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.
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.