UK Minister Wants All Antidepressant Trial Data
23 CommentsBy Ed Silverman // March 3rd, 2008 // 12:52 pm
Drugmakers are going to be ’shamed’ into handing over their clinical-trial data on the effects of antidepressants, amid growing concern that the pills may not work as well as originally promised, The Guardian reports.
A government minister has taken the unprecedented step of calling on pharma to give the data to the body that will review the current depression guidelines, the National Institute for Health and Clinical Excellence, or NICE. Ivan Lewis, the minister with responsibility for mental health, says that ‘a failure to do so would leave the inevitable impression they had something to hide,’ the paper writes.
You may recall that NICE, which looks at the effectiveness of all treatments and recommends to the UK’s National Health Service how meds should be used, is embarking on a new look at the SSRI antidepressants. Its most recent guidance was published four years ago. However, NICE has no legal right to see unpublished data and can only request it from a company, which might refuse to give it if the findings were negative, the Guardian writes.
Backed by the government, NICE is now set publicly to ask for all the data, which would leave pharma facing huge criticism if they don’t hand it over. The toughening stance follows the publication last week of a study that found antidepressants don’t appear to work well - unless they were being given to the most severely depressed patients. The study showed that when patients on the drugs were compared with those who were taking a placebo they showed similar rates of improvement.
The number of prescriptions for antidepressants hit a record high of more than 31 million in England in 2006, with more than four million people thought to be on them, the Guardian writes, adding that, even though official guidance stresses they should not be a first-line treatment for mild depression, they are still being routinely prescribed.
“I have no doubt that medication can and does help some people with mental health problems. Equally a major expansion of psychological therapies that Alan Johnson (the Health Secretary) announced last week reinforces the need for an end to the “prescription not therapy” culture which has characterised our mental health system,” Lewis tells the paper. “I would call on any company in possession of any relevant evidence to make it available to Nice. The failure to do so would leave the inevitable impression that they have something to hide.’”
Tim Kendall, head of the National Collaborating Centre for Mental Health, says it has been impossible to get access to unpublished trials in the past. “We know that there have been thousands of trials since the drugs were licensed. We would like to use the data and recrunch it using our own methods and do a proper analysis,” he tells the Guardian.
In 2005, the Labour manifesto included a promise to make it mandatory for companies to hand over published data, but under EU law Britain is unable to force foreign companies to do so.
Jack2
I read the paper alluded to in this article, and it is interesting. But what isn’t always clear from short blog posts is that the paper concludes that anti-depressants cause a statistically significant greater improvement than placebo for patients (Drug treatment resulted in a 1.80 point greater improvement on the Hamilton Rating Scale of Depression), even when unpublished trials are included in the analysis. The authors main point is that NICE, which defines a clinically significant difference as 3 (a reasonable but somewhat arbitrary definition). At this standard, drugs only work in patients with severe depression (a HRSD score of >28).
In the defense of the FDA (who I don’t work for), since the study makes them look unfairly ludicrous for approving these drugs, I also wonder if all the studies included in the author’s analysis used clinically meaningful doses of drug. For example, the company may have been running a study to specifically determine the minimum effective dose. This dose didn’t work, and was ultimately not approved, but it could have been included in this meta-analysis. But it doesn’t seem very relevant to me that an anti-depressant doesn’t work when used outside of the recommended dosage range. Other possibilites include using the drug in a patient population that the drug was ultimately not approved for (example: patients with mild depression). Does it matter if the drug doesn’t work in patients ultimately not intended to receive the drug?
Ed Silverman
Hi Jack2,
Yes, the study, which can be found by clicking the link that takes you to my previous post on this topic, noted the pills only work for the most severe patients, and so that’s how I reported it. I’m afraid, however, that I can’t answer your question about dosing, and it’s a good question.
It should also be noted that the paper was written by psychologists, who stand to gain from any shift in funding and emphasis from pills to therapy, which in fact is now afoot in the UK. I posted about that last week, too.
Regards
ed
Jack2
Good point Ed. Although it’s a slippery slope for someone like myself to discount a study written by a certain interest group just because they belong to a certain interest group - since I work for pharma. I’ll trust what they do say as factually correct, but scrutinize the methods suspiciously - a good policy for anyone reading any paper*.
The authors also point out how they needed to contact the FDA to get the studies not available in the published literature or on the companies website, to basically demand the studies through the freedom of information act. You can usually just call the company and get them to send you the information.
As someone firmly anchored in the drug-world (pharmacist, PhD pharmacology, works for a drug company) I’ve got my own opinions on therapists. I think it depends on the diagnosis that sends you to a therapist. Some mental illness responds well to therapy, some requires drugs and therapy, and for some I think therapy does very little and drugs are your only hope - but that’s just my opinion.
