SHIT stands for Secret Health Ingredient in Treatment – see SHIT Happens. In the early twentieth century SHIT was some supposedly secret magic chemical. In the early twenty-first century SHIT is important information about adverse effects of a drug that has been kept hidden.
In SHIT Happens, we reported that RxISK has adverse event data on a range of GSK, Pfizer, Lilly and Merck drugs, drawn from patients and doctors within the USA and elsewhere.
Generic pharmaceutical companies have been in contact to find out more about these adverse effects in order to meet their regulatory reporting requirements. Branding companies like Pfizer and GSK have not.
A colleague in response sent this piece by John La Mattina from Pfizer in Pharma & Healthcare, Sept 3rd 2013. The tone – we are poor misunderstood good guys – seems part of the through and through branding that goes with branded drugs. This is fed through to the sales representatives in the field and the cleaners in the building so that everyone is singing from the same hymnsheet when in fact what is involved is an operation that comes closer to a final nail in the coffin of someone who has an adverse event than even the faintest concession by a branded company that their drug might be causing problems.
For more on this Branded tone, see the forthcoming GSK’s Journey to Transparency.
“At the end of my first year of running research at Pfizer PFE +1.72%, I drafted a year-end letter to send to all my colleagues thanking them for their hard work and dedication, and wishing them a happy and restful holiday season. As a matter of protocol, I ran the letter by the head of HR, who told me that I needed to change it. The reason was that, at the end of the letter, I said that everyone should turn off their computers, take a break from email, and relax with their families and loved ones. My HR head reminded me that some employees had to work over the holidays, specifically those whose job it was to monitor the reporting of any adverse events that might be reported for our drugs. While 99% of the R&D folks were on holiday, a small cadre of colleagues would be working over the holiday break. I changed the letter accordingly, both acknowledging and thanking those who played this important role.I share this story because most people don’t have a clue as to the vigorous requirements put on pharma by the FDA for reporting a drug’s side effects. In fact, when I write about the pharmaceutical industry, particularly posts that support the value that the industry adds to healthcare, I will often get attacked that I am defending an evil empire. Many believe that the industry hides negative data on its drugs. The following is typical: “Side effects should be monitored and updated and told to patients and doctors. Not hidden as they are right now.Actually, specific regulations exist as to how the industry must handle and report adverse events. To make sure that I had my facts right, I checked with a former colleague of mine in a pharma legal department who shared the following information. Pharma’s reporting requirements are defined in the U.S. FDA Code of Federal Regulations (21 CFR 314.80). Essentially, a U.S. Drug Manufacturer (Marketing Authorization Holder) is required to report serious, unexpected, drug related individual case safety reports within 15 calendar days of initial receipt as well as to report any follow-up information within 15 calendar days of receipt of new information.
How does a company hear of an adverse event? There are two ways. First, within the U.S., physicians and other healthcare professionals can utilize the FDA’s MedWatch Adverse Event Reporting System to report an adverse event seen with a marketed product. In addition, physicians can contact the manufacturer of the marketed drug directly by using telephone contact numbers (toll free) and/or websites provided by the company as mandated by the FDA. Should a physician only report the adverse event to the FDA’s MedWatch program, that information is then forwarded to the drug manufacturer.
“This system is not perfect as the MedWatch Program is voluntary. Thus, a physician could be derelict in reporting an adverse event. There are currently no repercussions should a physician choose not to inform the drug manufacturer of an adverse event seen with its product. However, there may be State, County or Institutional regulations (e.g., hospital standard operating procedures) that obligate healthcare professionals to report these events.
“Every pharma company has a group in its regulatory division dedicated to tracking adverse events and duly reporting these side effects both internally as well as to the FDA. This work goes on every day of the year and is taken very seriously. Contrary to the views of some of my critics, side effects are, in fact, monitored – very diligently”.
For those of you concerned about the poor folk working Xmas Day and Thanksgiving in GSK and Pfizer, it is perhaps worth clipping out a section from the Access to RxISK Data post that ran last November to make it clear just how seriously Pharma tell themselves they take their duties. (See also SHIT Happens and Won’t get fooled again).
If Andrew Witty, John La Mattina or Neal Parker were to take a train tomorrow and I was sitting in the seat behind and was overheard mentioning a side effect I was having on one of GSK’s drugs part of company mythology is that they are legally bound to report this to the regulator.
Here is Leigh Thompson then the Chief Scientific Officer of Eli Lilly being deposed by Paul Smith on this issue in 1994 for the Fentress trial in Louisville Kentucky after Joseph Wesbecker on Prozac shot dead 8 of his co-workers and injured 12 more before killing himself.
