You’re shopping for, let’s say, shampoo. There are two products on the shelf. They claim to do the same thing. One, we’ll call it ‘Cheapsuds’, is from the basics range; the other, ‘Goldlocks’, a high-end product, forty times more expensive. The companies making them are owned by the same parent company and it’s clearly in their interests to persuade you to buy the more expensive one. If you do this, you’re going be facing a hefty bill, so you’re going to want to know how they compare in terms of how well they work and whether they might do you any harm.
Now, the company isn’t going to help you out here. You’d be right to be a bit wary about the claims they make for the products, based on research they’ve sponsored. There’s the added complication that Cheapsuds started life as a handwash, very similar to Goldlocks and much cheaper, but is it ok to use it on your head? Top stylists can’t agree and many worry that Cheapsuds may be harmful when used in this way. What you urgently need, to make a choice that is right for your purse and your hair, is some independent, reliable research comparing these products.
Now here’s the science!
How much more important this would be if we were talking about medicines. Well we are. This happens in health care too and this is the story behind two medicines for an eye disease affecting around 3% of people aged over 65, age-related macular degeneration (AMD). At the heart of it is a lot of money, vested interests versus independent research, and the Refers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of a lot of people.
Two drugs, ranibizumab (brand name Lucentis®) & bevacizumab (Avastin®), are prescribed for macular degeneration. They’re closely related and thought to have similar benefits, but only ranibizumab is licensed for this use. Bevacizumab was developed as a cancer treatment but is sometimes used, at a much lower dose, to treat AMD, though its off-license status has restricted this in many countries. Most of the disagreement about the two drugs focused on their systemic (whole body) safety. A single dose of ranibizumab costs about the same as forty doses of bevacizumab, so the cost implications are huge. It is vital to know whether they are equally safe and now a new Cochrane review comparing them in terms of serious side effects answers this.
The review found that there’s no difference between the two drugs in terms of serious side effects. There was no difference in the A way of expressing the chance of an event taking place, expressed as the number of events divided by the total number of observations or people. It can be stated as ‘the chance of falling were one in four’ (1/4 = 25%). This measure is good no matter the incidence of events i.e. common or infrequent. of death nor in whole body side effects, with the exception of gastrointestinal effects, which were more likely with bevacizumab. The authors conclude:
“Health policies for the utilisation of ranibizumab instead of bevacizumab as a routine A treatment, procedure or programme of health care that has the potential to change the course of events of a healthcare condition. Examples include a drug, surgery, exercise or counselling. for neovascular AMD for reasons of systemic Refers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. are not sustained by evidence.”
The review includes published and unpublished trials, none supported by the drug manufacturers. We know from a Cochrane review that sponsorship of trials by drug or device manufacturers leads to more favourable results and conclusions for the sponsors’ products than in non-industry sponsored trials. As for the companies behind ranibizumab and bevacizumab, they’ve been fined for colluding to exclude the cheap drug (more of that here in this Cochrane editorial). The review’s results will need to be verified when all the trials are fully published, but current evidence suggests that if a difference between the drugs exists, it is likely to be small.
Evidence you can trust?
Scarce resources for health need to be wisely spent. It’s essential to have the best available evidence on the The ability of an intervention (for example a drug, surgery, or exercise) to produce a desired effect, such as reduce symptoms. and Refers to serious adverse effects, such as those that threaten life, require or prolong hospitalization, result in permanent disability, or cause birth defects. of treatments, for the good of the individual of course but also to enable good management of our health budgets. Gordon Guyatt speaking at the Cochrane Colloquium in Hyderabad this week, reminded us that the first principle of evidence-based medicine is that decision-making requires systematic summaries of the best available evidence. This review is a great example of how this can look in practice, showing that there’s no justification for policies favouring the prescription of the more expensive drug. It should herald a change in practice, with a significant cost saving yet no compromise in patient care.
Why should you trust this evidence? Cochrane is an independent, non-profit, global network of health practitioners, researchers and patients, finding and synthesizing the best available evidence to help people make informed decisions about health. There’s a great deal of work going on within Cochrane to produce reviews addressing the questions that most need answering, to produce them more quickly whilst maintaining quality, and to improve the way the evidence is shared so that they are more useful, usable and used. So far, so good. But what if the best available evidence isn’t very good and what if there’s other evidence that we can’t get our hands on?
Cochrane reviews bring together results from clinical trials and these vary hugely in how good they are and how useful their findings. Each review contains a careful assessment of this and what future researchers need to consider. A brilliant series of papers on increasing value and reducing waste in research was published in The Lancet earlier this year and you can find those here. One of the biggest problems we face is that of buried evidence, Clinical trials are research studies involving people who use healthcare services. They often compare a new or different treatment with the best treatment currently available. This is to test whether the new or different treatment is safe, effective and any better than what is currently used. No matter how promising a new treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. that don’t make it to publication.
Getting all trials registered and reported
This story highlights the importance of independent, reliable evidence to guide people making decisions about treatments. We need the results of all clinical trials to make informed choices. Yet about half the clinical trials for treatments currently in use have never been published and trials with negative results are twice as likely to remain under wraps [Song et al, 2010]. Cochrane supports the AllTrials campaign, calling for all past and present clinical trials to be registered and their full methods and summary results reported. Will you? You can find out more about the scale of the problem, what can be done about it and how you can help, on the Alltrials website here.
Moja L, Lucenteforte E, Kwag KH, Bertele V, Campomori A, Chakravarthy U, D’Amico R, Dickersin K, Kodjikian L, Lindsley K, Loke Y, Maguire M, Martin DF, Mugelli A, Mühlbauer B, Püntmann I, Reeves B, Rogers C, Schmucker C, Subramanian ML, Virgili G. Systemic safety of bevacizumab versus ranibizumab for neovascular age-related macular degeneration. Cochrane Database of In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2014, Issue 9. Art. No.: CD011230. DOI: 10.1002/14651858.CD011230.pub2.
Formoso G, Marata AM, Magrini N, Bero L. A clearer view of evidence in treating macular degeneration: off-label policies and independent research [editorial]. Cochrane Database of In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2014;(9):ED000090
The Cochrane Library, Wiley Press Room [online]. 2014. Cheaper alternative to licensed drug for treating eye disease has similar side-effects says new Cochrane Reviews are systematic reviews. In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. [press release]. 14 September 2014. Available from: http://eu.wiley.com/WileyCDA/PressRelease/pressReleaseId-112142.html
Lundh A, Sismondo S, Lexchin J, Busuioc OA, Bero L. Industry sponsorship and research outcome. Cochrane Database of In systematic reviews we search for and summarize studies that answer a specific research question (e.g. is paracetamol effective and safe for treating back pain?). The studies are identified, assessed, and summarized by using a systematic and predefined approach. They inform recommendations for healthcare and research. 2012, Issue 12. Art. No.: MR000033. DOI: 10.1002/14651858.MR000033.pub2.
Song F, Parekh S, Hooper L, Loke YK, Ryder J, Sutton AJ, Hing C, Kwok CS, Pang C, Harvey I. Dissemination and publication of research findings: an updated review of related biases. Health Technology Assessment 2010 Feb; 14(8): iii, ix-xi,1-193. Available from:http://www.journalslibrary.nihr.ac.uk/__data/assets/pdf_file/0005/64751/FullReport-hta14080.pdf