Stephen J Evans, Professor of Pharmacoepidemiology, on the recent licensing of a homeopathy preparation in this weeks BMJ:

It is tragic that we now have a respected body, the Medicines and Healthcare products Regulatory Agency (MHRA), granting a licence for a product for which there is not only no evidence of efficacy but good evidence against any efficacy. I have some sympathy with the MHRA in the face of a European Directive which has to be obeyed but which is almost totally irrational. However, I think that because “efficacy” appears in the directive and there is evidence against efficacy, it could have resisted granting a licence.

This fiasco takes us back to the days before drug regulation was introduced, partly to prevent the hazards of snake oil-type remedies. While this product may have no benefit, it probably has no direct harm either. But it may have major indirect harms—not only in individual patients who may not benefit from other effective remedies but also in a general sense by undermining the rational basis for medicine

On which note, adverts for snake oil here.

Right wing attacks on Obama’s healthcare reform are an echo of previous attacks in the UK during Bevan’s creation of the NHS.

For UK citizens it is hard to imagine a time when the NHS was perceived as a threat. Today the NHS is a sacred object in British politics, and those who wish to be critical of a government (of whatever political shade) merely need to say that they are defending the NHS to obtain public approval. Healthcare practitioners, when feeling threatened, will use the NHS as a shield to protect their interests. So attempts to use private providers to provide NHS healthcare to patients in the UK are presented as attacks or a creeping privatisation of the NHS. This love of the NHS did not always exist.

Back in January 1946 met the British Medical Association, told them his plans, and pledged them to secrecy. The British Medical Journal suggested doctors had been “gagged” and that doctors had been received by Bevan as a Victorian capitalist might deal with a deputation of workers.

There was a gradual ratcheting up of the rhetoric over the next few weeks. Dr Alfred Cox, a respected BMA member, noted that after examining the bill that “it looks uncommonly like the first step, and a big one, towards National Socialism as practised in Germany. The medical service there was early put under the dictatorship of a medical “fuhrer”. This bill will establish the Minister of Health in that capacity.” This was an extraordinary statement, given that the country had only recently finished fighting a war for survival against National Socialism. Right wing newspapers were equally concerned about the bill. The Evening Standard stated “the Bill is the first step towards the full-time employment doctors as State servants.” The BMA became became a battering ram employed by the Tory press and opposition politicians, who had been quick to spot the political opportunities to get Bevan.

By the end of April 1946 Bevan had eloquently talked the bill through a second reading in the House of Commons, winning the argument and the vote by 359 votes to 172. However, the BMA representatives were meeting at the same time. The BMA delegates opposed state ownership of hospitals by 210 votes to 29, control over where GPs practice by 214 to 2, and change to a basic salary and capitation fees by 209 votes to 9. Bevan’s NHS bill was described as “a clearing of the ground for the erection of that glittering ediface of a Socialist dream - a whole-time State salaried service.” A Dr Cockshut suggested doctors would become “West Indian Slaves”, and that the bill could be written in two lines: “I hereby take powers to do what I like about the medical service of the country - (signed) Nye Bevan, Fuhrer.”

Despite further worsening of relations between Bevan and the BMA, and threats of a boycott of the scheme, in the end it started on the 5th of July 1948, with 90 percent of general practitioners joining the scheme, and over 39 million patients signed up - with widespread support within the middle and working class. Opposition parties quietly forgot about their opposition, and the UK’s NHS has survived despite changes in government.

In the US, Obama is attempting to introduce much milder forms of health care reform than Bevan. He is concerned about controlling costs within the US health care sector:

“If we don’t get control over costs, then it is going to be very difficult for us to expand coverage,” Obama said. “These two things have to go hand in hand.”

Healthcare reform “is not a luxury” nor something that must be done because of his campaign pledge, Obama said.

“This is a necessity,” he said. “This is something that has to be done. Soaring health care costs are unsustainable for families, they are unsustainable for businesses, and they are unsustainable for governments … at the federal, state and local levels.”

He said projections indicated a fifth of the U.S. economy was projected to be wrapped up in the healthcare system in 10 years.