Q. The other day you said something that I have a question about. You said something about…. employees calling adverse event reports in?
A. The rules under the DEN system that I put in place … was that any Lilly employee anywhere in the world that learns of any adverse event through any source, and I’ve done it from cocktail parties and overhearing conversations, should in fact report to DEN within twenty-four or seventy-two hours, depending on where they are in the world. So, yes, we got a lot of adverse events, including ones I report because I’ve literally called up DEN and said, you know, that I overheard a conversation in the hallway just now that somebody’s wife was taking Ceclor and had an allergic reaction.
Q. Do you usually stop and ask for more information about that adverse event or do you just report what you overheard in a conversation in the hallway?
A. Depending on who the individual is, but, for example, you remember you showed me the document about that meeting of the expert opinion leaders that I had gone to wherever it was, I had another Lilly employee come to that meeting and follow me around so that that person could in fact report all the adverse events that I was hearing, so that I wouldn’t have to do it myself.
I think it fulfills a regulatory requirement.. if you right now told me that you had heard of a patient who had taken one of our drugs and who had their hair turn blue, I will guarantee you that I would call DEN up within two days and that would be in the DEN database. And I may or may not ask you for more information, but I would identify you.
Q. So let me make sure I understand. You feel it is your absolute duty to report a conversation that you have overheard in the hallway, but you don’t necessarily feel it’s your duty to report an issue raised by another regulatory agency and the analyses that were done by the drug company in response to that issue being raised?
A. Under the FDA laws and regulations, I think you’ve stated it correctly.
Against this background it seemed appropriate to alert Andrew Witty last March to the fact that we expected RxISK to start generating data on GSK’s and other drugs – mentioning that despite everything many still considered GSK to be among the more responsible pharmaceutical companies. GSK’s response was to misattribute the remark that they were a responsible company to me and to thank me for this recognition, but to turn down a possible collaboration while in a follow up letter stating their full commitment to their regulatory obligations. [There’s the Branding again].
We still haven’t heard from GSK or Pfizer despite accumulating large amounts of adverse event data in people taking sertraline and paroxtine and other company drugs – See SHIT Happens.
There are endless ways to adhere to the letter of a regulation but not its spirit. This is why you hire lawyers.
The campaign for access to clinical trial data is about getting a proper picture of the effects of a drug. Company efforts to restrict access to trial data is in fact more about restricting access to information about the hazards than about the relative inefficacy of treatment. GSK’s proposals to have an analytic plan and to underpin access and a Safe Haven – Safe for GSK – in which no-one will be able to snoop around and find adverse events they weren’t meant to find – are all about restricting access to adverse event data.
Clinical trials are not the correct way to establish the hazards of a drug – the diseases in which they are conducted commonly mask the hazards of treatment (The Spin that no Data can Overcome, Cri de Coeur, Once is Never, The Unbearable Lightness of Being.)
The best approach to hazards is to do what RxISK is trying to do. That is harness the real world experience of people taking a medication to get best quality descriptions of events as well as applying standard approaches to causality such as checking for dose response, challenge-dechallenge-rechallenge and other related methods. The best way to determine risk-benefit ratios is to ask doctors and patients what they think of the possible trade-offs between the effects of a drug – as RxISK asks but clinical trials don’t. We get both doctors and patients to look at the wider impact of an event in a person’s life in addition to reporting on just the event.
In contrast the pharmacovigilance put in place by the branded pharmaceutical industry out seems aimed at frustrating reporting or in the event there are reports it seems aimed at ensuring that we get the most degraded possible descriptions of events with no accompanying details (See American Woman, American Woman 2).
This is an industry that has succeeded in building a culture in which even good descriptions of the effects of drugs are dismissed as anecdotes – except of course for patients reporting stunning benefits on treatment.
An industry where Ian Hudson, then of GSK, now head of Britain’s FDA (MHRA), can get hundreds of reports of a problem like violence on Paxil-Seroxat and still say he has seen no evidence that Paxil-Seroxat causes any problems (See Burn in Hell).
This is an industry that somehow regularly fails to send reports of adverse events to FDA as per regulations – as Neal Parker’s AbbVie appears to have done (See Sharing the Yellow Stuff).
Rarely in the field of human communication has the reality of what happens on the ground been so at odds with what the powers that be proclaim.
This is probably not the way Andrew and John and Neal see it. But they must know that branding is all about pimping things up to look good but – to continue the metaphor – above all making sure the glossy image doesn’t fart.