Black Triangle

In times gone by regulatory bodies concerned with drugs were a black box. Decisions were made and conveyed to the public, with little explanation. Other concerns, that were preliminary and yet to be confirmed by further evidence might be delayed. Public engagement with regulators was minimal. For a number of years things have been changing.

The FDA have recently issued their first ever list of items with suspected safety issues identified by their Adverse Event Reporting System (AERS):

The information is being provided under provisions of the Food and Drug Administration Amendments Act, signed into law Sept. 27, 2007. The law requires that FDA inform the public each quarter of new safety information or potential signals of serious risk, based on the agency’s review of adverse event reports contained in AERS.

The appearance of a drug on this list does not mean that FDA has concluded that the drug has the listed risk, or that FDA has identified a causal relationship between the drug and the listed risk. It is on the list only because FDA has identified a potential safety issue.

“My message to patients is this: Don’t stop taking your medicine. If your doctor has prescribed a drug that appears on this list, you should continue taking it unless your doctor advises you differently,” said Janet Woodcock, M.D., director of FDA’s Center for Drug Evaluation and Research.

The reports to AERS are spontaneous reports from patients and medical staff of suspected adverse events associated with a drug. These reports are essentially hypothesis generating, although they can sometimes led to direct action depending on the nature, and severity, of the reports. The list of drugs involved is here, a fact sheet here, and further explanation is here. There is a danger that the media, or public, could take simplistic messages from the FDA list, but on the other hand openness about such signals may make the media less prone to the “sudden-crisis” story. Most adverse drug reaction issues evolve over a series of months or years as evidence is collected. Some become confirmed. Many are not. Perhaps we will obtain more sober reporting?

Another change is the way that patient groups can engage with regulators. There are dangers in this approach. If the patient group is little more than a quack pressure group, utterly unwilling to have an intelligent informed discussion about real issues then little may be gained. In other cases, engagement may bring real benefits to regulators and patients.

In the UK there have been concerns about withdrawal reactions from SSRI anti-depressants. Andrew Herxheimer discusses this from one perspective at the Canadian Medical Journal. Herxheimer studied patient reports of withdrawal reaction and suicidality associated with paroxetine. The Yellow Card reports referred to in the next paragraph are spontaneous reports of suspected harms submitted to the UK regulator, the same as those submitted to the FDA’s AERS.

Patient reports of ADRs are commonly dismissed as anecdotal or unscientific. However, the collective weight of the patient accounts of experiences with paroxetine therapy was profound. Reports from users and relatives — especially with respect to behavioural effects — communicated information that professional reporters can never be expected to provide. They were far richer, and described suicidality and withdrawal symptoms much more clearly and intelligibly than the Yellow Card reports. The analysis of over a decade’s worth of Yellow Card reports suggests that miscoding and flawed analyses by regulators led to an underestimation of the risk of suicidal behaviour during paroxetine therapy. In some cases, depending on the word the reporter had used in submitting a Yellow Card, different terms were used to classify indistinguishable phenomena (e.g., “withdrawal,” “discontinuation” and “dependence”).

The UK now accepts patient reports at http://www.yellowcard.org.uk.

An example of regulator engagement with a patient group is the report of a meeting with a blogger on the MHRA’s front page. The MHRA met with Bob Fiddaman, who writes the Seroxat Sufferers blog, to discuss withdrawal issues associated with SSRI antidepressants. The report of their meeting is here. It seems to have been an interesting meeting. In the following extract RF is Bob Fiddaman is RF, and SM and KW are senior MHRA staff.

KW asked RF what he thought of the Seroxat PIL’s Section 5, “Stopping Seroxat”. Early in the section it says “When stopping Seroxat your doctor will help you to reduce the does slowly …”. RF felt that this was over-optimistic. He also felt that the advice about dosage reductions of 10mg a week (which SM noted was based on clinical trials) was too large an increment in view of his own experience – he needed to reduce by 1mg a week, only practicable with the liquid – and the experiences of others. And he felt that the signposting to the liquid form, “It may be easier for you to take Seroxat liquid during the time that you are coming off the medicine” was inadequate. SM agreed that steering patients towards the liquid could be made more obvious; and it could be helpful if such a steer was also given to doctors, in some document such as the NICE guidance.

The regulator are obviously listening. Bob thinks so. I have some sympathy, as this blog has on a number of occasions noted Seroxat’s story and the appalling behaviour of GSK. I have less time for Bob Fiddaman’s buying into the supposed HPV vaccine scam, although I suppose his experiences make him more susceptable to such conspiracies theories. He also links to the well known crank anti-vaccine site whale.to on the issue of the “MMR/Autism debacle” as he terms it. Whale.to is a conspiracy website which propagates anti-semitic material, such as the full text of The Protocols of Zion and other material like this:

The present government of Israel was set up by the High Masonic Rothschild-controlled Jews, and Rothschild has had an alliance with the Jesuit General since 1876, with Adam Weishaupt. This is the very same Rothschild powers who betrayed the Jews into the hands of the Nazis, killing many Jews all throughout Europe, betraying their own Jewish people. These are the very same powers who run the nation of Israel today.

No one should take anything seriously on the whale.to site, and those who cite it approvingly fall foul of Scopie’s law. It is therefore disappointing, although perhaps understandable to some degree, when individuals who may have legitimate concerns undermine their credibility by buying into all supposed “failings” of the pharmaceutical industry and regulators – regardless of the evidence.

When this blog started 5 years ago, I noted in a brief post about Seroxat the growing influence of user groups. The MHRA have also been paying more attention to the role of the internet and blogs. This summer a Market Research report was produced for the MHRA which looked at blogs and consumer groups. You can download it here [PDF]. It’s an interesting read, and this blog, and many others you might know of, turns up in a diagram of “Top Influencers” (if only).

The executive summary states:

The most influential of the mainstream media – BBC, BMJ, New York Times, and Guardian – rely not on blogs at all but on the official sources of information, government departments, regulators, pharmaceutical companies etc. Bloggers gain their influence from dense links amongst themselves and associated groups like AHRP, and from occasional links from the mainstream media – The Times links to Fiddaman blog, for example.

There are two agendas in the conversation: the official studies into the drug and its efficacy and drawbacks; the second is the experience of patients who have taken the drug and its impact on them, amplified through campaigning sites and bloggers. The two agendas converge only rarely. What this means is that the two groups are to some extent talking amongst themselves.

This is undoubtedly true. To address this the report also advises that the MHRA uses language that the patient group might use, and that information “is available in flat HTML pages and on blog-style urls, for
example mhra.gov.uk/news/is-seroxat-safe”. The MHRA meeting with Bob Fiddaman is a step forward on the first point, although language can be constrained by science and evidence, but the fact the meeting is only available in PDF format on the MHRA website at an the url:

http://www.mhra.gov.uk/Yourviews/Consultations/Medicinesconsultations/Othermedicinesconsultations/Discussionswithstakeholders/CON025699

is a sign perhaps that some improvements can still be made.