building tighter connections to their patient community (instead of on acquiring each other), will be more useful to the industry.

Information technology is the obvious underpinning of both of these points — getting to know in a meaningful, evaluative way, which investigators can responsibly deliver on what they promise; and knowing your patients well enough to use highly cost-effective outbound calling to contact interested subjects likely to meet the trial criteria. For instance, if you simply tapped the knowledge within your company (in a quick and timely fashion!) about the performance of investigators you yourselves have used, you can fight off that product manager who insists on using the high-profile thought leader with the terrible enrollment record.

In the near future, the industry will be putting great energy into figuring out how to responsibly use existing patient databases. And the Internet, while so far quite disappointing, according to our research, in having a meaningful impact on trial recuitment, does promise exciting possibilities as disease communities and other virtual patient pools form on the Web.

Patient recruitment is a source of at least as much delay as data cleaning. If you’ve got EDC on its feet and down the road, it’s time to pull this other skeleton out of the closet and acknowledge “yes, we have a problem.” It’s always the first step to recovery.