The Sensible Diet

The EMEA’s Committee for Medicinal Products for Human Use (CHMP) have pulled the marketing authorisation for rimonabant (Acomplia) [PDF]. This isn’t much of a surprise. What is interesting in this case is the reasoning, which not only addresses safety concerns, but also concerns about effectiveness in clinical practice (as opposed to clinical trials). Effectiveness, rather than efficacy, is going to become a much more important aspect of judging the benefit and harms of drugs in future.

Following the assessment of the available information on the benefits and risks of Acomplia including data from studies completed since it was granted marketing authorisation, the CHMP confirmed at its 20-23 October meeting, that there is an approximate doubling of the risk of psychiatric disorders in obese or overweight patients taking Acomplia compared to those taking placebo.

The CHMP considered that the new data from post-marketing experience and ongoing clinical trials indicated that serious psychiatric disorders may be more common than in the clinical trials used in the initial assessment of the medicine. The CHMP was also of the opinion that these psychiatric side effects could not be adequately addressed by further risk minimisation measures.

In addition, the CHMP noted, that the effectiveness of Acomplia in clinical practice is more limited than was expected on the basis of the clinical trials, because available data indicate that patients generally take Acomplia only for a short period.

Also interesting is the reaction to the withdrawal from certain quarters. I suspect there isn’t much surprise in the drug safety arena, but a pressure group has expressed some reservations about the withdrawal.

Dr Colin Waine, chairman of the National Obesity Forum, said: “My patients were doing very well on it, and they will now have to stop and come off it.”

“Patient safety must be foremost, but I always thought that if you ruled out the patients with depression, you ruled out the problem with the drug.”

In the past, patient pressure has occasionally led to withdrawn drugs being re-launched, because patients argued they were willing to accept the risks for the benefits they felt they obtained from the drug. The National Obesity Forum does not appear to be a patient group, in that it seems to consist of professionals interested in obesity, rather than obese people desiring treatment for obesity. No-one doubts that obesity is a problem. However, shock horror, who do we find sponsoring the National Obesity Forum? Yes, the manufacturers of rimonabant, Sanofi-Aventis.

Website funded by educational grants from
Abbott Laboratories
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MeatandHealth.com

The National Obesity describe themselves as an independent charity. Independent is a word that I would have thought is fairly widely understood.

independent
adjective
1 free from outside control; not depending on another’s authority
2 not depending on another for livelihood or subsistence
3 not connected with another or with each other; separate

Michael Rawlins was right.

You may wish to check your pantry.
The Food Standards Agency has today issued a food alert about novelty food products from China, including chocolate-flavoured ‘willy spread’, containing melamine.

Melamine is an industrial chemical that should not be present in food. Milk products containing melamine have been at the centre of a major food incident in China.

An Agency spokesperson said: ‘This is a first. We’ve never had to put out an alert before on “willy spread” – chocolate-flavoured or otherwise. But on a serious note, if anybody has used any of the affected products they shouldn’t worry, the risk from the melamine in these products is low and it is very unlikely to be harmful.’

Remember, if you are concerned about past exposure, Paracelsus’s words, “The dose makes the poison”. Via Ben Goldacre.

How bizarre.

Someone has decided to complain to the GMC about a group of doctors involved in the decision-making process over MMR vaccine. The complainant is Bill Walsh, the author of a particularly dumb letter about the Hornig study. Sadly he is also the President of the Autism Treatment Trust, which just shows you how some of the autism community, for want of a better term, have been lead down a disastrous dead end by Wakefield and associated pseudoscientists, journalists, and, latterly, celebs.

Mr Walsh of Glasgow, Scotland, said: “I am concerned about what I believe is the absence of proper tests since 1998 when Andrew Wakefield first raised concerns about the MMR jab.

“The complaint is as rigorous as possible so it makes it so much more difficult for them to try to close it down.

“There cannot be one rule for Andrew Wakefield and another for those in powerful positions.”

The full list includes Professor Sir David Hull, Professor Michael Langman and Professor Andrew Hall of the Joint Committee on Vaccination and Immunisation. Also reported to the GMC are Professor Sir Alisdair Breckenridge, Professor Gordon Duff and Professor Colin Blakemore, all of the Medicines and Healthcare Products Regulatory Agency and Sir William Stewart, chairman of the Health Protection Agency.

The complaint said they ignored Dr Wakefield’s work, which claimed certain groups of children are damaged by the MMR jab, because of fears it would undermine the immunisation programme.

It also alleged the programme had been undermined by bad judgments and by the use of scientific studies of the general population to support the safety of the MMR jab, instead of studies of vulnerable groups as identified by Dr Wakefield.

Given only cranks are willing to promote the idea of a link between MMR vaccine and autism after all the studies (epidemological and virology) and the documented scientific failings in the initial Wakefield studies, this complaint will not get far. If it did, we would presumably witness a parade of cranks at the GMC in support of the MMR vaccine-autism link who would wilt under the weight of that most important form of evidence: facts.

However, the result is probably not what matters. Mr Welsh will be able to point to any perceived or real inaction by the GMC as an example of a powerful medical conspiracy to suppress the truth. That is the only argument left to the anti-MMR vaccine lobby. The science is lost, only the conspiracy remains.

