AHRQ Comparative Study Agenda Should Emphasize Lit Reviews – McClellan

The federal government's investment in comparative effectiveness research for drugs should emphasize literature reviews and other alternatives to clinical trials, Centers for Medicare & Medicaid Services Administrator Mark McClellan said.

"We're going to need to find better approaches to generate medical evidence in a way that is rigorous, that provides meaningful results, but that doesn't have to take so many years and cost so much money every time," McClellan told an Agency for Healthcare Research & Quality "town hall" meeting in Washington, D.C. May 21. "This includes more systematic reviews of existing literature."

The Medicare Rx law directs AHRQ to develop a comparative research agenda; an initial priority list is due by June 8 (¹ (Also see "AHRQ Outcomes Research Should Focus On Diseases, Not Drugs – PhRMA" - Pink Sheet, 24 May, 2004.), p. 25).

"The 'gold standard' for developing clinical evidence remains the randomized trial," McClellan noted, "but to accurately detect differences between treatments, these approaches need to enroll very many patients and can take a fair amount of time."

"Don't Jump To Clinical Trials"

"Clearly, we're not going to get very far very fast if we have to spend tens - if not hundreds - of millions of dollars every time we need to answer questions about the comparative benefits of better treatments. Nor can we settle for under-funded, underpowered studies that end up being too weak to detect a real difference," McClellan said.

Other speakers echoed McClellan's call for a more efficient use of resources.

"Don't jump to clinical trials themselves before you've done the systematic reviews that will help set priorities and help you design, implement and make findings of clinical trials further down the road," Lewin Group Senior Scientist Clifford Goodman said.

Data collected from other programs mandated under the Medicare prescription drug law will also contribute to the comparative research database, McClellan said.

For example, through the chronic care improvement pilot program, "we're setting up a system to collect clinical information, including some important clinical outcome measures," McClellan said.

CMS will award disease management contracts starting in December (² (Also see "Medicare Chronic Care Projects Likely To Meet 5% Savings Goal, Rep. Says" - Pink Sheet, 17 May, 2004.), p. 20).

"Since beneficiaries in this program will be heavy users of medical care," the program will include "evaluation of about 30 mil. claims worth of data in addition to the clinical information measures," McClellan said.

Disease Management Pilots

The demonstration projects should provide "a pretty robust clinical database that we intend to use to generate good studies about what approaches to chronic care improvement work well, and which provide what benefits, and what their implications are for cost."

"This is a system that's going to be part of our business model," McClellan said. "It's building on data that we already collect as part of our claims system."

The demonstration project to cover oral drugs under Medicare Part B will also contribute to comparative data. "We will be using those same kinds of principles there to see what medication approaches work and what their consequences are."

In addition, electronic prescribing systems mandated by the Medicare Rx law can be used to collect outcomes data, McClellan suggested (³ (Also see "E-Prescribing To Improve Postmarketing Studies, CMS’ McClellan Predicts" - Pink Sheet, 19 Apr, 2004.), p. 24).

"We are taking steps with the implementation of the new law to encourage electronic prescribing, electronic health systems that will give us an even greater capacity to analyze clinical data and other data relevant to cost and outcomes in our patient population, including our big existing databases," the CMS administrator said.

"FDA Can Help"

FDA and other HHS agencies can also help leverage comparative research resources, McClellan said.

"It's not going to be an AHRQ effort or a CMS effort or an NIH effort, but we're all going to be working together."

"FDA can help, as well," McClellan said. FDA has "a lot of expertise on understanding what is known and what isn't known about many therapies," he added.

Acting FDA Commissioner Lester Crawford, who took over as head of the agency when McClellan moved to CMS, told a recent Wall Street conference that he believes Congress will one day give serious consideration to expanding FDA's mission to encompass cost-effectiveness (⁴ (Also see "FDA Will Be Given Cost-Effectiveness Role, Acting Commissioner Predicts" - Pink Sheet, 5 Apr, 2004.), p. 3).

The National Institutes of Health is "engaged in some steps to reduce the cost" of large comparative trials and to "improve the connection in the clinical trials that they support to questions that we need answered," McClellan said.

National Heart, Lung & Blood Institute Acting Director Barbara Alving, MD, told the AHRQ workshop that NIH is stepping up its efforts to align its research agenda with broader HHS policy priorities.

NIH Role Beyond ALLHAT

NIH is "working more closely with CMS" and FDA to keep the agencies apprised of "drugs under study" and "outcomes of our trials at a very early stage," particularly with therapies "that might result in coverage decisions," Alving said.

Alving noted that NHLBI headed up a head-to-head study of antihypertensives (ALLHAT) that could have a significant impact on the market for blood pressure lowering drugs (⁵ (Also see "ALLHAT Study Brings Calls For Comparative Trials, Greater Focus On Costs" - Pink Sheet, 23 Dec, 2002.), p. 13).

McClellan, however, pointed out that the ALLHAT study "took many years to finish" and carried a price tag of about $125 mil.

However, he added, NIH has other tools it can use to help develop more comparative information.

"For example, the National Cancer Institute's clinical trial network already has electronic data capabilities that it's using in conjunction with the FDA approval process," McClellan said.

That "will make the approval process and evaluation of evidence on treatments that have not yet come to market more quick and more predictable and less costly," McClellan said.

AHRQ Director Carolyn Clancy suggested that NIH and other federal agencies will be more important further down in the comparative research agenda.

"The first phase is going to focus a lot on systematic reviews and research syntheses, and that initial list has to be submitted to the Congress in a report in December of 2005. I think that's when we are particularly going to be turning to our other partners" at HHS "for help with solutions," Clancy said.

Health Canada Is Possible Partner

McClellan suggested partnering with other agencies, such as the Veterans Administration, or private sector payors that are conducting comparative effectiveness research.

"Many health care purchasers, from public sector purchasers like the VA to private employers and health plans, are increasingly conducting studies of comparative effectiveness of different ways of treating costly and common health problems," he said.

A comparative research agenda could be informed by similar research at the VA or even Health Canada, National Breast Cancer Coalition President Fran Visco told the forum. "Canadian health institutes and organizations...seem to be putting together very good models that could be followed, or could be looked at, at least, to see what parts are working and appropriate," Visco said.

"We need to further build upon the collaborations that we have, domestically and internationally, to develop this evidence and fill in the gaps in evidence as well," McClellan said.

"Confident" About Funding

AHRQ was authorized $50 mil. for comparative research under the Medicare Rx law, but funding was not included in the President's fiscal 2005 request.

"The open question is whether there's any resources freed up in 2005," Clancy said. "I'm quite confident there will be resources in 2006." Funding "is coming," McClellan concurred. There is support for a $75 mil. appropriation for comparative research in fiscal 2005 in the Senate (⁶ (Also see "Generic Biologics Approval Process Is Focus Of Employers’ Coalition" - Pink Sheet, 10 May, 2004.), p. 33).

Regardless of funding, "we have to move ahead anyway. The law requires that," Clancy said. "We will do as much as we can within existing resources."