One of the ways to control escalating healthcare costs is by the choice of cost-effective treatments, and already right wing organisations are campaigning against the reforms with reference to the UK experience of NICE:

Conservatives for Patients’ Rights (CPR)—which is tied to sections of the US healthcare establishment and has spent millions of dollars on the adverts—has run weeks of the slots, showing doctors and patients ridiculing the UK and Canadian systems over waiting times for operations and the rationing of some treatments and life saving drugs.

CPR says that Obama’s plans to bring down the cost to the state and private insurance companies of the most expensive healthcare system in the world while extending access to about 45 million people without insurance—15% of the population—will result in rationing by the government. This they have likened to the UK National Institute for Health and Clinical Excellence (NICE).

“As our nation goes forward in its own healthcare reform debate, the failures of the British system should have Americans asking some very important questions, such as, ‘Who should make medical decisions—me and my doctor or a government board?’” CPR asks in one of the adverts shown on television stations throughout the US.

Interestingly, SourceWatch tells us that Conservatives for Patients’ Rights (CPR) is a front for a right wing organisation, whose previous form includes attacking John Kerry over his Vietnam war record during the 2004 US Presidential elections. The CPR attck on healthcare reform is extremely well funded, and led by Richard Scott. Maggie Mahar has some interesting background on Scott’s involvement in US healthcare as CEO of Columbia/HCA Healthcare Corp:

In July of 1997, the FBI swooped down on HCA hospitals in five states. Within weeks, three executives were indicted on charges of Medicare fraud, and the board had ousted Scott.

The investigation revealed that the hospital chain had been bilking Medicare while simultaneously handing over kickbacks and perks to physicians who steered patients to its hospitals. One can only wonder how many of those patients really needed to be hospitalized—and how many were harmed.
The company did not fight the charges. In 2000, HCA (which by then had expunged “Columbia” from its name) pleaded guilty to no fewer than 14 felonies. Over the next two years, it would pay a total of $1.7 billion in criminal and civil fines.

This is hardly a good position from which to criticise Obama’s healthcare reforms.

So, the attempt to create a US “NICE” to look at the relative cost effectiveness of medical interventions is seen feared by some, and invokes strong claims form others. Karol Sikora, a UK oncologist, says of this debate that:

There is a good reason NICE has attracted interest from U.S. policymakers: It has proved highly effective at keeping expensive new medicines out of the state formulary. Recent research by Sweden’s Karolinska Institute shows that Britain uses far fewer innovative cancer drugs than its European neighbors. Compared to France, Britain only uses a tenth of the drugs marketed in the last two years.

Partly as a result of these restrictions on new medicines, British patients die earlier. In Sweden, 60.3 percent of men and 61.7 percent of women survive a cancer diagnosis. In Britain the figure ranges between 40.2 to 48.1 percent for men and 48 to 54.1 percent for women. We are stuck with Soviet-quality care, in spite of the government massively increasing health spending since 2000 to bring the United Kingdom into line with other European countries.

[...]

The risks of America’s move toward British-style drug evaluation are clear: In Britain it has harmed patients. This is one British import Americans should refuse.

As a side issue, Karol Sikora, is described at that article as “a practicing oncologist, is professor of cancer medicine at Imperial College School of Medicine, London, and former head of cancer control at the World Health Organization.” The link with Imperial College is subject to dispute.

My colleagues Sarah McDowell and Prof Ferner from the West Midlands Centre for Adverse Drug Reactions have an editorial in the BMJ this week dealing with some of the attacks NICE and neatly describe the importance of cost-effectiveness.

We know this from cost-effectiveness analysis, which establishes whether one treatment is better than another, and if so, by how much—the marginal benefit—and how much has to be paid for the additional benefit—the marginal cost (see figureGo). For the past decade, NICE’s appraisal committees have been considering evidence from industry, doctors, and patients, and using it to provide independent estimates of cost effectiveness for the NHS.10 NICE compares the marginal benefit, measured (perhaps imperfectly) in quality adjusted life years (QALYs), and the marginal cost, in terms of money paid by the NHS and social services.