Even at the start of this debacle, Wakefield’s work did not provide evidence which supported his claims that MMR vaccine was linked to autism. If you accepted his claims, his advice to split the vaccine was illogical. What evidence did he have that the measles vaccine was only a danger in combination with other vaccines?

What the individuals Mr Welsh is complaining about are guilty of, is balancing the risks being proposed by someone shouting his mouth off at a press conference, without any supporting evidence, against the benefits of vaccination on reducing childhood diseases. At other times the same people he is complaining have drawn attention to other legitimate safety concerns about vaccines (such as the risk of idiopathic thrombocytopenic purpura with MMR vaccine). If cui bono is the mantra, then why was this adverse effect of a vaccine accepted as legitimate?

Mr Walsh provides a valuable reminder that these people were correct in their assessment. Wakefield was not a heretic in the mold of Galileo Galilei. He was wrong. Well done to them all for not caving in to lobby group and media pressure over the past ten years, and sticking to the science. If Mr Walsh has employed the same rigour to his complaint that he applied to his recent letter on the Hornig study, we are unlikely to hear much more of this story.

I recently attended the 8th International Society of Pharmacovigilance Conference in Buenos Aires, Argentina. Vaccine safety has been a growing component of this conference, it was addressed in Bournemouth last year, and this year had several sessions on how to improve the detection of real adverse events caused by vaccines, and how to address the public health problem of false safety concerns. Communication with the media and the public are key to this, and a local story explained by Dr Miguel Tregnaghi in a session on pharmacovigilance in biologicals and advanced therapies was a prime example of how poor media reporting can be round the world, before the truth has its boots on.

Tregnaghi is a physician interested in infectious disease in Latin America. I’m not sure when the programme organisers arranged for him to present “Clinical trials: patient’s safety and AE’s accurate media communication“, but he certainly had a tale to tell. After outlining the changes in ethics relating to clinical trials, and their importance in improving the ethics and quality of clinical research, he started to tell the story of a vaccine safety scare he had recently been involved in. His comments came through a live translation into English into Spanish, which lost some of the passion he obviously felt.

Tregnaghi is currently involved in a trial of a paediatric pneumococcal vaccine. Since August he had been caught up in a story in the media that alleged that 14 children had died in a clinical trial of a vaccine. News stories in Argentina included “A lethal vaccine? It is being investigated if 12 babies died due to an experiment”, and “6,000 babies participating in a controversial experiment.” The news was even reported in in Spain, “A vaccine under study could have killed 14 babies”.

The trial is called COMPAS, and news of the controversy has been widely reported on the internet, with Ed Silverman’s Pharmalot site covering the story. It’s also been reported approvingly by the UK’s most active anti-vaccine site, JABS, and by Bob Fiddamen’s blog. Tregnaghi cited 900 news sources carrying the story. The story ticks a few boxes: clinical trial outsourced to foreign country, fears of vaccines, and an evil corporation looking to make some bucks. However, the story doesn’t stand much scrutiny.

COMPAS is a phase three study looking at efficacy of the vaccine in Latin America against pneumococcal otitis and pneumonia - which are common childhood diseases in Latin America (Argentina, Columbia, and Panama). It is not outsourcing of a trial to a less regulated market. It is a trial of vaccine within the population it is planned to be used within. Mortality rates of children in the population at large are about 18 per thousand, the trial population mortality was seven fold less. Examination of deaths in the trial failed even to show a temporal relationship with the vaccine, and the Argentine and Columbian regulatory authorities were in favour of the trial continuing, and had no concerns over safety, and expressed the ongoing need for the vaccine in the paediatric population.

Tregnaghi listed a few adverse consequences of the irresponsible reporting; fear in the community, withdrawals from the study, discrediting of the vaccine, and potential problems in obtaining funds to run future trials - for the benefit of the population. He outlined the challenge of giving science legitimacy to the public, and fostering democratic control by citizens on the direction of scientific research, when a hostile media were willing to uncritically carry scare stories.

He outlined two possible solutions/strategies:

1. Cope with the media: Researchers should be trained in the task of dissemination of information in a complex media-influenced society.

2. Journalists should be more considered, and there was a need for more journalists interested in science who can approach researchers with fair criticism.

I think point one will make little difference, unless it is in combination with point 2.

Kevin Leitch has an interesting post which documents Andrew Wakefield’s mistakes, although that’s probably too kind a word to use, over the years. Here is the conclusion, but you should read the whole thing.

A review of the career of Andrew Wakefield is a trawl through the underbelly of science. Wakefield did not do experiments to seek the truth – he did experiments to confirm his own beliefs. He produced junk science for over a decade and did immense damage to patients with Crohn’s disease, and autistic children and their parents. Hopefully the GMC will nail the charlatan, and show some sympathy for the Royal Free clinicians who thought Wakefield was honest. The Andy Wakefield show has now moved to the USA where he can get the attention he craves and he can play the role of the selfless seeker of truth whom the establishment had to silence. Being a victim is a good career move for him. It will help Thoughtful House sell junk therapies for autism to desperate parents and allow Andy to live in a really big house, where he can entertain his showbiz friends. He really wanted to be a famous scientist, but he was rubbish at that, so he had to become (in)famous by other means.

The Truth About Andrew Wakefield