*Even academic researchers with only government funding have biases (I’ve argued here that govt. supported academic researchers have more financial gain at stake than industry researches, but that’s really off-topic
Matthew Holford
Jack2 wrote:
“…Does it matter if the drug doesn’t work in patients ultimately not intended to receive the drug…”
Well, yes, because it seems that the vast majority of depressives (apparently self-diagnosed and “professionally” diagnosed), are prescribed drugs. The UK mental health charity puts the figure at 83%. I’ve also read (sorry, can’t reference it, just one of those snippets that stuck), that the vast majority of prescriptions for depression are written for those with mild depression, for which, as you note (and thanks to The Verve), “the drugs don’t work”.
So, the upshot is, that there’s a whole bunch of people, who could go for a run, or seek psychotherapy, and experience the same level of relief from their symptoms. That’s NICE’s position (ie, its recommendation to doctors), incidentally, although it may also be Kirsch’s. Neither of the non-drug options carry the side effects associated with SSRIs, of course.
Matt
Matthew Holford
Sorry, that should read “the UK mental health charity, MIND…”
Matt
Lisa Van S
Jack2,
You can just usuallly call the company and get them to send you the information!!..
How funny is that!!…I have a bridge I can sell you. If you are that gullable,.. I can anticipate getting very rich!!!
someone
Actually, the really important point for the UK is the side effects. Not only must they pay/cover/provide the drug to the patients but they are also on the hook for any ancillary medication to offset the side effects. Then there is the long term over all health effect. This study provides a great argument for putting preventative measures in place, something we are seriously lacking in.
I read that new information about Ritalin indicates that there seems to be an increase in heart problems for patients and former patients when they reach 30 years of age. This could have devastating consequences as this is a significant portion of the population who are just starting to enjoy some financial independence and find their place in the economy. With the way Ritalin was so over prescribed (in my opinion anyway)the cost to the healthcare system could be quite a challenge.
So, yeah, side effects are an important issue.
The other issue is that one would hope it would provide an opportunity for prescribing physicians to provide more genuine care and not be so quick to pick up a pen and write a script. Of course, they may get less knocks on their door to attend dinners and trips from the sales reps (armed with the prescribing information they buy from IMS…)which technically would free them up more to be more well, doctors (a novel idea to some out there) and counsel their patients on what they need to do.
So, let’s take a tally of some of the benefits that can and must be derived as a result of this report: less prescription cost in the systems, less trips and other forms of grafts for doctors and patients who are actually healthier - hmm how appealing.
truthman
“Does it matter if the drug doesn’t work in patients ultimately not intended to receive the drug?”
Well unfortunately these drugs have been prescribed at a ridiculously dangerous level not just for mild depression, but also for shyness, agrophobia, anxiety , ocd, hot flashes, irritable bowel, insomnia, grief and everything else in between…
When you begin to prescribe a drug which has a just marginal posituve use in the treatment of severe depression to every tom , dick and harry who is merely going through normal life crisis then you will get problems..
GSK marketed Paxil as a”lifestyle” drug..
Their DTC ad campaigns were seductive and suggestive ..
The wanted eveyone to take paxil and they cashed in on common human fears, neuroses and insecurites..
A triumph of marketing over science..
In 10 to 15 years time, people will look back on the SSRI era as the biggest con job in medicine…
Unfortunately in the mean time, there are hundreds of thousands of very vulnerable people trapped on these drugs..
The pharmaceutical industry should hang its head in shame, its behaviour throughout the whole SSRI debacle has been utterly disgraceful..
pg
Its not like the drug makers and their funded ’scientists, stand to gain, or have gained enormously, from THEIR studies of course. Of Course Not!
pg
But why not concentrate on how something WITHOUT sometimes fatal, and often disabling, side effects just MIGHT benefit people concerned about scientific integrity and ethics, huh?
pg
Don’t worry about science, Jack - just stick to your job.
Donna
Hi ED,
Would just like to say I spent a Lovely afternoon in Trenton today, learned alot..as I do also on my trip’s to DC…and as I’ve stated before profound change’s are taking place..thank’s to you and all the squeeky wheel’s….keep up the good work…
Nathan
pg says: “Its not like the drug makers and their funded ’scientists, stand to gain, or have gained enormously, from THEIR studies of course. Of Course Not!”
