A series of new papers in the journal Lancet discussing how to increase value and reduce waste in research includes a contribution by USF Distinguished Professor Benjamin Djulbegovic, MD, PhD.

Dr. Djulbegovic, professor of medicine and oncology at the USF Health Morsani College of Medicine, was a co-author of one of five papers published Jan. 8 in the Lancet series: “How to increase value and reduce waste when research priorities are set.”

The article explains why decisions about which research to fund should be based on issues relevant to the users of research — including patients, clinicians and policy makers – and more systematically account for what researchers already know or are investigating.

“The Lancet series effectively points out that at least 50 percent of research investment is wasted, amounting to billions of dollars a year,” Dr. Djulbegovic said.

Benjamin Djulbegovic, MD, PhD

About $240 billion a year is spent globally on biomedical research.  While the enterprise has yielded substantial health improvements, only about half of the study results are made public for use by other researchers and doctors treating patients.  And, 40 to 89 percent of published trial studies could not be replicated – critical to validating study findings – because the interventions tested were poorly or incompletely described.

In their report, lead author Dr. Iain Chalmers, Dr. Djulbegovic and colleagues point out that good research ideas often produce unanticipated results and these disappointments should not be deemed wasteful as long as “the way in which these ideas are prioritized for research is transparent and warranted.”

Unexpected results are different from avoidable or unjustified waste, which encompasses inefficiencies in the way research studies are chosen, designed, conducted, analyzed, disseminated and reported. It includes the tendency not to report or publish negative study findings, which can be valuable in saving time and money by indicating when a drug or medical device does not work, or may even harm patients.

In their Lancet article Dr. Djulbegovic and co-authors make the following recommendations for reducing research waste:

–          Investigate ways to improve the yield from basic science research.

–          Be more transparent about how research funders decide which research to support, making clear how they take into account the needs of potential users of research.

–          Systematically assess existing evidence before investing in additional research.

–          Strengthen, develop and use sources of information about research already in progress, insist on publication of protocols at the beginning of studies, and encourage collaboration.

Four USF Health faculty members were among 11 recipients of the university’s 2013 Faculty Outstanding Research Achievement Awards.

Cesario Borlongan, PhD; Chad Dickey, PhD; and Benjamin Djulbegovic, MD, PhD, all of the Morsani College of Medicine;  and Wilbur Milhous, PhD, of the College of Public Health, joined awardees honored at an Oct. 28 awards luncheon hosted by the USF Office of Research and Innovation.

L to R: USF Senior Vice Provost Dr. Dwayne Smith, USF President Judy Genshaft, award recipient Dr. Benjamin Djulbegovic, and Dr. Paul Sanberg, senior vice president for research and innovation.

The annual awards both celebrate USF faculty members for publications, awards and grants exemplifying their outstanding scholarship and research and underscore the professional recognition that they attracted the previous calendar year from national and international peers. The USF System Research Council selects awardees based on an open competition.

Dr. Borlongan, professor and vice chair for research, neurosurgery and brain repair, and director of the Center for Aging and Brain Repair at the Morsani College of Medicine, was recognized for his research and scholarly work in translational biomedical research.  In 2012 he was elected a fellow of the American Association for the Advancement of Science based on his research on stem cell therapy for stroke. He published 23 peer-reviewed articles in journals such as PloS One and Stem Cells and Development, filed a patent application, and became principal investigator on two federal grants, a James and Esther King state grant, and co-investigator on a VA Merit award.

Cesar Borlongan, PhD, (left) and Chad Dickey, PhD

Dr. Dickey, associate professor of molecular medicine at the Morsani College of Medicine and USF Health Byrd Alzheimer’s Institute, was recognized for his research studies on the molecular mechanisms underlying neurodegeneration. In 2012, he published eight manuscripts in top journals: Journal of Biological Chemistry, Autophagy, Chemistry & Biology, ACS Chemical Biology, and Journal of Molecular Biology. Four papers focused on compounds that target members of the heat shock proteins family, which Dr. Dickey found to have therapeutic potential. This discovery has advanced knowledge of the biological mechanism used by the cell to deal with protein aggregates and led to the discovery of a leading drug candidate for treatment of Alzheimer’s disease.

Dr. Djulbegovic is a distinguished professor and director, Division of Evidence-Based Medicine and Health Outcomes Research, Department of Internal Medicine, Morsani College of Medicine. He was recognized for his work in 2012 on the development of two major theories in clinical research and decision-making:  the theory regarding treatment success in clinical trials and the acceptable regret theory.  His contributions include improving the practice of medicine using the following evidence-based medicine methods: predicting and proving the optimal treatment discovery rate, developing a new theory of medical decision-making, and improving patient outcomes and saving resources by generating evidence-based guidelines.