Treatments can be compared for different conditions. NICE generally accepts those interventions with a cost per QALY less than £20 000 as representing good value for the NHS. While it may also recommend other treatments, the chances of recommendation diminish as the cost per QALY increases. Once NICE has recommended a treatment, the NHS undertakes to fund it. NICE has endorsed full or restricted use for 84% of the treatments it considered, and encouraged research on a further 6% (Rawlins MD, NICE, personal communication).

NICE may decline to recommend costly treatments that bring tiny benefits—such as pemetrexed, which costs over £50 000 per QALY but adds a statistically non-significant 12 days to life expectancy in non-small cell lung cancer. Any unfavourable decision allows critics to deploy poignant tales of personal tragedy,11 often with exaggerated statements of potential health gain, without the counterbalance of tragic stories ensuing from unmet need elsewhere. The US initiative needs to provide data to support moves away from treatments that bring small marginal benefits for huge marginal costs and which fuel rapidly escalating healthcare spending without corresponding improvements in health. Market forces have failed to contain health expenditure in the US or to direct it towards effective treatments.12 This is partly because sensible decisions on medical care, whoever makes them, require information on comparative efficacy and cost effectiveness. The most useful data are unbiased, directly measured, and relevant to the individual. NICE represents the closest current approach to these ideals, and other countries have followed the UK’s lead.

Sir William Beveridge, who in 1942 set out the blueprint for the NHS, wrote: “The first principle is that any proposals for the future, while they should use to the full the experience gathered in the past, should not be restricted by consideration of sectional interests established in the obtaining of that experience.” Sectional interests are trying to defeat long overdue healthcare reform in the US, as they have tried to outflank NICE in the UK.

Like the UK’s health reform in the 1940s the US reforms are being attacked with cries of fascism, totalitarianism, and communism. Hopefully Obama’s reforms will pass, and it is likely that the reforms will be broadly accepted when it is seen that they have a beneficial effect on healthcare provision in the US. The right wing idealogues will be forgotten.

The issue of compulsory vaccination has been raised again.

A former chairman of the British Medical Association is calling for the MMR jab to be made compulsory.

Public health expert Sir Sandy Macara believes children should not be able to go to school unless they have first been vaccinated.

I have mixed feelings on this. The dangers of a measles epidemic are very real. However, compulsory vaccination does play into the conspiracy theories of the anti-vaccine movement, thus perpetuating one of the reasons that vaccines may be avoided by some. This is a point made by Professor Finn in the BBC news article.

Professor Adam Finn, a vaccine expert in Bristol, said the media was largely to blame for scaremongering over the MMR jab.

But, although he sympathises with Sir Sandy’s concerns about the possibility of a measles epidemic, Professor Finn believes compulsory vaccination would be counter-productive.

“There is a real risk we would end up with less MMR immunisation not more,” he said.

“I think this would be handing a gift to the anti-vaccine lobby, because they would say ‘look they can’t persuade you it is right, so they are going to have to force you’.”

I think we ought to be careful about the use of the term compulsory.

The idea that children cannot go to a school unless a vaccination certificate is provided is fine, but why not allow medical exemptions and some philosophical and/or religious exemptions (This is the situation in US states and in the US immigration service).

That would make opting out of vaccines an active choice, rather than a passive decision.

It would not make vaccines completely compulsory though, and reduce the opportunity for the accusations of fascism and totalitarianism that Sandy Macara raises in his defence of his idea. It is not clear whether Macara’s suggestion includes a vaccination waiver.

Sarris, J., Kavanagh, D., Byrne, G., Bone, K., Adams, J., & Deed, G. (2009). The Kava Anxiety Depression Spectrum Study (KADSS): a randomized, placebo-controlled crossover trial using an aqueous extract of Piper methysticum Psychopharmacology DOI: 10.1007/s00213-009-1549-9

The Pharmaceutical Journal recently reported on a study, published online in the Journal of Psychopharmacology, with the headline Banned kava safe and effective at reducing anxiety. The study gets some coverage in the media, where the lead author, a PhD candidate from the University of Queensland’s School of Medicine, states the following:

“Our study used a water-soluble extract from the peeled root stock of a medicinal cultivar of the plant, which is approved by the Therapeutic Goods Administration,” Mr Sarris said.

