I did something the other day that has bothered me for the past 72 hours: I decided not to publish a comment in my blog because of fear of retribution or possibly retaliation.
Today, I decided to correct that decision and discuss my concerns.
Although it may not be a momentous piece of information, it nonetheless made me think long and hard about why I made the decision I did at that time, and what the implications were for providing information to the public about current controversies in oncology.
The topic of my blog this past Saturday was about the changing face of oncology, as reflected in the annual American Society of Clinical Oncology meeting.
What has concerned me were the comments in my draft about an investigational cancer vaccine called Provenge.
As I noted in that blog draft, we live in a different world today than we did years ago when it comes to public knowledge and influence on the drug approval process.
We have more information readily available, with many more people having access to that information. I call this phenomenon the “democratization of information.”
Along with that democratization (if there is such a word) comes the sense among many that they want information provided to them so that they can make up their own minds regarding the validity, value and implications of that information.
It is one thing to have that information about, for example, a presidential candidate or a new car. It is something else, in my personal opinion, when it comes to a new medicine or a new treatment.
I agree with my colleagues that it is important that people have access to the information, but the subtleties of interpretation do require knowledge, training and expertise that are not possessed by most people who have not had training in medicine.
This brings us to the Provenge story.
I will admit that I am not privy to all of the information and primary data related to Provenge, an investigational vaccine being studied in the treatment of men with advanced prostate cancer. Much of what I do know comes from other sources that have reported on this topic.
That said, in a nutshell the story is that several years ago the company that has been working on this vaccine reported that their clinical trial intended to demonstrate that Provenge was useful in the treatment of advanced prostate cancer did not meet its goal.
Subsequently, on reanalysis, they concluded that there was some information in that “failed” trial which suggested that the vaccine may have in fact increased the lifespan of the men who received the vaccine.
The company then supplied the data to the Food and Drug Administration for review and possible approval of the vaccine.
Within the past several weeks there have been several news reports about the developments surrounding the FDA’s analysis and decision.
First, one of the FDA’s outside advisory committees suggested the vaccine be approved, despite some problems with the quality of the statistics that are normally used to determine whether or not in fact a drug (or vaccine, in this case) is effective for the disease in question.
A report in a widely followed cancer newsletter called The Cancer Letter reported that the advisory committee meeting was apparently raucous, with the advocates present in the audience making their opinions known very vocally when someone agreed or disagreed with their position that the vaccine should be approved for general use in the treatment of prostate cancer.
Subsequently, as again reported in the Cancer Letter, some highly respected cancer specialists wrote the FDA regarding their concerns about possible approval of the vaccine. They felt that the data did not support effectiveness, and pointed out that there were ongoing clinical trials that would directly answer these questions, without the statistical problems of the current data.
The FDA decided to not approve the vaccine, and await the results of the ongoing clinical trial.
That apparently led the advocates in favor of vaccine approval to develop a series of actions with the goal of changing the FDA’s mindset.
The advocates had posted an announcement on a website that they were planning a rally for Saturday morning at ASCO. They also planned a rally in Washington yesterday and today to meet with Congress and the FDA.
Their position is that someone who wanted access to Provenge should be able to receive the vaccine. The argument they make is that if it appears the vaccine may be effective, then why should men who are facing a fatal disease be denied the opportunity to receive the vaccine when it may improve their survival?
This is the question that piqued my interest in this topic, and how our standards may be changing when it comes to the decisions we make in caring for our patients.
For years, much of what we did as doctors—in treating ALL types of illnesses—was based as much on tradition and expert opinion as it was on science. Now, as physicians, we are trying to move our care into more of an evidence based model, where we develop the science to back up our actions.
But with the spread of the internet—and the democratization of information—we find patients and others are beginning to influence our treatment choices, much as is the case with DCA and now with Provenge. (Other alternative therapies are also driven by this “word-of-mouth” (or perhaps “word-of-internet” would be a more apt description) phenomenon, and are now very much a part of the landscape of cancer treatment.)
So that is what interested me. I also had expressed in the blog draft my personal opinion that based on what I had read, waiting for the results of the clinical trial was the appropriate thing to do.
We have seen too many examples in cancer medicine and other areas of medical treatment and practice where the initial thoughts have proven wrong—and even harmful—to ignore good science in this particular situation. (The current discussions surrounding the potential harms of erythropoietin come to mind as an example.)
On my way to the ASCO meeting, I heard that the situation may have become even more serious than I had realized.
What made me pull my comments from that draft blog was a message I received that serious personal threats had been made against two physician scientists who had urged the FDA to delay approval of Provenge, pending the results of the clinical trial. And, I was told, these were threats of the most serious type.
Because of the risk, I decided not to say anything publicly. Although I had written my blog on this topic, I edited the comments regarding Provenge out of the final posting which you may have read on Saturday.
For your background, what you see on my blog is generally what I write. I may make some editorial edits, or perhaps tighten up some comments. But I have never removed a “theme” from one of my blogs under pressure—either real or perceived--since I started writing it almost two years ago.
But this time was different.
As I spoke with some reporters who attended ASCO, a common theme emerged.
They, too, had become reluctant to cover the story because of fear of retaliation. One reporter said that in their opinion you had to “steel yourself” if you intended to report an opinion or comment in support of the FDA’s conclusion.
Frankly, this troubles me a great deal.
On Saturday afternoon I decided to give an interview to a major business journal and basically say that this is not the way we should do our science.
What I said was that we may not always agree on the science, but intimidation is not the answer to making evidence-based decisions regarding drug approvals. (As I write this, I don’t know if those comments have been published.)
Then, yesterday, the New York Times went public with confirmation that threats of physical harm had in fact been made against the experts who opposed approval of Provenge. The Times reported that one of the physicians actually had bodyguards with him as he presented at ASCO.
In that interview, the physician indicated his concern that more of his colleagues had not come out publicly to support him in his time of need. I suspect that, like me, many of his colleagues have been intimidated, and are frankly afraid to make a public comment.
As it turned out, the rally on Saturday had a small number of participants and nothing untoward occurred.
There were no meetings invaded, no sessions disrupted, and no one harmed.
As I said above, my personal opinion based on the information I have read is that it is appropriate to await the results of the current clinical trial to determine whether or not in fact Provenge improves survival in advanced prostate cancer before approving the vaccine for general distribution.
The question of access to investigational drugs is an important one, and one that is currently being debated in multiple forums. When it comes to drug (or vaccine) approval, we must have the best evidence possible that the drug is effective, and a valid understanding of what risks may be associated with the drug.
But to threaten established, knowledgeable investigators who honestly express their well-reasoned opinions, which in turn “chills” rational discussion is, from my point of view, simply unacceptable.
We will always be subject to those who try to influence our comments, decisions and recommendations. I personally try to limit those outside influences, and try my best to declare when I perceive there may be a conflict of interest that people should know about when I make a statement in a public forum.
Public debate and discussion is appropriate. Intimidation is not. Disclosure is essential.
Ultimately, I am hopeful that our decisions whether or not a particular drug should be approved will be based on the best evidence available, and the best quality interpretation of that evidence.
Yes, there are problems with the system currently in place. Every human system is subject to personal interpretation and potential error.
That does not mean that those involved in making those decisions and making comments on those decisions are not trying to do the best they can under the circumstances.
Fear and intimidation should not make us hold back the expression of our legitimate scientific concerns.
I know that the perception of potential intimidation influenced me a couple of days ago, and I hope that sharing these thoughts with you will help assuage the nagging guilt that has bothered me since I made that decision.
In the meantime, I hope that those who disagree with my position will be rational—and, non-threatening.