Health Business Blog

Health care business consultant and policy expert David E. Williams share his views

Pharma has trouble recruiting patients for trials –could excessive exclusion criteria be the reason?

This month’s R&D Directions has an article about the difficulty pharmaceutical companies have in recruiting patients for their trials. The article suggests that the problem may lie with trial sponsors that have not thought through their recruiting strategies, and with patients who are scared about side effects and product withdrawals.

I can think of a few more reasons:

  • Trial protocols often have long lists of exclusion criteria. These criteria make recruiting difficult and if anything they harm the results. For example, an article by Posternak et al. in the American Journal of Psychiatry 159:2, said, “Many of the standard exclusion criteria currently used in antidepressant trials may not be achieving their goals of maximizing drug-placebo differences. The practice of excluding subjects with particular clinical profiles, which greatly reduces the generalizability of antidepressant efficacy studies, appears to lack empirical support.”
  • Some sponsors are disorganized and difficult for sites to work with. Leading sites have more trials than they can handle and will favor enrolling patients in the trials that are easier to run
  • Some of the trials are mainly for marketing purposes. It’s not necessarily in a patient’s best interest to enroll. Contrary to popular belief, well-informed patients are not necessarily the most interested in enrolling in trials

Predictive modeling meets reality

Predictive modeling is an emerging discipline that health plans use to identify members who are likely to become ill soon and are therefore likely to cost the plan a lot of money. The objective is to manage these patients prospectively to minimize expensive events and conditions. Predictive modeling isn’t trivial –it involves data scrubbing and sophisticated data mining.

But it turns out that making accurate predictions is only half the battle. According to Howard Brill, manager of medical informatics at Monroe Plan for Medical Care, Inc., as quoted by the Healthcare Intelligence Network:

One of the major challenges we’ve had is communicating what that information means to our nurse case managers. There is a very strong pull by nurse case managers to focus attention on the sickest patients. These are not necessarily the individuals on whom they have the greatest impact.

It’s another example of how a systematic approach is necessary to achieve cost and quality improvements. Well intentioned individuals acting in a vacuum or sophisticated modeling techniques aren’t effective on their own.

800 pound gorillas can be friendly

Today’s Arkansas Democrat-Gazette has an article that explores the implications of having the local Blue Cross Blue Shield plan dominate the market, as is the case in Arkansas. (Blue Cross posts hot ’04, but rising costs stalk field, by Brian Baskin.) I’m quoted as saying that while it’s important to keep an eye on the Blues to avoid excesses, there are some positive aspects. I’ve seen high-share Blues do a number of innovative things, including BCBS of Massachusetts’ subsidies for e-prescribing and sponsorship of the Massachusetts eHealth Collaborative. A number of Blues are promoting online doctor-patient messaging. Why is this?

  • In healthcare, only payers with high market share have the power to drive innovation. We see this most starkly in single payer, socialized systems such as the UK, where the National Health Service has driven innovation in electronic medical records, electronic prescribing, and pay-for-performance to a much greater degree than has occurred in the US
  • Government monopolies, such as Medicare, Medicaid, and the VA System, despite all their flaws, have shown themselves capable of leading and sustaining innovation. Private payers usually adopt Medicare’s ideas
  • Healthcare is mainly a local business, so national companies such as Aetna, Cigna, United, and Humana are usually fairly unsuccessful at eroding local Blues’ shares, as long as the local Blue is providing reasonable service

FDA is gunning for Neurontin

The FDA is asking makers of anticonvulsants to re-examine their clinical trial data to see if the drugs increase suicide risk. This is the same path that led to the placement of black box warnings on all antidepressants, making doctors warier about prescribing them.

Pfizer’s Neurontin is the leading drug in the class, and is also the poster child for overly aggressive pharmaceutical market expansion efforts and dubious post-marketing research. As the Boston Globe notes, Pfizer’s Warner Lambert division recently paid $430 million in fines for illegally marketing Neurontin “for illnesses ranging from migraines to hiccups.”

It’s one thing to tolerate rare but serious risks in the treatment of major illnesses such as epilepsy and bipolar disorder. But the same level of risk is unacceptable for hiccups. By marketing overzealously to people with minor illnesses who don’t need their drugs, the industry has put itself in danger of having its products removed from the shelves. As I’ve written recently, that’s what appears to have happened with Vioxx and Bextra, and there’s a real risk of the same thing happening with asthma drugs.

It’s a real shame for the seriously ill patients who depend on these drugs. Rather than seeing drugs pulled from the market, I’d like to see physicians step up and take a more skeptical view of what they hear from drug reps.