That’s evidence the randomized clinical trial system works, USF researcher reports in Nature

USF Distinguished Professor Benjamin Djulbegovic, MD, PhD, has studied the ethics of randomized clinical trials and their effectiveness in evaluating the outcomes of new treatments for decades.

Now, in a paper published Aug. 22 in the top journal Nature, Dr. Djulbegovic and colleagues report that on average new treatments work better than existing ones just over half the time. On scientific and ethical grounds, they say, the randomized controlled trial (RCT) system’s little more than 50-50 success rate over the past half century is evidence that the system is working as intended.

The researchers analyzed 860 phase III published and unpublished RCTs performed by academic institutions or pharmaceutical companies.  These trials collectively involved more than 350,000 patients. 

“Our retrospective review of more than 50 years of randomized trials shows that they remain the ‘indispensable ordeals’ through which biomedical researchers’ responsibility to patients and the public is manifested,” the researchers conclude. “These trials may need tweak and polish, but they’re not broken.”

Dr. Benjamin Djulbegovic

People who consent to participate RCTs are willing to be randomly allocated to new or existing treatments.  While RCTs are considered the gold standard for comparing the effects of one treatment to another, the gradual progress they yield can seem frustratingly slow — particularly for patients with poor standard treatment options.

Yet, the genuine uncertainty associated with individual RCTs has been vital to the gains in therapeutics, said Dr. Djulbegovic, professor of medicine and oncology at the USF Health Morsani College of Medicine and Moffitt Cancer Center.  If there was significant likelihood that one treatment in a comparison was better than the other, it would be unethical to deny some patients the superior treatment, and well-informed patients would probably refuse to participate in the study, he said.

Incremental advances in treatment generated by RCTs over time – such as childhood leukemia cure rates moving from zero to 80 percent even though only 2 to 5 percent of new treatments provided a breakthrough – have translated into important improvements in health and lifespan, the authors say.  However, they suggest trials could still benefit from more rigorous design, implementation and reporting –with widespread publication of trial results, including negative findings.

The Nature paper is one of a series of publications that Dr. Djulbegovic and colleagues have authored this year (25 so far), including a clinical therapeutics case study in the New England Journal of Medicine.

Article citation:
“Medical research: Trial unpredictability yields predictable therapy gains;”  Benjamin Djulbegovic,Ambuj Kumar, Paul Glasziou, Branko Miladinovic^, and Iain Chalmers, Nature, August 22, 2013, pp 395-96.

Tampa, FL (May 23, 2013) – The Patient-Centered Outcomes Research Institute (PCORI) has approved a $2.1-million award to the University of South Florida College of Nursing to study “Patient Outcomes of a Self-care Management Approach to Cancer Symptoms: A Clinical Trial.” USF Distinguished Professor and Thompson Professor of Oncology Nursing Susan C. McMillan, PhD, ARNP, FAAN, will lead the research project.

The USF College of Nursing project will test a brief intervention, known as COPE, which aims to teach cancer patients management skills for improving symptoms they identify as the highest priority.

“Improving cancer patients’ ability to self-manage difficult symptoms may diminish patient suffering, improve quality of life, and decrease emergency room visits and associated healthcare costs,” Dr. McMillan said. “We hope that this intervention will be as successful for patient self-care as it has been when implemented with caregivers of hospice patients with cancer.”

The USF College of Nursing study is one of 51 new awards by PCORI, totaling $88.6-million over three years, to fund patient-centered comparative clinical research effectiveness projects.  It is part of a portfolio of projects that address PCORI’s national research priorities and will provide patients with information to help them make better informed decisions about their care.

The only other new PCORI award in Florida went to the college’s clinical collaboration partner Moffitt Cancer Center to study a navigator-guided psychoeducational intervention for prostate cancer patients and caregivers.  Richard Roetzheim, MD, professor of family medicine at the USF Health Morsani College of Medicine, is one of the investigators for the Moffitt study.

Susan McMillan, PhD, is lead investigator for the USF Collge of Nursing’s newly awarded PCORI project.

The randomized clinical trial led by Dr. McMillan will evaluate the effectiveness of COPE in alleviating moderate to high-intensity cancer symptoms causing distress, frequency or interference with patients’ lives. To conduct the study, the researchers will recruit 300 cancer center outpatients with breast, colorectal, lung and prostate cancers

 “At the University of South Florida, the College of Nursing is conducting groundbreaking research to improve the health of patients, families and our community,” said Dianne Morrison-Beedy, PhD, RN, WHNP-BC, FNAP, FAANP, FAAN, senior associate vice president of USF Health, and dean of the College of Nursing. “At Nursing we are transforming healthcare and transforming lives – working with our healthcare partners locally, regionally and nationally to make life better.”

All the PCORI projects were selected through a highly competitive review process in which scientists, patients, caregivers, and other stakeholders helped to evaluate more than 400 applications for funding. Proposals were evaluated on the basis of scientific merit, how well they engage patients and other stakeholders, their methodological rigor, and how well they fit within PCORI’s national research priorities.

 “This project reflects PCORI’s commitment to support patient-centered comparative effectiveness research, a new approach to health research that emphasizes the inclusion of patients and caregivers at all stages of the study process,” said PCORI Executive Director Joe Selby, MD, MPH. “The research will provide patients and those who care for them better information about the healthcare decisions they face.”

“The vision of PCORI — that “patients and the public have the information they need to make decisions that reflect their desired health outcomes” — is highly aligned with the College of Nursing, where we focus on research that improves health,” said Cindy L. Munro, PhD, RN, ANP-BC, FAAN, USF College of Nursing professor and associate dean for research and innovation at the USF College of Public Health. “We are very proud that Dr. McMillan’s research has been selected for funding by PCORI.  Her work will not only benefit patients, but also serves as a model for research excellence in the College and beyond.”

Through the Center for Living with Chronic Illness, the USF College of Nursing focuses the research expertise of its nurse scientists, faculty and students as they collaborate on unique solutions to the nation’s leading health care problems, such as heart disease, Alzheimer’s disease and cancer.

The latest awards were part of PCORI’s second cycle of primary research funding. All were approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.  This new round of funding follows PCORI’s initial approval of $40.7 million in support for 25 projects under the institute’s national research priorities

For more information about PCORI’s funding announcements, visit www.pcori.org/funding-opportunities.

-USF Health-

USF Health’s mission is to envision and implement the future of health. It is the partnership of the USF Health Morsani College of Medicine, the College of Nursing, the College of Public Health, the College of Pharmacy, the School of Biomedical Sciences and the School of Physical Therapy and Rehabilitation Sciences; and the USF Physician’s Group. The University of South Florida is a global research university ranked 50^th in the nation by the National Science Foundation for both federal and total research expenditures among all U.S. universities. For more information, visit www.health.usf.edu.

 -About PCORI-

The Patient-Centered Outcomes Research Institute (PCORI) is an independent, non-profit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers and clinicians with the evidence-based information needed to make better-informed health care decisions. PCORI is committed to continuously seeking input from a broad range of stakeholders to guide its work. More information is available at www.pcori.org.

Media contact:
Ashlea Bailey, USF College of Nursing Communications
(813) 396-9642, or ahudak@health.usf.edu