“When extracted in the appropriate way, kava may pose less or no potential liver problems (and) I hope the results will encourage governments to reconsider the ban.”

The ban Mr Sarris is talking about is one that came into being in the UK in 2003, following reports of serious liver toxicity associated with Kava. Here is a letter I submitted to the The Pharmaceutical Journal in response to their news report, which also addresses the claims Sarris makes about the safety of Kava - based on his trial.

The Pharmaceutical Journal recently reported (PJ, 16 May 2009, p577) that the herb kava was “safe and effective at reducing anxiety” on the basis of the small (n=60) three-week placebo-controlled, crossover trial “the kava anxiety depression spectrum study” (KADSS).¹

The Journal reported “the study authors note that the aqueous extract was safe, with no liver toxicity or other serious adverse effects”.

Kava was prohibited in the UK in January 2003. The Committee on Safety of Medicines (CSM) judged that it “posed a rare but serious risk to public health” following reports of idiosyncratic liver damage. A July 2006 report of the CSM’s Expert Working Group on the safety of kava concluded that the prohibition order was justified and proportional.²

Liver damage ranged from mild jaundice or changes in liver function to more serious cases of hepatitis and liver failure. Eleven patients required liver transplants and nine individuals died as a result of the hepatotoxicity. No specific susceptibility factor was identified, such as gender or age group.

There is debate about the relative safety of differing cultivars of kava and the differing extraction methods (aqueous, acetonic and alcoholic).³ A World Health Organization assessment of the risk of hepatotoxicity associated with kava noted that acetonic and alcoholic extracts may be risk factors for hepatotoxicity and should be avoided.⁴ The KADSS study used an aqueous extract of the “noble” cultivar of kava.

However, the WHO assessment notes five cases of hepatotoxicity associated with aqueous extracts of kava,⁴ and there are published case reports of hepatotoxicity with traditional aqueous preparations.⁵

Additionally, given the onset time of kava-associated hepatotoxicity in reported cases, with most occurring within three months of treatment initiation (ranging from immediate to many months), a three-week study does not give opportunity for such reactions to develop.

More importantly, even if an event has not occurred, this does not mean it cannot happen. Using the rule of three,⁶ we can calculate that we can be 95 per cent confident the incidence of an adverse event that did not occur within the trial would lie between zero in 60 cases and three in 60 cases. This means that hepatotoxicity occurring with a frequency as high as one in 20 patients could remain undetected by the KADSS study.

Given that kava-associated hepatotoxicity is a rare reaction, the KADSS study does not provide any meaningful safety information about kava or the relative safety of differing extraction methods. Headlines suggesting kava is safe on the basis of this study are, therefore, misleading and dangerous.

You can read the KADSS study online here, where you can learn that one of the authors is a consultant to MediHerb Pty Ltd who supplied the tablets, although “He was not involved in the conduct of the study or the analysis of the data.” Mr Sarris also states in another news article:

“Allowing the sale of kava in Europe, the UK and Canada would significantly enhance Pacific island economies, which have lost hundreds of millions of dollars by not being able to export the plant over the past several years,”

Which may or may not sway your views on the safety of Kava.

Herbs, unlike homeopathy, can be pharmacologically active compounds with potent effects. They can also cause toxicity. In that respect they can be treated as any other pharmaceutical product. If a pharmaceutical company with a drug withdrawn because of reports of hepatotoxicity attempt to relaunch it with a study in 60 patients, they wouldn’t have a chance of a reassessment. They would be told to go away and design a study that addressed the safety issue properly.

Just because something is natural does not mean it is safe.

References

[more...]

I’ve been blogging about MMR vaccine since I started this blog in about February 2003 over 5 years ago, long before it was fashionable to do so. To be frank, I have to a large extent grown weary of doing so, but even prior to blogging I used to argue with the anti-vaccinators on various internet newsgroups (remember them?). There was a time when anti-MMR vaccine views even appeared in my professional journal, I wrote two letters at the time (back in 2002).

