VA tries new method for treatment comparison trials.   

By Deborah Borfitz 

August 15, 2011 | A new type of clinical trial now undergoing testing at the Veterans Affairs (VA) Boston Healthcare System will likely be of interest to emerging accountable care organizations (ACOs) as well as the drug companies that court them. The new approach, most useful in comparative effectiveness research, overcomes the chief disadvantages of the two flanking options: an observational study involving non-experimental treatment decision making or a full-scale, randomized and placebo-controlled trial. 

So says Stanford University biostatistician Philip Lavori, who developed the fledgling “point-of-care” clinical trial with the help of Boston clinicians and researchers. The current choices are to get a right but possibly outdated answer (think the $125 million Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) or a cheap and fast one with some potentially unpleasant surprises (i.e. increased heart disease and breast cancer risk among women given hormone replacement therapy).

Point-of-care trials couple the best features of the alternatives by making comparative effectiveness research a good “ecological fit” with routine patient care while getting rid of confounding effects via randomization, says Lavori. Clinicians decide at the point of care if there is a strong reason to prefer one course of treatment over another. If one option seems just as good as another, they can invite the patient to participate in a clinical trial that randomly makes the decision for them.

Popularity of the new approach will depend on overcoming a few technical hurdles, says Lavori, not the least of which is decision support infrastructure that ties together electronic medical records and clinical outcomes. Not many patient care organizations, outside of the VA and Kaiser Permanente, have that level of information technology (IT) maturity. Then there’s the question of how to handle human subject protection. The conventional informed consent process seems like time-devouring overkill for trials involving approved therapies that merely change the randomizer from clinician to machine. But institutional review boards would need to okay any simplification of the informed consent process.

At the moment, point-of-care clinical trials have only one use case among a select group of Boston-area veterans, notes Lavori. The VA facility there is comparing two standard methods of treating hospitalized diabetics: short-acting insulin several times a day with dosing based on blood sugar levels, planned activities, and sugar consumption or longer-acting insulin throughout the day in doses based on their weight. Patients have been enrolling in the study since October 2010.

The VA will roll out point-of-care trials to some of its other facilities over the next six months, says Lavori. Trials will initially involve insulin dosing only but then expand, possibly to include treatment of post traumatic stress disorder and contrast agents used in angiography.

The health care landscape could well morph into something more VA-like in the near future, where information technology behind the scenes supports trial randomization as well as informed consent. “This isn’t rocket science,” says Lavori, adding that the sociological hurdles surpass the technical ones. The IT gurus tasked with keeping an organization’s clinical systems humming must be convinced of the “value and safety” of running trial-related programs in the background. Electronic medical records systems like Epic also need to see the business wisdom in building those types of modules.

Given the rise of ACOs and millions of federal dollars being poured into comparative effectiveness research, that day could come sooner rather than later. “ACOs have a tremendous business incentive to do the right thing with patients” in terms of cost and outcomes, says Lavori. “They’ll be in the comparative effectiveness business.” Most of them, he presumes, will see the advantage of conducting research on the local patient population whose care outcomes are tracked and linked to reimbursement.

Industry sponsors may not have a good business incentive to engage in comparative effectiveness research, but that doesn’t necessarily mean point-of-care clinical trials will be irrelevant to them, says Lavori. Sponsors will eventually have to forge relationships with ACOs. And they’re already well attuned to the spending behaviors of third party payers. “Comparative effectiveness research will become more important for drug companies to address because they have to compete in the marketplace if there are [treatment] alternatives, as there are now.”

Point-of-care trials will be of use in branches of comparative effectiveness research not always recognized as such, notably personalized medicine, says Lavori. Researchers engaged in breast and ovarian cancer trials have already expressed an interest in the new method.