Wilbur Milhous, PhD

Dr. Milhous, professor of the Global Health Infectious Disease Research Program and associate dean of research, College of Public Health, was recognized for his research translating technology from the laboratory to the field. In 2012, Dr. Milhous was designated a distinguished alumnus from the University of North Carolina for his contributions to the discovery and development of drugs for neglected diseases.  He also completed a five-year appointment representing USF on the Advisory Committee of the Medicines for Malaria Venture (MMV), which holds the world’s largest research and development portfolio for new and innovative antimalarial medicines, and was appointed as an editor of Antimicrobial Agents and Chemotherapy, the leading journal for infectious disease drugs.

Group photo by Aimee Blodgett, University Communications and Marketing

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.

Researchers show that uncertainty about new treatments meets ethical requirements

On average, new treatments perform better in clinical trials only slightly more often than existing treatments, according to a new systematic review led Benjamin Djulbegovic, MD, PhD,  distinguished professor and associate dean of clinical research at the USF Health Morsani College of Medicine.

The fact that experimental treatments are not more effective may seem disappointing, but the authors of the review, published in The Cochrane Library, say their findings satisfy an important ethical requirement for clinical trials.

USF Health’s Dr. Benjamin Djulbegovic led the randomized clinical trials review published in The Cochrane Library.

Randomised trials compare the effects of one treatment to another. In a randomised trial patients are randomly allocated to different treatment groups to ensure that like will be compared with like. When a new treatment is being tested, it is hoped or even expected that it will be better than the established treatment with which it is being compared. These expectations lead to an ethical dilemma. If the researchers already know that one treatment is better, they would be knowingly allocating some people to an inferior treatment. If randomised trials are to be ethical, therefore, only half of new treatments should turn out to be better than existing ones.

Cochrane researchers looked at evidence from 743 publicly funded randomised trials involving 297,744 patients in total. The trials included new, experimental treatments for cancer and neurological disorders, as well as a range of other diseases. On average, only very slightly more than half of new treatments proved to be better than established treatments.

“When we compared the effects of new treatments to established ones, the pattern was almost symmetrical. This is good news, because it means researchers genuinely don’t know whether new treatments are going to be any better,” said Dr. Djulbegovic, who works at USF Health Clinical Research, and the H. Lee Moffitt Cancer Center & Research Institute, at the University of South Florida in Tampa, Florida, US. “So, overall, what we show is that we can expect the new treatments to perform better a little bit more often than established treatments, at least in publicly-funded trials like the ones we considered.”

The researchers found the same pattern in trials going back five decades. The results provide an answer to the question posed 15 years ago in the British Medical Journal by Iain Chalmers, a founder of the Cochrane Collaboration and one of the authors of the review.  “In 1997, in a letter published in the BMJ, I asked ‘What is the prior probability of a proposed new treatment being superior to established treatments?’ I think this review currently provides the best answer to that question,” said Chalmers.

Full citation: Djulbegovic B, Kumar A, Glasziou PP, Perera R, Reljic T, Dent L, Raftery J, Johansen M, Di Tanna GL, Miladinovic B, Soares HP, Vist GE, Chalmers I. New treatments compared to established treatments in randomized trials. Cochrane Database of Systematic Reviews 2012, Issue 10. Art. No.:MR000024. DOI: 10.1002/14651858.MR000024.pub3.

About The Cochrane Library
The Cochrane Library contains high quality health care information, including the Cochrane Database of Systematic Reviews, from the Cochrane Collaboration. Cochrane Systematic Reviews bring together research on the effects of health care and are considered the gold standard for determining the relative effectiveness of different interventions. The Cochrane Collaboration (http://www.cochrane.org) is a UK registered international charity and the world’s leading producer of systematic reviews. It has been demonstrated that Cochrane Systematic Reviews are of comparable or better quality and are updated more often than the reviews published in print journals (Wen J et al; The reporting quality of meta-analyses improves: a random sampling study. Journal of Clinical Epidemiology 2008; 61: 770-775).

In June 2012, the Cochrane Database of Systematic Reviews received an impact factor of 5.715, from Thomson ISI, placing it in the top ten general and internal medicine journals.

 The Cochrane Library is published by Wiley on behalf of The Cochrane Collaboration.

 The Cochrane Library Podcasts: a collection of podcasts on a selection of Cochrane Reviews by authors of reviews in this issue will be available from www.cochrane.org/podcasts.

 Accessing The Cochrane Library
The Cochrane Library can be accessed at www.thecochranelibrary.com. Guest users may access abstracts and plain language summaries for all reviews in the database, and members of the media may request full access to the contents of the Library. For further information, see contact details below. A number of countries, including countries in the World Bank’s list of low- and low-middle income economies (countries with a gross national income (GNI) per capita of less than $4700), have national provisions by which some or all of their residents are able to access The Cochrane Library for free. To find out more, please visit www.thecochranelibrary.com/FreeAccess.