Neal Parker Avoiding Adverse Events

Editorial Note: Neal Parker, Section Head Legal, Biologics Strategic Development at AbbVie, was an industry representative on a panel organized by EFPIA – The European Federation of Pharmaceutical Industries and Associates on August 27th in Bruxelles. In two posts AbbVie’s Mission to Discover New Diseases and AbbVie’s Mission to Discover New Patients, we gave a transcript of his talk with some commentary – further comments would be welcome. We will make a version without what may be irritating interruptions available to download when the transcript is complete next week. We will also with your help make a translation available.

While this was happening colleagues have been translated the RxISK access to data petition into French, Spanish, Han, Hindi, Urdu, Turkish, Swedish, Serbian, German, Portuguese and other languages. This brought it home to us how difficult translation can be. Even if the original seems very clear, it can be very difficult to capture the essence of what someone said – or meant. Things get Lost in Translation. With apologies to Mr Parker then, the translation is here and his original words can be downloaded from here.

Neal Parker

An American in Bruxelles doesn’t sound quite the same as an American in Paris when there is a Trade War on this is the place to be. I think you can take it that European and American companies are on the same page here. This has little to do directly with the health of the nation, except in so far as Adolf Jahn, then CEO of Roche, put it 40 years ago, when asked if the company should be accountable publicly for the vast profits they made from Valium the Humira of the day:

“I would say No. My task is to develop Hoffman la Roche –  why are we doing it – we are doing it because it is absolutely clear that the only chance for social security is to make economies by finding new drugs”

Companies have a number of different rights when it comes to developing new drugs. We have patent rights, in return for which we are supposed to disclose the content of our innovation in order to stimulate further development by other companies or individuals – but hey not to China or Korea. We have also data exclusivity rights which further protect our interests after any data have been made public.

What every woman wants?

What we also want is Commercial Confidentiality Rights – Privacy rights. There is a big fuss at the moment all over the twittersphere about Lea-Ann Ellison who has been lifting weights when 8 months pregnant. When some people criticized this, she and other women naturally responded that what goes on in a woman’s body is her business – no one else has the right to tell her what to do. The same holds true for religious beliefs – you don’t want to be told by the Government what to believe (except if they tell you to take Vaccines).

We in AbbVie want just what every woman like Lee Ann wants. Based on the data we have in house, we want the right to make up our own Mind what it means for Us, and we don’t want middle-aged men like Tom Jefferson or Peter Gøtzsche telling us our business or worse again regulators like Guido Rasi. The fact that other women might want to know what they are putting into their bodies – well that’s their problem not ours.

Perfidious AbbVion or Albion?

One thing I would like to clear up is this. At the moment industry is portrayed as split with companies like GSK in favor of transparency and other companies less so. Nothing could be further from the truth. GSK and ourselves are on the same page here. They have just been more successful at co-opting the AllTrials campaign and the UK House of Commons and portraying themselves as being in favor of transparency than we have.

I have to hand it to GSK that their Trojan Horse gives the appearance of transparency and irreproachability but will lock up our secrets in a much better way than anything any other company has come up so far. Perhaps this is one for the free market manuals – GSK have paid more fines and have come up with better final solutions.

Let’s talk about adverse events

You all know that in the course of clinical trials adverse events happen. We have a range of different ways to handle these which involve simply not recording some adverse events or coding them in a way that will hide their identity. Thus famously suicidal ideation was coded as emotional lability. We can code an event as non-response or we can distribute events across a range of codes.

We can use statistical techniques – as Ian Hudson the new Head of MHRA – famously did in the Tobin case – saying that if something is not statistically significant it hasn’t happened. Or we can band the data so that we look at what happens to the average person in the trial rather than to certain individuals who may have had a bad outcome. Astra-Zeneca and Lilly have been able to do this well with problems like weight gain on their drug so that despite the evidence of patients ballooning up in weight, they were able to trot out graphs to say the science showed there was no problem.

Some events are so tricky that its just easier not to put them into the Clinical Study Report (CSR). Where’s the problem showing this to a Tom Jefferson or Peter Goztsche you might think – well unlike regulators, some of these guys might begin to wonder about a dog not barking and in that case we’d have a problem. We don’t want to be up for Canicide.

Let’s talk about adverse events

What you need to remember is that a CSR is not designed to offer our full and frank appraisal of what our drug does or what a trial has shown. It’s an effort by a company, mainly the marketing department, to manage the data a trial throws up – so as to avoid an Adverse Event for the company.

