Suffer the little
children
I am on another bloody working party! I thought I had done my penance for the year with my RARA (Radical Approaches to Random Allocation) stint. This time the project name is JUSTICE: Joint Unified Standards for Treating Infants and Children in Evaluations. (The ‘joint’ means that it will apply globally, so we are in for several months of arguing with our colleagues at Medicine Springs to produce suggestions which our colleagues in our subsidiary Yesisnever Nippon will immediately agree to but never implement.) I detect the lame brains of our marketing department in this. It turns out that there is no choice but for us to do something, so we have decided to spin this by presenting it as an initiative. ‘Pannostrum takes the lead in treating children.’ (Yes, we have had a change of name following our recent merger with Nostrum Medical and that is another tedious story I don’t want to go into.) Of course, we have done no such thing in the past, for the very sensible reason that it makes no commercial sense to do what does not make commercial sense, and where markets are small and the risk of litigation is high you do well to leave well alone. Of course that doesn’t cut the mustard with your critics and the very same people who accuse our vaccines division of poisoning all the infants in the world and sue us every time any child who has had one of our vaccines falls ill, chide us for not doing more to develop medicines for the young.
However, the PPEA, that is to say the Pangean Pharmaceutical Agency (yes, I know that the acronym is one letter too long but it used to be the Pangean Pharmaceutical Evaluation Agency and, for reasons best known to them, they have dropped a word but kept the letter) have issued a new guidance document. They are concerned that too many medicines are being used ‘off-label’ by paediatricians to treat children. From now on every development plan is going to have to include a Paediatric Evaluation Proposal (PEP) as part of it.
This one is turning out to be particularly obnoxious, not just illogical but emetic because you can’t attempt any critical discussion of this without being painted as an ogre. In the mildly amusing film, Miss Congeniality, ugly duckling police officer Sandra Bullock is turned into a swan in order to go undercover at a beauty contest. Achieving the physical transformation turns out to be easier than managing the mental one, and in particular she has to learn that every would-be contestant is required to say that the thing she hopes for most is, ‘world peace,’ when interviewed by the oleaginous MC. Or, for those of you that like more literary examples, ask yourself which of King Lear’s daughters loved him the best. Was it the ones that said so? Well these days at Pannostrum, and indeed throughout the pharmaceutical industry either side of the regulatory divide, you can’t possibly say that you think this PPEA legislation might be counter-productive without being portrayed as a cynical, evil bastard. In my case, of course, such a description would be 2/3 correct but this doesn’t prevent my nearly puking every time I think of the smug morons at PPEA mentally patting themselves on their backs for the blow they have struck for all the poor sick little children in the world.
Anyway, the local kick-off meeting was led by Di Muddle of Corporate Regulatory Affairs at Pannostrum Pharmaceuticals. (I had hoped that the merger would mean that this dimwit could have been booted out but no such luck.)
‘Well,’ said Di, ‘this is a great opportunity for Pannostrum,’ (there was just the slightest hesitation as she pronounced our new name) ‘to take a lead in setting standards for the industry.’
‘Well,’ I said, ‘I think that is a strange way to put it in view of the fact that a) this is being forced on us by the p-pea-brains at the PPEA and b) that it is completely illogical.’
‘
‘Well’, I said, ‘when it comes to off-label use, that certainly is a problem, a scourge of our society as anybody familiar with the evils of tobacco and alcohol will know. Why every supermarket has notices explaining that it is a crime to sell cigarettes and booze off-label and the success of these measures in controlling the problem is legendary.’
‘Oh come off it,
‘OK,’ I said, ‘but ask Dick here whether, Fullagro® is every used off-label.’ I was referring to Dr Richard Rising one of the key figures in developing Fullagro® and a member of our working party.
‘Well, yes,’ said Dick smiling, ‘we can’t exclude that some under eighteens have experimented with our product and of course many adults who are in no need of a prescription for Fullagro® have taken it, but that’s not what we are talking about here.’
‘Granted,’ I said, ‘and I assume that you will be applying for a paediatric waiver for your current successor project to Fullagro®, Getiton®.’
Di Muddle looked puzzled. ‘Why would we be seeking a waiver?’
‘It’s for male erectile dysfunction,’ I said, ‘or what used to be known as impotence and now is responsible for half the spam email in the world. However,’ I said, ‘maybe you are right. After all, I suspect that our contraceptive, Femchoice®, is prescribed by lots of GPs off-label to under sixteen year olds. Good luck to anyone designing a trial in contraceptives in future. We could enrol patients in the trial and inform the police at the same time.’
