January 28 2019.
Open letter to David Haslam, NICE
Our paths nearly crossed at an IAPT meeting in London in 2016 but you opted not to speak in a session that had me covering “Some Questions for NICE” – a lecture covering issues that have given rise to this letter.
We brushed by each other in May 2018 when Chris Van Tulleken, in The Doctor who gave up Drugs, based on input from me, is shown contacting NICE about antidepressants and children. NICE refused to comment but claimed they were revisiting this topic.
What concerned him (me) was that pretty well everything in the antidepressants and children domain is ghost written and that every single trial including the 2 trials, which had been the basis of approval of fluoxetine for children in the US and the UK, were negative trials.
File on Four covering the same issue had the same material and message from me. They were rivetted but then claimed they couldn’t fit the material into their programme, opting instead, like Dr van Tulleken, to feature Andrea Cipriani, despite being made aware that Dr Cipriani’s work is necessarily based on ghost written material and that he had had no access to any of the data behind the studies he worked on.
Faced with difficulties in moving some substantial concerns forward, I opted for publication in a peer reviewed journal – the article is attached.
I have given a TedX talk on this topic – https://www.youtube.com/watch?v=vpTqei5hZ3g
And presented the issues in the Welsh Assembly – https://youtu.be/oku_8t8MLek
Both talks cover material presented in several national and international fora – including how the NICE process fails us – to which I can now add the following for future talks.
On January 23rd, an email from NICE informed me that a draft guideline on depression in children and young people was up for consultation. I was not surprised to find physicians advised in the case of more serious disorders to consider a turn to fluoxetine, or combining fluoxetine and CBT, before turning to sertraline and citalopram if these treatments fail.
Then on the afternoon of the 24th, a follow-up email indicated that sections of the guideline were blocked off from comments. These sections included those I might have commented on. Hence this open letter to you, as you personally may be unaware of the issues.
The fluoxetine trials, which were used for paediatric approval in 2001, just like the paroxetine trials a year later, were negative on their primary outcomes. FDA recognised this for both fluoxetine and paroxetine and were willing to approve paroxetine and not mention in the label that the trials were negative, leaving an unchallenged ghost-written article in the public domain to claim paroxetine worked well and was safe. Essentially the same applies to fluoxetine.
Following the fluoxetine approval, a Panorama programme made it difficult to approve paroxetine, sertraline and other SSRIs.
I am not saying these drugs should never be used. There is evidence they may produce a benefit in paediatric OCD. I can envisage using them in conditions other than OCD. But these drugs cannot be used safely unless clinicians are aware of the true state of the evidence as regards both benefits and hazards, which include making young people suicidal, wiping out their ability to function sexually, perhaps forever, or hooking them to treatments forever.
The guidance mentions that in the case of fluoxetine the risk benefit ratio has proven favourable. This seems to mean provided there might be some benefit any risks can be taken. The data do not indicate that on balance the benefits outweigh risks. There are more negative trials for fluoxetine than any other SSRI. In the case of the only notionally independent trial (TADS), the study that underpins your recommendation to combine fluoxetine and CBT, there were 34 suicidal acts on fluoxetine against 3 on placebo. I appreciate that this isn’t stated clearly in any of the 7 TADS publications but it is readily ascertained – see Hogberg et al, attached.
The guidance mentions sertraline, perhaps because Dr Cipriani recommended this for adults – on the basis of ghost-written articles and a lack of access to the data. FDA assessments suggest sertraline may be the weakest of the SSRIs for adults.
Citalopram is also mentioned as an option. Again, the data are inaccessible, the articles ghost written, and one of the key trials has I believe the highest rate of suicidal events in paediatric SSRI trials. The company then marketing it, like GSK, ended up resolving a Department of Justice action against them for a substantial amount of money.
This situation echoes 2004/2005 when NICE personnel compiling the first guideline in this area, wrote an editorial in the Lancet, Depressing Research, questioning whether it was possible to produce guidelines when trial data is inaccessible and the published literature all ghost written.
I’m not clear what the Care in National Institute for Health and Care Excellence means. It may just refer to Care of the Elderly Services. I take Care to mean there is more to Health Care than just another Service Industry – something more like taking responsibility for others as when in the care of people with diabetes we used to tell patients they needed to prick the sides of their finger when taking a blood sample as they might need the pulp of their fingers should their eye sight fail later. As a family doctor, I expect you would agree that there is always going to be a need for those of us on the coalface of clinical care to be alert to the way those who seek our Care integrate technologies, such as a drug that might make you suicidal, into a life that has to be lived.
I have not added any honorifics to your name or mine. This letter is from one person to another, not one office to another.