Infectious diseases – Helen Jaques

Infectious diseases, Pharmaceutical industry

Tamiflu isn’t much good and Roche tried to stop us showing so, says the BMJ

December 9, 2009 1 Comment

The BMJ has just published a whole slew of papers about Tamiflu (oseltamivir) – a key drug in the public health response against swine flu (influenza A/H1N1).

The linchpin is a Cochrane review on the efficacy of neuraminidase inhibitors – namely zanamivir (Relenza; Glaxo Wellcome) and oseltamivir (Tamiflu; Roche) – for preventing and treating influenza in healthy adults. The review found that these two drugs were only partly effective against laboratory confirmed symptomatic influenza (oseltamivir 61% effective; zanamivir 62% effective), and no good at all against asymptomatic flu or flu-like illness.

In addition, Tamiflu did not reduce the risk of influenza-related lower respiratory tract complications – bad news for the Department of Health, which recommends using the drug to prevent secondary complications in healthy adults. The authors conclude: “Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza.”

In an accompanying feature, Deborah Cohen retraces the steps leading to the publication of the Cochrane review and highlights all the difficulties the authors had extracting data from Roche, the makers of Tamiflu. The review “exposed a complex interplay between politics, public health planning, availability of trial data, publishing, and drug regulation.”

Turns out that Roche’s claims that Tamiflu reduces hospital admissions and secondary complications of influenza were based on a 2003 meta-analysis that only included two proper randomised controlled trials and was authored by several Roche employees. When the authors of the Cochrane review tried to get their hands on the data in this paper to include them in their own analysis, they came up against all sorts of obstacles thrown up by Roche.

Peter Doshi, an author of the new Cochrane review, writes in the BMJ of his struggle to get hold of the elusive data and offers a damning verdict on the use of the drug in the swine flu epidemic. “Since August 2009, our Cochrane review team has tried to obtain the data needed to verify claims that oseltamivir (Tamiflu) lowers serious complications of influenza such as pneumonia. We failed, but in failing discovered that the public evidence base for this global public health drug is fragmented, inconsistent, and contradictory. We are no longer sure that oseltamivir offers a therapeutic and public health policy advantage over cheap, over the counter drugs such as aspirin.”

In an analysis article, Nick Freemantle and Mel Calvert look over the observational studies of Tamiflu that Roche cited in defense of their claims for the drug and found that they also do not support the use of Tamiflu to treat influenza in healthy adults. In their discussion they write: “oseltamivir may reduce the risk of pneumonia in otherwise healthy people who contract flu. However, the absolute benefit is small, and side effects and safety should also be considered. None of the studies examined the role of oseltamivir in patients with H1N1 influenza, which may be associated with higher rates of pneumonitis than seasonal influenza.”

Finally, in a linked editorial, Fiona Godlee, editor of the BMJ, and Mike Clarke, director of the UK Cochrane Centre in Oxford, rail against the obstructive techniques used by Roche and call for full data from clinical trials to be made available to the scientific community. “Why should the public have to rely on detective work by academics and journalists to patch together the evidence on such a potentially important drug?” they ask.

All this is bad news for public health planning against swine flu – the Department of Health has already stockpiled more than 30 million doses of potentially useless Tamiflu – and even worse news for Roche.

For a good summary of the Cochrane review, have a look at the Best Treatments guide on the Guardian website.

———————————————————————————————–
Jefferson T, Jones M, Doshi P, & Del Mar C (2009) Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis. BMJ 339 DOI: 10.1136/bmj.b5106

Infectious diseases, Journals

So what happened to the AIDs vaccine?

October 26, 2009 No Comments

You might remember all the hullabaloo last month about the HIV vaccine developed by the US military and tested on 16,000 people in Thailand. Hailed as an “HIV breakthrough” and a “historic milestone“, the initial press release of the study certainly had the media convinced that a prevention for AIDs was just around the corner.

Now the research has been presented in full at the AIDS Vaccine 2009 Conference in Paris and in the New England Journal of Medicine, and reactions are far more circumspect.

Granted, the vaccine in question is the first ever to provide any kind of protection against HIV, but it only prevented HIV-1 infection in 31.2% of participants. 74 of the 8198 volunteer who received the placebo vaccine became infected with HIV-1, but 51 of the 8197 people who were given the vaccine still managed to get infected – a difference of only 23 people.

I’m not really sure what happened with this story. Did it get press released before publication and before anyone had a good look at all the data? To be fair the initial news stories were pretty good in their reporting of the research, but why is the story doing the rounds again?

New Scientist is on the ball with this. In September they published an article “What to make of the HIV vaccine ‘triumph’“, in which they point out that “the victory was won by the slenderest of numerical margins.”

In addition, New Scientist provides some sort of answer to my previous question. Says the article: “The result was disclosed at the earliest available opportunity at the request of the Thai collaborators, says Merlin Robb, deputy director for clinical research at the MHRP. “The Thai Ministry of Public Health was very anxious to let the volunteers in Thailand know the result as soon as possible, instead of waiting for a scientific conference,” says Robb. “This reflects our commitment to the volunteers and transparency in all aspects of this trial,” he said.”