‘Oh come, on
‘OK. I said let’s talk seriously. We did a full and extensive evaluation in children when we developed Konsentrate®. Why was that?’
‘It’s for attention-deficit disorder, of course,’ said Viper in his usual grating tone, ‘the market is children and highly successful the drug has proved too.’
‘Well, thank goodness that important unmet need has been satisfied,’ I said. ‘However, we did not study Memrem® in children. Why was that?’
‘I think you need to take it,’ said Viper, ‘It’s for Alzheimer’s.’
‘Quite,’ I said, ‘so we are agreed that there are conditions where we would study children anyway because it makes commercial sense and there other where we wouldn’t because it makes no medical sense. So what can the legislation be designed to address?’
There was a pause, so I answered the question myself. ‘Clearly, it must be addressing cases where there is a medical need but no commercial interest.’
‘Talk about the bloody obvious,’ said Viper.
‘So what will happen to the profitability of such projects?’
‘That’s obvious, again. The profitability will go down.’
‘Quite and that means that for some indications we will not develop a treatment we would otherwise develop because the reduction in profitability will no longer make it attractive. What will happen then?’
‘Well, some adults who might otherwise have been treated won’t be,’ said Dick, who is quicker on the uptake than most of the medical advisors at Pannostrum.
‘Quite. So for some indications the net effect of the legislation will be no increase of effective study of medicines for children but a reduction in medicines for adults.’
‘Well OK,’ said Angina indignantly, ‘ I can see that might happen in some cases but what about the others where we would develop the drug anyway.’
‘Well now you are making a case for cross-subsidisation. You are saying that the profits for treatment T in disease D in adults should be used to subsidise the otherwise unprofitable study of treatment T in disease D in children. But suppose that in fact a bigger unmet need for children, slightly less unprofitable, but still unprofitable were indication I for which we could develop medicine M using the money spent on disease D in children. Wouldn’t that be a better use of the money?’
‘Well I suppose it might be,’ said Angina, ‘but you know as well as I do that the money wouldn’t be spent in that way and if the industry in general can afford to run more trials in children, legislation to make it do so makes sense.’
‘Perhaps,’ I said, ‘but there are two separate issues here. One is that the pharmaceutical industry may be making excess profits. If that is the case, then measures should be taken to reduce those profits generally.’ A sort of strangled choke of indignation escaped from Viper’s throat. ‘The other is whether for any fixed budget in health it makes sense to spend it on unprofitable initiatives. Imagine that you have a total fixed budget for trials in children. Any money you spend on one cause is not available for another. Wouldn’t you prioritise in terms of need, and if NOPE[1] is doing its job properly mustn’t the reimbursement be following the need?’
‘I’m with you on much of this,’ said Dick, ‘but I think that you are overlooking one point. The pharmaceutical industry generally makes money out of off-label use. Isn’t it hypocritical of us to sell but wash our hands of the consequences.’
‘That is an excellent point, Dick. I note by the by, however, the fact that the makers of homeopathic and natural remedies also make money by selling products to children when they haven’t done the trials, but in those cases there will be no requirements from the PPEA. I suppose the attitude there is it makes no sense to require proof in children when you don’t need it for adults. However, if the problem is doctors using medicines they shouldn’t, then why don’t they make it illegal? Why don’t they turn what are currently regulations in marketing to regulations in prescribing. Why don’t they forbid off-label use?’
Angina and Dick looked shocked.
‘Interfering with clinical freedom!!!’ said Angina.
Dick thought for a while. ‘You see
‘My point, exactly,’ I replied. ‘We can’t study everything. There are circumstances under which the information we have on one group of patients must guide our choice of treatment for another even if the information is imperfect. Attempting to interfere with this process may have counter-productive consequences. What I can assure you is that although the PPEA committee that drafted this documents will have produced rhetoric, sentiment, pontification and cant, the one thing it won’t have done is produces a decision-analytic model of the consequences of this legislation.’
Di Muddle had been looking increasingly perplexed by our deliberations. She cleared her throat. ‘This is all very interesting but I take it that we are all agreed that company policy will be to require PEPs for all projects in development and that we will be reviewing all existing products to see which ones require additional paediatric development. We can issue a corporate communiqué to that effect. Is there anything we need to add?’
‘Yes,’ I said, ‘you forgot to mention that we are all in favour of world peace.’
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[1] NOPE= National Office for Pharmaceutical Evaluation