With the advent of healthcare reform and the renewed emphasis on controlling costs comes an increased emphasis on comparing treatment options from a variety of factors. These factors were examined by seven speakers on May 17 during C5 “Comparative Effectiveness Research: Why Now?”

“We have an absolutely formidable biomedical research enterprise that has done a nice job in drug discovery and treatment discovery, and we now know what works in research settings. The challenge for the future is how we make sure the investments that have been made to date actually reach patients and improve the outcomes of real-world patients,” said Jerry Krishnan, MD, PhD, associate professor of medicine and epidemiology, and director of the Asthma and COPD Center at the University of Chicago.

Dr. Krishnan began the symposium by discussing what comparative effectiveness research (CER) is, providing the context for other speakers, who discussed research in specific areas, including asthma, critical care, sleep disorders and COPD. The program also highlighted these topics from the point of view of patients.

“The challenge for us is that we have an enormous pipeline of strategies for care that we know work in research settings, and we need to get it to the actual point of care where patients and doctors are making healthcare decisions,” he said. “Healthcare decision-makers also include insurers and policy makers, and we need to engage the broader community as we think about how best to get it out there to improve the outcomes of patients.”

Dr. Krishnan said he hoped the symposium would raise the awareness of additional complementary research questions and research opportunities. “As researchers, we need to do a better job of messaging that this is also an important part of our research spectrum, and we need to be active in those areas as well,” he said.

CER is part of the research spectrum, which also includes efficacy research, which asks, “Can it work?” and effectiveness research, which asks, “Will it work?” he said. “This isn’t about which is better. This is about complementing each other, but the questions are quite different.”

CER is underdeveloped in the United States because its healthcare infrastructure does not easily support collaborations between stakeholders who generate, disseminate and use new knowledge, Dr. Krishnan said. Stakeholders include patients, families, clinicians, professional organizations, payers, policy makers, regulators, funding agencies and researchers.

However, there is public support for CER, as seen through the establishment of the Effective Health Care Program, the American Recovery and Reinvestment Act (ARRA) and the Patient Protections and Affordable Care Act (ACA). The ARRA jumpstarted CER with $1.1 billion in funding in 2009, and the ACA established the Patient-Centered Outcomes Research Institute (PCORI), which offers $500 million annually in CER research.

“The NIH, including the NHLBI’s Division of Lung Diseases, is well positioned to take advantage of these new opportunities. Today, we are ensuring that the research community is aware of these growing opportunities that exist,” Dr. Krishnan said.

European Perspective
While CER may be underdeveloped in the U.S., it is more established in Europe, said Jorgen Vestbo, DrMedSci, of Hvidovre Hospital at the University of Copenhagen, and the Respiratory Research Group at the University of Manchester, U.K.

Northern European nations primarily have national health service systems that are very aware of the costs of research and treatment compared with the insurance-based system of the U.S. “There is a huge difference in how we spend money,” Dr. Vestbo said, later adding, “Cost-saving guidance is not about restricting treatment, it is about cost-effectiveness.”

As a result, CER is increasingly used by European health authorities for evaluation of drugs and drug reimbursement, he said. Also, costs are increasingly being incorporated into the evaluation of drug effectiveness and the European CER experience cannot be directly transferred to the U.S. because of significant political differences and cultural attitudes.

Patient Perspective
Presenting a patient’s perspective, with a focus on costs, was John Walsh, president of the COPD Foundation.

“Patients care about two things: survival and quality of life,” Mr. Walsh said. “We do have real concerns about costs, whether it is co-pays or co-morbidities. We are concerned about costs as it relates to having access to therapies to treat us.”

Patients want to be seen as stakeholders in the research process, “to enhance the credibility and usefulness of studies,” he said. In addition, the perspective of CER versus cost must be clarified, and results—with solutions—must be reported back to patients.

“We need to build trust, that is the critical part,” Mr. Walsh said. “Patients must be part of the solution, and we must trust that CER research is in our best interest and not just about the bottom line.”

CER in Asthma Research
CER is the basis of an asthma study, “Effectiveness of Low-dose Theophylline as Add-on Therapy in the Treatment of Asthma (LODO),” which was discussed by Robert A. Wise, M.D., professor of medicine at Johns Hopkins University School of Medicine.

The study asks the clinical question: Are asthma patients with suboptimal control better treated with low-dose theophylline or oral montelukast? The use of montelukast costs $1,824 a year, compared with $116 for generic theophylline, he said. Overall, there is little difference in outcomes, but a subgroup of patients on inhaled corticosteroids saw significant improvement on theophylline.

Another treatment that is “low-hanging fruit” in CER in asthma is bronchial thermoplasty for patients with severe asthma that is not well controlled. The procedure costs $12,000 to $18,000, but it is associated with a 32-percent reduction in asthma attacks and a 73-percent reduction in emergency room visits, Dr. Wise said.

The potential impact could save billions of dollars annually. Ten percent of asthmatics are eligible for the procedure, and the potential cost savings is estimated at $3.6 billion to $7.1 billion a year. Over 10 years, the cost savings would be $36 billion to $71 billion, while the cost of treatment is $9 billion, he said, adding, “The impact would be enormous.”

Critical Care Research
In critical care, CER often may not play a role because of the unique needs of critical care patients who may not respond well to trials, said Gordon R. Bernard, M.D., associate vice chancellor for clinical and translational research, and Melinda Owen Bass Professor of Medicine at Vanderbilt University.

As an example, he looked at the treatment of acute respiratory distress syndrome and severe sepsis in 1980. Tidal volumes of 12-15 ml/kg and high airway pressures were ignored, but the Respiratory Management in Acute Lung Injury (ARMA) low tidal volume trial demonstrated a substantial mortality benefit, Dr. Bernard said.

“A CER version of the same comparison seems unlikely,” he said, adding, “An effectiveness trial using a range of tidal volumes, e.g. four versus six versus eight, would be practical and ethical.”

Sleep-Disorder Studies
Looking at the potential of using CER in sleep-disorder studies was Susan Redline, MD, MPH, Peter C. Farrell, MD, professor of sleep medicine and director of programs in sleep and cardiovascular medicine and sleep medicine epidemiology at Brigham and Women’s Hospital and Beth Israel Deaconess Medical Center at Harvard Medical School.

An area that holds potential for CER is sleep apnea, because it is a significant predictor of hypertension and cardiovascular disease. The cost of obstructive sleep apnea (OSA) being untreated in the U.S. is $3.4 billion a year. Among the critical questions that could be studied in this area using CER are if treatment of OSA could prevent or reduce heart failure, stroke, hypertension and diabetes, she said.

“There are clear opportunities for CER to look at comparative therapies, as well as look at other effects,” Dr. Redline said, adding that is would also help to look at efficacy and effectiveness research in sleep apnea.

COPD Research
Another possible use of CER could be the study of the use of IV versus oral steroids in COPD patients, said Richard Mularski, MD, MSHS, MCR, of the Center for Health Research, Kaiser Permanente Northwest and clinical assistant professor of medicine in the Department of Pulmonary and Critical Care Medicine at Oregon Health and Science University.

“Here lies an opportunity for CER within linked registries … enabling ongoing surveillance of care quality and patient outcomes …[they] can be used to track changes in practice, patient adherence, as well as benefits and harms in real-world settings,” Dr. Mularski wrote in a Journal of the American Medical Association opinion piece.