Now our position on access to the data, skilfully deploying scares about patient confidentially to get some people onside, is that we have to have the appearances of transparency and that’s what we are offering you. If you’ve any sense you will accept the deal.

At the end of the day this means that you have to trust us to some extent. But we’re not going to make mistakes that put the company at risk. And if the company isn’t at risk then in the long run, broadly speaking, give or take some deaths here and there, it will be the better for you.

It will also be the better for the economies of the West in general and so we have widespread support for what we’re doing, just as the Arms industry has.

Nobel prize nominee?

GSK’s initiative is truly elegant. They suggest that everyone wishing to look at the data needs to have a structured analytic proposal approved. Once this step is agreed – and the amour propre of most scientists will get them to sign up to this – then we can afford to put an entirely independent panel of scientists in place to vet any analytic proposals confident in the fact that nothing can go wrong.

The terms of reference of this independent panel will make it impossible for them to accept a proposal from someone who wants to scrutinize the data to make sure we have it coded properly or someone who just wants to fish around in the data and see what it shows.

GSK have another clever control in place after the independent panel gives the researcher access to the data. I shouldn’t be telling you this but here’s how it’s done. Giving someone access to old style paper records even from just our healthy volunteer studies where there are no confidentiality issues involved meant that someone who perhaps might have gone in to look at the records to see if the drug caused people to become suicidal might notice a much bigger problem in passing – for instance that healthy volunteers after only two or three weeks on treatment had real problems on stopping. They even became depressed and suicidal.

Someone with this kind of access can cause us all kinds of problems – it becomes almost impossible for us to know how to fire-fight the many things that could start happening if we approved this kind of access.

But now that we’ve got these records in electronic form, if people are following a clear analytic plan we can ensure that they simply get to see only those bits of the data that are relevant to their analytic plan. In other words if you don’t know there’s a problem there and can’t put up a good case for how it might be investigated then you aren’t going to find out there’s a problem there. And of course you couldn’t know there’s a problem if you haven’t been able to fish around. [For more see Won’t get Fooled Again, Fishing in Harlow]

This is genius. It combines complete hands-off transparency with excellent research governance and not a chance of Adverse Events happening. Tick box paradise. Sir Andrew should really be offered a Nobel Prize for his contributions to health care. Well after all if the contribution is to the health of companies, the rest of you will gain too.

Aginus Kalinus

As a regulator I must say I am shocked by what you’re saying.

Neal Parker

Well you might be. We’ve been able to get by with letting the records go to you in paper form where people could fish and find out all kinds of problems that might have caused us terrible difficulties but we’ve been confident up to this that when shown to the regulator that you guys will be so sleepy behind your desk after a good lunch that no-one’s going to spot anything.

More so lately as you have been encouraged to partner with industry and told that regulation is all about enhancing company profitability and national competitiveness.

Jim Murray

If I’m going to challenge you how do I go about doing it?

Neal Parker

You don’t. If you lived in the United States you might have some chance as a plaintiff who has been injured by drugs or as a citizen able to take a petition out. We tried our hardest while George Bush was in power to close all these loopholes and to make it impossible even in the United States to challenge us but we didn’t quite pull this off.

Here in Europe you have no hope at all. We have most European governments exactly where we want them. There has never been a successful case against a pharmaceutical company in Europe that I’m aware of and the UK House of Commons has now written our favored proposal on data access into their recommendations on clinical trials. We even have independent groups like AllTrials in our close embrace. So you’re welcome to try taking an action but…

Jim Murray

Can my doctor share information about adverse events with other doctors?

Neal Parker

Let me put it like this. We wouldn’t want a doctor sharing the information with a journalist. That sounds like what you’d expect me to say but in fact, we would want them to share it with a journalist. Because when journalists get these things out there, even if it’s a story about an adverse event on a drug we are well able to use such stories to increase sales of our drugs. In stories about Humira all that people will hear from the article is that it’s transformed the lives of many people for the better and that it’s going to be the best selling drug of all time. So even if death is mentioned, it is not going to bother the average consumer if there’s the faintest glimmer of hope that the treatment might work.

We are scared as hell however of doctors potentially getting together with other doctors in a kind of resistance movement as it were. There’s no problem with patients on the street hearing about adverse events because they aren’t the real consumers. The real consumers are doctors and if they decide that it isn’t a good idea well we have a problem.

But we expect to have this problem solved soon. Doctors have been fairly toothless regarding adverse events up till this and we are fairly confident that with Nurse Prescribers and other non-medical prescribers in the future being cheaper for health care we will have a situation which is fully in our control (See Model Doctors and Professional Suicide).

To be continued.