Conflicts of interest, financial or otherwise, clearly influence some people's actions some of the time. When most experts in an area of medicine share a similar conflict, it can be hard to know if you are getting an unbiased opinion, guideline or recommendation. Disclosure of conflicts is a good idea, but once disclosed you are still left wondering how an expert's opinion might have been shaped and altered by the conflict.
Conflicts, though, can be something on which to blame all manner of disliked opinions, errors in judgment, or just plain mistakes, out of all proportion to their actual role in a given circumstance.
Recently in BMJ, Jeanne Lenzer published a piece titled "Why we can't trust clinical guidelines". Ms. Lenzer, a journalist, has written about conflicts of interest frequently, and she and Shannon Brownlee published a list of industry-independent experts that journalists could contact for unconflicted opinions about new research and products. For my own disclosure, I am on this list and think it's a great idea, though journalists have only very rarely contacted me through this listing.
In her current piece, though, I think other problems are being mistaken for conflicts of interest, at least if we are talking the financial kind. Ms. Lenzer writes about guidelines recommending that steroids be given to patients with spinal cord injuries. (She uses this as a backdrop to a more current concern about recommendations around alteplase for stroke, but I'm not going to address the alteplase issue in this post). She makes it clear that she feels this is an example where conflicts of interest have led to actively harmful guidelines:
One expert estimated that more patients had been killed by the treatment in the past decade than died in the 9/11 World Trade Center attacks.
She sets this up by pointing out that the lead author on a study published in the NEJM supporting the use of steroids in spinal cord injury, "...declared he was an occasional consultant to steroid manufacturers Pharmacia and Upjohn...." He then went on to be the "sole reviewer" on a Cochrane Collaboration review of the issue.
So, in this view of the world, an author has occasionally consulted to Pharmacia and Upjohn; those companies make steroids, and so the opinion about whether to administer steroids to patients with spinal cord injuries is so tainted that more people are killed by this harmful therapy in a decade than died in the WTC attacks on 9/11.
Is this really believable? Could large pharmaceutical manufacturers and their occasional consultants actually care enough about an inexpensive, uncommon therapy to desire to promote it in the face of harm?
I've been following the overall issue of steroids in spinal cord injury because it's an intersection between evidence and values that causes real problems for anyone who wants to write a guideline. There are published trials suggesting neurologic benefit when steroids are administered early after spinal cord trauma. However, to find these benefits, the data must be interpreted with a forgiving eye. An early subgroup must be split off from the trial as a whole, and the definition of early does not seem to have been made a priori. As such, the benefit may just be a statistical blip -- in general, post hoc subgroup analyses should be viewed with suspicion. Additionally, the actual neurologic benefit seen, even in the "early" subgroups, were quite small and perhaps of marginal clinical importance.
Weighing against the use of steroids are their obvious harms, including an increased risk of infection in trauma patients who are already setups for developing such infections.
The problem, though, is that many people are willing to accept a significant increased risk of death for a small chance of benefit when the issue is spinal cord injury. I watched a group of physicians trained in medical evidence who had participated in a detailed review of the data around steroids for spinal cord injury vote overwhelmingly that they would want steroids if they suffered such trauma. (They were far more willing to take the steroids themselves than recommend it for their patients based on the data, but that should always give us pause about where real-world values and preferences lie.)
So, are the issues with guidelines around steroids for spinal cord injury really do to conflicts of interest?
I do think the author of the NEJM trial is conflicted, but not because he has some association with some large companies that happen to make steroids as one of their products. Instead, he has the universal intellectual conflict of having studied something, wanting to find an important result in his research, and wanting what he found to be true. I would not view him as the best person to judge whether the subgroup analyses in the trial were reasonable, or whether the neurologic benefits in the trial were clinically meaningful.
But the big problem with guidelines around steroids has relatively little to do with these author conflicts. Instead, the problem for guideline developers is that we are very uncertain that steroids help but have some evidence that they might. Though being administered steroids likely increases the chance of dying, this is apparently a chance that many people (including a roomful of fully-informed physicians) appears ready to take when the alternative is so grim (at least to those who are not currently quadriplegic; it's worth pointing out that another problem with values and preferences around this issue is that people living as quadriplegics typically view their quality of life as much better than the quality of life that healthy people anticipate for themselves were they to become quadriplegic.)
So to come back to where I started, conflicts of interest can be a huge problem for the development of trustworthy guidelines. But there are many other things that can be problems, and for a particular guideline these may loom much larger than conflicts. It's important to diagnose the problem correctly in each case, so that we don't view every flawed (or potentially flawed) guideline as due to a single cause.