Overwhelming evidence for safety of MMR and Childhood vaccination, a social responsibility.

The latter letter included the following:

The decision of a patient not to use a medicine usually has little direct effect on the health of other individuals, but the denial of vaccination puts others at risk. Some of those at risk will not have had the opportunity to obtain vaccination, for example, small infants below the age of vaccination will be at risk.

The Department of Health’s policy towards MMR is based on current scientific advice. If the Government were to ignore scientific advice this would be a truly regressive step. There is evidence that the provision of single vaccines may reduce uptake, thereby increasing the prevalence of measles. In addition some polls already show concerns are not limited to MMR, with 4 per cent of parents with young children not wishing to inoculate their children against mumps, measles or rub-ella by either single vaccines or use of MMR. Changing government policy for short-term political gain, rather than because of scientific evidence, would be seen by some as a tacit admission that a link between autism and measles vaccine exists, when no evidence supports such a risk.

Partnership is needed with parents and the public in putting across the safety and importance of the MMR vaccine, but the consideration of NHS provision of single vaccines needs to be seen as a public health issue.

Seven years on, the fruits of the credulous scaremongering media and the anti-MMR vaccine movement, which is clearly a crank anti-vaccine movement now although it arguably wasn’t at the time, are all too clear. People in intensive care units, and the potential for preventable childhood deaths from measles.

Health chiefs fear one of the biggest measles outbreaks in Wales will become fatal after figures showed 207 people are suffering from the virus.

Several people have been treated in intensive care units after the worst outbreak of the disease in years.

Here we have a disease spreading in Wales which has killed children in the past, and for which we have an effective vaccine. We are meant to to be in the grip of a panic about Swine flu.

How about a panic about measles first?

We at least have an effective vaccine for that.

I have a new article in The Pharmaceutical Journal published with a colleague Dr Deborah Layton looking at the neuraminidase inhibitors oseltamivir and zanamivir.

Cox A, Layton D. Adverse drug reactions: Neuraminidase inhibitors: widespread use for influenza may reveal more adverse effects. The Pharmaceutical Journal 2009; 282:621-622

The neuraminidase inhibitors (NAIs), oseltamivir (Tamiflu) and zanamivir (Relenza), are indicated for prophylaxis and treatment of influenza.

Both antivirals are included within the current UK Health Protection Agency guidance for the treatment and prophylaxis of infection from the novel swine influenza A (H1N1) virus. These drugs are more effective and safer than older antivirals, such as the amantanes (amantidine and rimantadine).

In the event of a global pandemic the NAIs will be administered to a large proportion of the population.

The full article is here. You have to register to read it.

A large part of the article deals with the issue of potential neuropsychiatric reactions. In Japan, a country that consumes vast quantities of oseltamivir routinely, neuropsychiatric effects have been widely reported in the media for a number of years, with particular concern about suicide attempts, however the casuality is unproven.

This morning I was at the Royal Pharmaceutical Society of Great Britain’s Branch Representative meeting representing the Birmingham and District branch. It’s a yearly meeting, and an opportunity for the local branches of the organisation to pass motions which can be used to steer the organisation. One of the motions, submitted by the Slough and District branch, was the following:

It is the opinion of this meeting that the Society should produce a position statement stating that registration as a pharmacist and practice as a homeopath are not compatible, and that premises registered with the Society should not be used for the promotion of homeopathy.

The motion was effectively requesting that homeopathy should not be promoted by pharmacists and not sold in pharmacy shops. Dr Angela Alexander, a friend, gave an excellent introduction to the motion, and the motion was effectively seconded. I thought the motion would pass easily. I spoke briefly from the podium:

How embarassing that such a motion has to be raised in this forum.

But how necessary it is.

The background provided by Council gives enough evidence to condemn our profession.

Over 50% of homeopathy sales are made by pharmacies.

Pharmacists specialise as homeopathy specialists.

Pharmacists provide trainign course on homeopathy.

Pharmacists manufacturing and wholesaling homeopathy products.

