Questions raised about industry influence on anti-depressant studies
For more than two decades, researchers have been unable to settle an important question: Can anti-depressant medications stimulate the growth of breast and ovarian cancers?
Some studies pointed to a link, but others did not.
Now a re-examination of the available evidence has cast a new – and disturbing – light on the previous research. Many studies that seemed to absolve the drugs of blame were carried out by researchers with close ties to the pharmaceutical industry, according to a report published this week in the online journal PLoS (Public Library of Science) One.
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“I think that’s an important piece of information,” said the lead author of the paper, Lisa Cosgrove of the Edmond J. Safra Center for Ethics at Harvard University in Boston.
For the review, Dr. Cosgrove and colleagues amassed a total of 61 studies, which included both laboratory and epidemiological research.
They then conducted separate searches on the principal investigators for each of the studies, looking for drug-company connections. “It was a lot of legwork,” said Dr. Cosgrove, noting that, in the past, such ties were not always publicly reported.
A clear pattern emerged. “None of the researchers with industry affiliation reported a positive association” between antidepressants and the risk of cancer, she said.
There were more mixed findings among researchers free of corporate ties. “Approximately 43 per cent of researchers without industry affiliation reported a positive association.”
A closer examination of these studies – using meta-analysis, which pools the data – suggests the risk is real, but not very large. Women with a history of antidepressant use faced an 11-per-cent increased chance of developing breast and ovarian cancer, compared with those who had not taken these medications. In the case of breast cancer, that means taking antidepressants would raise an average woman’s lifetime risk to 13.8 per cent from 12.5 per cent, Dr. Cosgrove said.
The risk is primarily associated with just one class of antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, which includes Prozac (generic name, fluoxetine), Paxil (paroxetine) and Zoloft (sertraline). “All studies but one in the SSRI analysis found a positive association,” she said.
Tricyclics, an older class of drugs, don’t appear to be as problematic. “There was a slight increase in risk but it was not statistically significant,” she said.
“I wouldn’t want any woman who is taking an antidepressant to abruptly stop,” cautioned Dr. Cosgrove. “She should talk over that decision with her doctor.”
Although the drugs appear to boost the odds of getting cancer by only a small amount, she said women should at least be informed of the potential risk. And that risk doesn’t come to light in industry-connected studies.
“We are at a point where public trust in biomedicine is rapidly decreasing as a result of conflicts of interest.”
However, Dr. Cosgrove doesn’t believe there is some covert “Machiavellian” plot by industry to cover up all unfavourable study results. She noted that the vast majority of researchers who receive industry funding consider themselves to be unbiased.
Over time, though, close industry ties can have a “pernicious” effect on the attitudes and actions of doctors and scientists. “Researchers might not be aware of the subtle ways they can be influenced, “ she said.
Doctors could be allowed to prescribe cheap drugs
In a move that could benefit many patients currently denied expensive treatments, the regulator for the medical profession has said for the first time that GPs should be allowed to give out a less costly alternative even if it is not licensed for that condition.
The General Medical Council said that doctors must only check that the “off-label” drug is safe and effective, as well as telling their patients why they are prescribing it.
It could bring fresh hope to thousands of people who suffer from the leading cause of blindness, wet age-related macular degeneration (wet AMD), who are currently denied treatment because one drug is extremely costly and because pharmaceutical companies will not seek a licence for a cheap alternative.
The updated GMC guidance also warns GPs of the potential risks of prescribing treatments by telephone or over the internet, and tells them to consider raising concerns if they believe athletes are using performance-enhancing drugs.
Niall Dickson, the Chief Executive of the GMC said: “Between 1995 and 2009 the number of drugs prescribed by GPs tripled and it is clear that they remain a vital part of the medical armoury, bringing benefits to many patients.
“So it is vital that our guidance for doctors on prescribing and managing medicines is relevant and up to date.”
