Dear Colleagues! This is Pharma Veterans Blog Post #324. Pharma Veterans welcomes sharing of knowledge and wisdom by Veterans for the benefit of Community at large. Pharma Veterans Blog is published by Asrar Qureshi on WordPress, the top blog site. Please email to firstname.lastname@example.org for publishing your contributions here.
Why do apparently responsible and respectable researchers commit data fraud? Studies have been conducted to ascertain reasons. One common factor would be personal gain either financially or in terms of enhanced image or gaining of a higher position.[Quote] “Davis, et al.  analyzed 92 cases from the ORI in which the respondent was found to have committed scientific fraud. Starting with 44 possible factors implicated in scientific misconduct, the authors used multidimensional scaling and cluster analysis to define a few clusters of similar factors labelled as personal or professional stressors (e.g., pressure to produce), organizational climates (e.g., insufficient supervision/mentoring), job insecurities (e.g., competition for position), rationalizations (e.g., lack of control) and personality factors (e.g., laziness). The net effect is to provide a complex picture of the motivations for those who commit scientific fraud. Continued research into the causal factors is important and may help inform more rational preventive measures.” [Unquote]
We move to the other relevant area of Pharmaceutical Companies’ role in manipulating drug trials. I shall quote from an article by Jeremy Laurance (@jeremylaurance) published in the INEPENDENT UK (link below).[Quote] “The multibillion-pound global pharmaceutical industry is accused today of manipulating the results of drug trials for financial gain and withholding information that could expose patients to the risk of harm.
The stranglehold that the industry exerts over research is causing increasing alarm in medical circles as evidence emerges of biased results, under-reporting and selective publication…
In cancer, heart disease, mental health and related fields the industry has sponsored trials of new drugs which have held out great promise for patients. But when the same drugs have been tested in independent trials paid for by non-profit organisations – governments, medical institutions or charities – they have yielded different results.
Heart drugs prescribed for abnormal heart rhythm introduced in the late Seventies were estimated to kill more Americans each year by 1990 than the Vietnam War. Yet early evidence which suggested the drugs were lethal, and might have saved thousands, went unpublished.
Expensive new cancer drugs introduced in the last decade and claiming to offer major benefits have increasingly been questioned. Evidence published in the Journal of the American Medical Association showed that 38 per cent of independent studies of the drugs reached unfavourable conclusions about them, compared with just 5 per cent of the studies funded by the pharmaceutical industry.
In the latest case, researchers commissioned by the National Institute for Clinical Excellence (Nice) to develop guidelines for prescribing antidepressant drugs to children, say they were refused access to unpublished trials held by the pharmaceutical companies.
Published evidence suggested that the antidepressant drugs called SSRIs (selective serotonin re-uptake inhibitors) were safe and effective for children.
But when researchers obtained the unpublished evidence by contacting individual researchers who had worked on the trials, a picture emerged of increased risk of suicidal ideas and attempted suicide. Only one drug, Prozac, was safe.
Antidepressants, though not recommended for children, were widely prescribed until last year when the Medicines and Healthcare Products Regulatory Agency (MHRA) issued a warning to doctors, prohibiting their use. This followed safety concerns raised by campaigners and taken up in two BBC televisionPanorama broadcasts.
Writing in The Lancet, the authors say: “On the basis of published evidence alone, we could have considered at least tentatively recommending use of these drugs for children and young people with depression. However, our review of combined published and unpublished data … suggest that these SSRIs are not efficacious. Moreover a possible increased risk of suicidal ideation, serious adverse events or both, although small, cannot be ignored.”
Tim Kendall, from the Royal College of Psychiatrists, said the researchers had been “unnerved” by the possibility that Nice could have issued wrong or harmful advice because it did not have access to the full data.
The same concerns would apply to advice issued about other drugs in other specialist areas, he said. Guidelines were being drawn up for the use of antidepressants in adults based on 1,000 published trials but it was possible there were tens or hundreds of unpublished trials they had not seen.
The Lancet says the possibility that the suicide of a child could be provoked by a supposedly beneficial drug would be a “catastrophe” and the idea of the drug’s use being based on “selective reporting of favourable research” should be “unimaginable.” It says the story of research into SSRIs in childhood “is one of confusion, manipulation and institutional failure.”
It cites an internal GlaxoSmithKline memo, published in the Canadian Medical Association Journal last month, referring to a study of the antidepressant Seroxat (paroxetine) in children. The memo said: “It would be unacceptable to include a statement that efficacy had not been demonstrated, as this would undermine the profile of paroxetine.”
Andrew Dillon, chief executive of Nice said: “The institute’s ultimate objective is to be given and to be able to use freely all data relevant to the guidance which it is asked to develop. We continue to work to that objective.”
The Association of the British Pharmaceutical Industry said it was prevented under Nice’s rules from supplying unpublished data for the preparation of clinical guidelines. But, it has set up a register of clinical trials, and regulations to be introduced next month under the European clinical trials directive would make monitoring easier”. [Unquote]
We have seen cases of several drugs being withdrawn due to serious side effects in our tenure in Pharma. Rofecoxib (Vioxx®) became a blockbuster before it was withdrawn. Closely related Celecoxib (Celebrex®) got the scare but was spared. Terfenadine (Teldane®) was introduced as the first non-sedative antihistamine over thirty years ago. The WHO kept monitoring the deaths caused by Terfenadine but did not stop its use. Finally, fexofenadine, a closely related compound was introduced and terfenadine was withdrawn. Other compounds of the same family of antihistamines are also not entirely safe but are selling. Gatifloxacin was withdrawn before it became a big drug. Cisapride (Prepulsid®) was touted as the most effective gastroprokinetic drug and became almost instantly popular. Deaths caused by QT prolongation forced withdrawal worldwide. Abbott withdrew Temafloxacin due to serious side effects. There are several drugs like lomefloxacin which have silently left the market due to side effects and went into oblivion. Some drugs are implicated but still selling, such as nimesulide and ebastine.
Our doctors appear have a strange affinity for withdrawn drugs. During early 1980s, Hoechst had introduced an antidepressant drug nomifensine (Merital®) amid lot of fanfare. In about two years, the drug had to be withdrawn due to increased deaths. The company informed the medical community and recalled all stocks from market. Some chemists and doctors refused to return the stock saying they would keep selling/prescribing it. Another such case was gatifloxacin. The Ministry of Health called a meeting of registration holders of gatifloxacin and it was agreed to stop production and sales immediately. Available raw material and finished stock had to be destroyed. Gatifloxacin demand kept coming from various quarters and I understand the last pack and last gram of material was finally consumed.