As a profession that has promoted itself as the scientist in the high street, and which requires a four year science degress, how can we associated with homeopathy? A form of quackery based on implausible principles, which has been shown to have absolutely no therapeutic effect. Are we to be the quack in the high street?

Pharmacists are experts in medicines, purveyors of evidence based therapeutics, prescribers, and play a crucial role in medicines management at a local and national level. Do we really want to be associated with people who have reccomended placebo pills for prophylaxis for malaria?

We should also not hide behind the MHRA’s decision to regulate homeopathic medicines. That controversial decision may have arguably been taken for pragmatic reasons to prevent the worse examples of homeopathy, but it should not be seen as a scientific endorsement. As a scientific profession we should stand for truth and as a caring profession we should not exploit our patients.

I urge you to support this motion.

It wasn’t exactly tumbleweed when I finished, but the following speaker who talked about having an “open mind” and suggested that selling homeopathy gave opportunities for pharmacists to interact with patients and provide sensible advice got a much better reception. Suddenly, it seemed obvious that the room was not in favour of the motion. Another speaker argued that attempting to tell pharmacists they should not sell homeopathy was another attempt to over-regulate the profession, taking away professional freedom.

Embarassingly, the motion was lost.

The Chemist and Druggist noted before the debate:

the motion was condemned by London pharmacist and homeopath Tony Pinkus, who said it was “not based on anything other than prejudice as far as I
can gather”.

Prejudiced? Prejudice is a bias, which happens to be the very thing that clinical trials attempt to control. It is evidence from trials that has shown that homeopathy does not work. Being against homeopathy is a judgement based on evidence, not a prejudice. It is the opponents of this motion who are prejudiced, in favour of homeopathy despite the overwhelming evidence against it.

What a state of affairs. We will continue to see members of a scientific profession promoting homeopathy. Christine Glover was President of the Royal Pharmaceutical Society of Great Britain from 1998-2001, something she is proud on her website. This is the sort of material on her website:

Christine Glover is a very well known pharmacist with homeopathic training offering an holistic integrated approach to healthcare. She neither rejects conventional medicine nor accepts alternative medicine uncritically. She believes that emotional happiness is a fundamental part of physical health for an all round sense of balanced wellbeing.
[...]
Homeopathy for Children and Pregnant Mothers
Christine Glover can help with your children, offering homeopathic solutions for a wide range of common problems. For example, infant colic, teething, endless runny noses, hyperactivity, poor sleep, restlessness and bedwetting are all common problems which can be helped.

We are also able to offer a homeopathic support package for pregnancy and childbirth.

She is also setting up a network for pharmacists to work with The Foundation for Integrated Health, Prince Charles’ alternative medicine organisation which has attracted criticism. Here are Glover’s thoughts on what good pharmacists are doing:

This sort of approach [integrated medicine] is what every good pharmacist is probably doing already to a greater or lesser extent. Most community pharmacies carry some products which fall into the complementary category: herbals, homoeopathic remedies, magnetic bracelets etc.

Good pharmacists are flogging magnetic bracelets? One can only imagine the horrors hidden behind that “etc”.

David Colquhoun will not be happy. Nor will Edzard Ernst.

There is some good news. Branch Representatives Motions are not binding. The Council of the RPSGB does not need to follow them. Secondly, the RPSGB is currently both a regulator and a professional body (a bit like the GMC being combined with the BMA in one body). By this time next year, the two roles will be split and the new professional body will not have to follow this motion either. Hopefully the new professional body will attract pharmacists who can see that it is unprofessional to continue to sell a product that is so clearly quackery. On the negative side, the professional body will not be able to force pharmacists to stop selling homeopathy.

I have written a brief review of patient reporting of adverse drug reactions by patients for Pharmacovigilance Review. It’s not a systematic review, but I think it is a reasonable review of current knowledge. The PDF is here.

BBC news 8pm Radio 4 reported on the case of a school with a suspected case of Swine flu. The brief report ended with the following.

“The child and his 24 classmates are being treated with the vaccine Tamiflu”

Arrghhhh!