Drugs are licensed for specific conditions by one quango called the Medicines and Healthcare products Regulatory Agency, and then another body called the National Institute for Health and Clinical Excellence (Nice) draws up guidelines on whether or not they should be recommended for general use of the NHS.
But pharmaceutical firms have been accused of failing to seek additional licences for products that can treat more than one condition, in order to protect their profits.
In the case of wet AMD, with which 20,000 people are diagnosed every year in Britain, there is a licensed and recommended treatment called Lucentis that costs around £750 a dose.
Another drug called Avastin, which can cost as little as £50 a dose, is also effective in stopping sufferers losing their sight, yet is licensed for bowel cancer but not for wet AMD.
Some health trusts in England have already started using Avastin instead of Lucentis for the eye condition, and now the GMC has suggested that it is willing to allow all doctors to do so.
Its new draft guidance states: “You should usually prescribe licensed medicines for their licensed uses; but you may prescribe off-label or unlicensed medicines outside an approved research protocol if there is no appropriately licensed alternative available or you are satisfied, on the basis of authoritative clinical guidance, that it is as safe and effective as an appropriately licensed alternative.”
The GMC highlights two drugs effective for treating anxiety and pain, for which “there are licensed alternatives, but they are not considered by Nice to be as cost-effective”.
The document also raises concerns about the increasing number of doctors prescribing drugs “remotely” – by phone or online – although it does not outlaw the practice .
It states: “You should prescribe only when you have adequate knowledge of the patient’s condition, and are satisfied that the medicines serve the patient’s needs.
“You should consider the limitations of the medium through which you are communicating with the patient, the need for physical examination or other assessments and whether you have access to the patient’s medical records.”
The consultation document goes on: “Many respondents to the scoping consultation to develop this draft were in favour of a ‘ban’ on doctors prescribing remotely (particularly online) for patients they had not met and whose records they did not have access to, especially without liaison with the patients’ general practitioners.
“Others questioned the evidence of harm arising from online and other remote prescribing practices. A few were concerned about the impact any ‘ban’ might have on patients’ access to the medical care of their choosing and their rights to control information about themselves.”
New drugs from mutant bugs
Working with Japanese pharmaceutical company Daiichi-Sankyo, and funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC), the researchers’ work paves the way for the creation of new hybrid antibiotics that may help to solve the growing problem of bacterial infections that are resistant to essentially all antibiotics.
The research is published online in the journal PLoS ONE.
The team, comprising microbial geneticists from Birmingham and chemists from Bristol, determined the sequence of the complete DNA content of the marine bacterium that produces the new antibiotic, thiomarinol, owned by Daiichi-Sankyo. They then identified the genes responsible for making the antibiotic on the basis of their similarity to genes that make the related but less potent antibiotic, mupirocin, which is currently used to combat MRSA (methicillin resistant Staphylococcus aureus).
They found the genes are on a relatively small, separate DNA molecule called a plasmid, which is just big enough to carry the genes for making the antibiotic plus genes to allow the plasmid to replicate autonomously in the bacterium. The plasmid thus carries genes that make both the mupirocin-like antibiotic as well a second antibiotic, holomycin, and a gene responsible for joining both antibiotics together, forming a more potent molecule.
Tests showed that by joining the antibiotics together the resulting chemical is able to inhibit the growth of MRSA strains that have become resistant to mupirocin. ‘This shows how mupirocin can be modified to make it more potent and suggests that related molecules could be used against the increasingly problematic Enterobacteriacae like Escherichia coli and Klebsiella pneumoniae,’ says University of Birmingham research lead Professor Chris Thomas.
By using mutant strains that were unable to make either the mupirocin part or the holomycin part the team was able to feed alternative compounds to the bacteria – so-called mutasynthesis – so that a family of novel molecules was created, and tests showed some of these had biological activity. ‘This provides hope that the system will allow the production of new antibiotics that may help to combat the growing problem of antibiotic resistance in pathogenic bacteria,’ adds University of Bristol research lead Professor Tom Simpson.