You can be sarcastic all you want pg, but the reality is that the scientists actually don’t gain anything from thier drugs. Sure, the executives make a nice profit and the shareholders make a nice profit. But those of us back in the labs doing the research don’t profit much at all from drugs that reach the market. If one of my drugs makes it to the market and sells $2 billion a year, guess how much of that will make its way to my pocket? NOTHING. I’ll get my normal paycheck. I might possibly get a promotion. I might get a few thousand $ extra in my yearly bonus. And I’ll likely get a few pats on the back from management. But that’s about it. There is very little incentive for dishonesty in preclinical and early clinical drug discovery. Late stage clinical might be a different story, but that’s out of my realm of study.
Matthew Holford
Donna wrote:
“…and as I’ve stated before profound change’s are taking place…”
Alert… alert… alert… sarcasm follows:
I don’t suppose these profound changes would include the de-criminalization of off-lable marketing, together with the introduction of pre-emption nationally, would they?
Matt
“Be alert: the world needs more lerts.”
Lisa Van S
Nathan,
I agree,.. well stated.
Jack2
You can call the company. 20% of my job is distributing unpublished studies to HCPs who call to ask for them (I never worked on an SSRIs, or for a company that makes any anti-depressants). These authors didn’t call, so we don’t know. And the level of detail they would have gotten (probably less than 500 words covering the main point), may or may not have been sufficient for a meta-analysis but it would provide a decent summary of the trial.
The other issue ignored here is cost. Even if therapy worked as well as the drugs, therapy was more expensive than the drugs when the drugs were still on patent. Now that the drugs are generic it’s a landslide cost victory for the drugs.
I know that people here have a lot of strong feelings about SSRIs. But the papers abstract makes the FDA look ridiculous. 80% of people here may enjoy seeing the FDA look ridiculous; the fact is that this group of authors, with all of its biases, with all of its digging around, still had to admit that antidepressants caused a statistically significant improvement in depression. Furthermore, their methods may include a lot of irrelevant trials. If you want to ignore the numbers and just go on your gut reasoning you can, I choose to look at the numbers.
Former pharma Marketing Exec
Jack2:
But the real problem is that this study says that the major portion of the patients were not helped any better than with a placebo. It does say that for those who were seriously depressed there was an effect. When the right drug gets to the right patient - well that is what we should all strive for. It’s the unnecessary over medicating of people going through mild depressions which by the way, tend to clear up by themselves within 12 weeks without treatment. For this patients population (which I would imagine is the largest portion)derive no benefit and suffer serious side effects and then become dependent. That is the real problem.
Matthew Holford
Jack2 wrote:
“…The other issue ignored here is cost. Even if therapy worked as well as the drugs, therapy was more expensive than the drugs when the drugs were still on patent. Now that the drugs are generic it’s a landslide cost victory for the drugs…”
Doesn’t that depend upon how long a patient is prescribed the drugs (and also the difficulty that a patient might have coming off them)?
Counselling is about changing behaviour, such that a patient not only deals with the current issue, but also avoids recurrences. A drug can’t do that.
Matt
Matthew Holford
Former pharma Marketing Exec wrote:
“…When the right drug gets to the right patient - well that is what we should all strive for…”
But that’s the point, isn’t it? There is precious little provision of psychotherapy (at least in the UK, on the NHS), for those with mild/moderate depression. If one can’t afford it privately, one doesn’t get it. As such, doctors prescribe drugs for conditions for which they are no more effective than therapy.
The Worshipful Company may say “hey, we just make the things, we’re not responsible for inappropriate prescribing”. And the quacks may say “hey, we just treat people with the resources available, if there’re no counsellors, we prescribe drugs”. And the regulators may say “yes, sir”. Could one of you halfwits actually take responsibility, instead of pretending that the issue isn’t yours, because, between you, you’ve created a mega-sized cluster fuck, and the patients are paying the tab, just now.
Matt
pg
“Lisa Van S
Nathan,
I agree,.. well stated”
Well Lisa, thats nice. People like us are trying to protect children, like YOUR children, and you agree with NATHAN? Wow. No wonder you allowed YOUR CHILD to be put on drugs.
pg
We are fighting to protect children. Mostly AMERICAN children because their parents seem unable to understand and put them on drugs then complain when they have adverse drug reactions. Why do we bother? Who knows? But we will continue to protect european kids from drug companies and parents who have allowed it to happen in the US.
pg
You shouldn’t have been listening to the Jacks and Nathans of this world. You should have been listening to YOUR CHILD. If you had, she would never have been given drugs, she would have been given what you, as parents, were meant to have given her. Parental love, support and guidance. Isn’t that so?
Nathan
pg,
I’m left assuming that you disagree with my statement? What part do you disagree with?