The idea that we should actively and scientifically compare treatments that are in widespread use, but currently with haphazard variations based on poor or no evidence, is a vital part of improving medicine.
In my own field, the care of the critically ill newborn, there are huge variations in some outcomes. Survival differences between centers are much larger than the survival differences ever demonstrated in simple clinical trials. We must find out which of the variations in practice lead to better outcomes.
Without the trials that compare such treatments there will be limited improvements in medical care.
Comparative effectiveness research therefore needs to be promoted and supported.
I knocked off a blog post recently about the proposed OHRP guidelines for consent for such trials. Which, although a specifically USA initiative, will affect all of us in time. I focused on how difficult they are to understand or operationalize. But a deeper appreciation of the potential impacts has been published in the PNEJM. The commentary by John Lantos effectively destroys the reasoning of the OHRP. It is brief and worth reading in full.
One particularly pertinent phrase is the following which refers to potential research subjects (or parents):
They should not be misinformed into thinking that their doctor’s preferred treatment is always and necessarily the safest and most efficacious and thus that any alteration from that treatment adds risk
This is in fact the crux of many of the criticisms of SUPPORT, that being in the trial prevented doctors from exercising their best judgement, and therefore increased risk, because doctors somehow know best (even in the absence of data). It is the crux of the criticism of the ARMA trial by Dr Natanson (who spoke at the OHRP meeting about SUPPORT) and the criticisms of many (non-physician) ethicists also.
John Lantos puts a bit of reality back in the discussion, Doctors only know best if they have good data to tell them what is best. Being in a randomized trial is no more, and much data suggest less, risky than not being in a trial. If you have a similar chance of receiving a treatment outside of a trial as within the trial, then how can you state that the trial is causing an increase in risk?
The editors of the NEJM (I will drop the prestigious bit I think, as it is getting tedious) are equally scathing :
We disagree with the proposed guidance because it suggests that within the standard of care there is a known differential between treatments. But it is precisely because no net differential is known that the research is being conducted. The fundamental nature of research equipoise means that doctors are uncertain as to whether there is benefit or risk that is predictably associated with one treatment or another. The goal of the research is to determine whether such a net differential exists. To report a differential risk or benefit in the informed-consent documents of standard-of-care research suggests that there are known differences between one standard treatment and the other.
To suggest that there are foreseeable risks in such a study is misleading. A potential trial participant will suffer the false impression that there is a known net difference in risks and that they can avoid risk by not enrolling in the study. Neither impression is true.
Now I do think that research subjects (or parents) should know why we are doing the research, which is going to be because we don’t know of a net difference in outcomes between the treatment arms, and, for future patients to get the best care, we need to know if there is a difference. Which means that, at the end of the study, we might well find out that one mode of treatment is preferable (or sometimes, that we understand better the balance of risks and benefits so that we can better inform future patients). But we need to tell them clearly about these issues, so that they can make an informed decision about whether to participate, without implying that doing so increases their overall risks.
I hope the OHRP are listening to these criticisms, I think they probably are listening, but how much they are willing to be change them is more questionable.