So what’s with this jumping of the gun and presenting research before it’s been published in a peer review journal? But researchers live in a “publish or perish” environment and are in constant fear of being “pipped to the post”.

The BMJ says “We do not want material that is published in the BMJ appearing beforehand, in detail, in the mass media” and “The BMJ does not want to publish material that has already appeared in full elsewhere“. And the New England Journal of Medicine cites their “Ingelfinger rule“, which “requires that author-researchers not release the details of their findings to the mass media before their work undergoes peer review and is published.”

I don’t think this research would have subsequently been published in the NEJM if the authors had in fact broken the embargo, so there must have ben some intense behind the scenes bargaining to get the paper released early – but only a month early.

I’m not really sure what point I’m trying to make here, but I think it’s certainly interesting that this paper made a bug splash a month before the full data was published then did the rounds again.

Infectious diseases

Junior doctors pressed into taking HIV tests

July 17, 2009 1 Comment

Blood test Junior doctors are undergoing HIV tests as part of pre-employment occupational health checks without being made aware that such testing is not mandatory, according to research published in the Journal of Medical Ethics. Many junior doctors interviewed by Lee Salkeld and colleagues held the misperception that HIV testing was compulsory and felt unable to decline the test. In addition, interviewees felt that they had not been provided with enough information about the test or about the impact of a positive result.

According to guidance published by the Department of Health in 2007, all new healthcare workers need to undergo tests for tuberculosis and hepatitis B, and should be immunised as necessary. Only those who will perform exposure-prone procedures – i.e. people who will undertake invasive procedures where there is a risk that the patient’s open tissues could be exposed to the blood of the worker – are required to have an HIV test.

Several of the 24 juniordoctors (foundation years 1 and 2)and doctors in specialty training (years1, 2 and 3) interviewed by Salkeld et al., however, commented that the requirement of an HIV test was simply presented as just another part of a long list of tests that were necessary.

This lack of pre-test discussion meant that most of the doctors were unclear about the implications of a positive HIV test. One even asked: “I wonder if they’d have sacked me if it was positive. No one really explained what would happen if it were positive either—would my bosses have been told about it?”

The DoH guidance suggests that healthcare workers could benefit from these regulations “both personally and professionally”. Most of the junior doctors interviewed by Salkeld et al. thought that HIV testing was for the benefit of patients, though; few mentioned the benefit to themselves of knowing their HIV status and being able to access treatment should they be HIV positive.

There have been only two cases of HIV transmission from doctors to patients worldwide – one involving an orthopaedic surgeon and the other an obstetrician, neither of whom were practising in the UK. The risk of HIV transmission from healthcare worker to patient is eximated to be between 1 in 42,000 and 1 in 420,000, although the risk of patient-to-doctor transmission is 1 in 300.

Given these figures, the authors ask “is this somewhat utilitarian Department of Health policy justifiable?”
————————————————————————————————
Salkeld L et al. (2009) HIV testing of junior doctors: exploring their experiences, perspectives and accounts Journal of Medical Ethics 35 (7): 402-406. DOI: 10.1136/jme.2008.027052

Infectious diseases, Technology

A gr8 way to ensure adherence to tuberculosis medication

April 2, 2009 1 Comment

An ingenious new system has been developed to make sure that patients with tuberculosis (TB) complete their entire course of treatment, thus preventing the emergence and spread of drug-resistant forms of the disease.

TB urine test XoutTB involves a paper strips embedded with chemicals that detect metabolites of the TB drug isoniazid in a patient’s urine. The strips contain four printed numbers, a certain combination of which react and turn a new colour when exposed to the urine of patients who have taken their medication.

Patients then send a mobile phone text message reporting the numbers on their strip to a central database. Those patients who take the drugs consistently for 30 days are be rewarded with cell-phone minutes.

TB is a preventable but potentially deadly bacterial infection that kills almost 2 million people each year. Rates of TB have increased since the 1980s, in part due to the emergence of drug-resistant strains of the TB bacteria.

Drug resistance is a serious barrier to effective treatment of TB and to the permanent eradication of the disease, so serious that the World Health Organisation this week called the problem “a potentially explosive situation”.

Drug-resistant strains of TB emerge when the antibiotic used to treat the infection fails to kill all of the bacteria it targets. The surviving bacteria become resistant to that particular drug and pass this characteristic on to their descendants, thus spreading the trait.

The major cause of TB drug resistance is inadequate treatment, either because the wrong drugs are prescribed or because people don’t take the entire six-month course of medication. In particular, TB medication has considerable side effects, so to many individuals there seems little incentive or personal gain to be had from taking the whole course of medication.

The new monitoring system, developed by José Gómez-Márquez and colleagues of the Innovations in International Health program at Massachusetts Institute of Technology, provides a clear monetary incentive to encourage patients to take the medications that will improve their health and also indirectly benefit the health of others.