I don’t mind referring to scientific research where relevant, but I’m not of the mind that only things that have been ‘scientifically proven’ have merit. One reason for this is that there’s plenty of things that we might do in practice that appear to consistently help people, but have not been subjected to systematic study. An example? How about water drinking. I (and many other practitioners) find that when individuals take steps to maintain their hydration throughout the day, they generally feel better in terms of their physical and mental energy. The benefits here do seem to be really consistent, with the vast majority of people sensing benefit. In the absence of appropriate science do we know whether the effect is down to water drinking or the placebo effect? No. Does it matter? No, again (not in my view).
The other reason for not believing that science is the be all and end all is that, well, not all science can be trusted implicitly. When vested interests are at play, studies can be designed (and interpreted) in a way that helps to guarantee a particular ‘result’ and conclusion. There has long been known to be a potential problem with this sort of thing. For example, in this blog post I wrote about a study that found that in studies of statins (cholesterol-reducing drugs), industry funded studies were 20 times more likely to report positive results for drug made by the study’s sponsor. Study conclusions were 34 times more likely to be positive too.
I was interested yesterday to read about a study just published in the Annals of Internal Medicine that reviewed the relationship between drug company funding and trial results [1]. Of 546 trials reviewed, 346 (63 per cent) were primarily funded by the pharmaceutical industry. 74 (14 per cent) were funded by the US Government, wile the remaining 126 (23 per cent) had other sources of funding (non-governmental, non-profit organisations).
Of these trials, just two thirds were published. Of these published trials, more than 85 per cent of industry funded research reported positive results. That compared very favourably with the 50 per cent of government-funded studies reporting positive results.
The percentage of positive trials reported from trials funded by non-profit and non-governmental organisations, 72 per cent were positive. However, some of these studies had at least partial funding from the industry. In these studies, positive outcomes were reported in 85 per cent of the studies, compared to 61 per cent in studies with no industry funding.
Another interesting finding of this study was that 2 years after the completion of the studies, 56 per cent of non-governmental, non-profit organisation sponsored (with no industry funding) studies had been published. With studies primarily funded by the industry, this percentage was 32 per cent.
Now, one potential explanation for the discrepancy in these publication figures is what is known as ‘publication bias’ basically, the practice of publishing some results but not others. There’s potential here for drug companies to published results that support the effectiveness and use of their products, but not publish or delay publication of studies that are unlikely to help their bottom lines. An example of this was the so-called ‘ENHANCE’ study, which found that two cholesterol-reducing drugs caused more blockage in arteries than one. Two years after the completion of this study, the results had still not been published, and in fact needed to be forced out of the sponsors by decree of a US Congressional enquiry. You can read more about the ENHANCE study debacle here.
The burying of negative trial results used to be quite easy, on the basis that many studies could be happily conducted in near-secrecy. This are different now, because there’s more pressure placed on drug companies and investigators to register trials before or early on in their conduct. Once registered, things look a bit fishy if the results of the study do not emerge in a timely manner. If the ENHANCE study had not been registered, there’s every change hardly anyone would have known anything about it.
The ENHANCE study is not the only evidence we have that new trial regulations might be helping combat publication bias.
A commentary published earlier this year [2]draws our attention to the fact that while initial statin trials were overwhelmingly positive, more recent evidence has been generally negative. Specifically, since 2005, all but one statin trial has yielded neutral or negative results [3-11].It was in 2005 that new regulations regarding the registration and publishing of clinical trials came into being.
The one positive statin study since 2005 is the so-called JUPITER trial [12]. However, this study has been the subject of considerable controversy, and scrutiny of its findings reveal numerous implausible results which have caused some to question the role of the study’s sponsors in the analysis and presentation of the data [13].
The problem with publication bias, obviously, is that it can give us a very skewed view of reality. Some people may want that, of course. However, I personally find it very gratifying that some souls are doing their best to expose the practice and make it increasingly more difficult for drug companies and others with vested interests to engage in it.
References:
1. Bourgeois FT, et al. Outcome reporting among drug trials registered in CliniclTrials.gov/ Ann Intern Med 2010;153(3):158-66.
2. de Logeril M, et al. Recent cholesterol-reducing drug trials: new data, new questions. J Lipid Nutri 2010;19(1):65-92
3. Kjekshus J, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med 2007;357(22):2248-2261
4. Barter PJ, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med 2007;357(21):2109-2122
5. Tavazzi L, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. Lancet 2008;372(9645):1231-1239
6. Rossebø AB, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med 2008;359(13):1343-1356
7. Fellström BC, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360(14):1395-1407
8. Wanner C, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353(3):238-248
9. Knopp RH, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non Insulin-Dependent Diabetes Mellitus (ASPEN). Diabetes Care 2006;29(7):1478-1485
10. Cowell SJ, et al. A randomized trial of intensive lipid-lowering therapy in calcific aortic stenosis. N Engl J Med 2005;352(23):2389-2397
11. Kastelein JJ, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Engl J Med 2008;358(14):1431-1443
12. Ridker PM, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359(21):2195-2207
13. de Lorgeril M, et al. Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal. Arch Intern Med 2010;170(12):1032-6
