BP Oil Spillage Estimator
Using the estimation method outlined in our
June 14 article, we estimate the total oil spillage to date to be approximately
million barrels if the maximum flow was 100,000 barrels per day, or 6.5 million if it was 80,000 barrels per day. Note that the flow is currently stemmed while BP conducts tests on a new cap.
A Grim Reminder: 40,000 and Counting
President Obama signed the second part (reconciliation) of the health care reform bill on March 30, 2010. That's great, but the provisions that will cover the uninsured haven't clicked in yet.
Our elected officials started work on the proposed health insurance reform bill on July 30, 2009. Harvard researchers estimate that 122 Americans die every day as a result of not having health insurance.
So, the estimated number of uninsured Americans who have died while the politicians in the Senate and Congress played politics and delayed new benefits for the sake of the health care insurers is
today.
Bad Science - How the Big Pharmas Manipulate Drug Trial Data
Let’s be clear – nobody is claiming that Tamiflu doesn’t work. It appears to shorten bouts of flu by a day or two, but nobody can determine if it can prevent severe disease because there is insufficient data. Australian researchers analysed 20 published trials that focused on prevention, treatment and adverse reactions. The reviewers had to leave out eight trials because they had not been published. Roche offered them “under conditions we thought unacceptable, and what was offered to us was insufficient to analyse properly,” said Professor Christopher Del Mar, from Bond University in Australia. The authors say they were hampered by the “paucity of good data”. They suspect that previous evidence on the effects of Tamiflu and other drugs of this class may be unreliable. They are calling on governments to set up studies to monitor the drugs for safety. Roche says that it will put all of the data on a password protected site, but it isn’t yet clear who will have access to it.
A disturbing pattern
The Tamiflu situation isn’t an isolated case. The big pharmaceutical companies (Big Pharmas) have been widely criticized by the research community for decades because of their selective publication and use of data and results from the rigorous clinical trials that all new drugs have to undergo before they can be marketed. There have been many academic studies of the literature that all conclude that the Big Pharmas make selective use of the data and only publish material that supports their marketing efforts.
A 2006 study by researchers1 in Pakistan highlights the problems. Their report says – “We searched Medline, Embase and PsycINFO databases for this study besides hand searching BMJ from January 2003 to November 2005. We included systematic reviews, cross-sectional surveys, letters, editorials, comments or news items that referred to actual incidences of withholding, suppression, selective release or selective publication of clinical trial data by pharmaceutical companies.” They looked at over 3000 potentially relevant published articles and narrowed them to 75 that met their research criteria. They then listed systematic reviews and surveys studying the phenomenon of selective reporting before describing case studies relating to individual drugs and groups of drugs.
They found that systematic reviews demonstrated evidence of selective reporting of outcomes, but none of them looked at bias in reporting in relation to the pharmaceutical companies. Industry surveys showed that companies withhold evidence that is critical to patent applications, but, not surprisingly, nobody would admit that data was not published for other commercial reasons. They grouped the case studies into four categories that we’ll describe next. They concluded that “selective reporting of trial data has been recognized as a major problem and recent reports by the UK House of Commons Health Committee and the American Medical Association discuss this phenomenon in significant detail.”
Unreported negative results
Perhaps the most insidious manipulation of access to clinical trial data is the tendency for the Big Pharmas to selectively withhold data that might interfere with their marketing of a product. In 2002 National Institute of Clinical Excellence UK (NICE) accused drug companies of refusing to disclose the patient-level data needed to calculate cost-effectiveness of interferon beta for treating multiple sclerosis. We list other examples below.
Partial disclosure of Clinical Trial Results
Instead of reporting and interpreting the results of all clinical trials to the Food and Drug Administration (FDA) and NICE, the Big Pharmas regularly select material that supports their application and omit information that might raise questions that could result in a need for further research.
Concealment of adverse events
This can range from not conducting trials that might reveal a side effect, or conducting benign trials, to stopping trials prematurely if the results might turn out to prove damaging to the manufacturer. One analogy would be a tobacco manufacturer publishing results from an experiment to see if dropping a cigarette onto people from a height of six inches resulted in injury, but not publishing adverse results from a study of links between smoking cigarettes and cancer, then claiming that cigarettes are provably safe.
Pressure on investigators to stop publication of results
The Big Pharmas have been found guilty of bribing FDA officials to approve products that probably should not have been. There is a widespread belief that bribery and corruption is still a major problem at the FDA, where poorly paid government workers are being asked to pit their wits against the massive machinery and resources of the Big Pharmas. The latter are loaded with “Marketing and Administration” funds that they don’t have to account for in detail.
Examples of the problems
The following is a summary of typical findings in each of the above categories that the Pakistani researchers defined:
2. Two other trials which showed that venlafaxine (another similar antidepressant) was unlikely to provide clinically important improvement in depressive symptoms, but had increased risk of discontinuation because of adverse events and raised risk of suicide related events, were also unpublished.
3.. Another study found that none of the large negative trials of paroxetine and venlafaxine (two each) for treating depression in children and adolescents were ever published.
4. In June 2004 a consumer fraud lawsuit was filed against Glaxo Smith Kline (GSK) for allegedly engaging in “repeated and persistent fraud by concealing and failing to disclose to physicians certain information about Paxil (paroxetine)”. It claimed that the concealed information “impaired doctors’ ability to make the appropriate prescribing decisions for their patients and may have jeopardized public health and safety.” GSK finally settled the lawsuit US$2.5M stating that although it believed that the allegations were “unfounded” it wanted to avoid the expense of a protracted legal battle.
5. The FDA warned IRC in a letter in 1995 that, in a previous published report of a trial of Remune (an HIV-1 immunogen) sponsored by IRC, the results for two subjects had been excluded from the report even though the report stated that data for all subjects had been included, and that the statistical analysis was not the one included in the study protocol. The warning letter also accused IRC of “changing data retroactively for several reports; modifying adverse experience information; and changing data categories retrospectively, after unblinding (revealing the relationship between experiments and patients).
2. A trial evaluating Celebrex (celecoxib) was reported as a three arm trial comparing it with ibuprofen and diclofenac, for incidence of upper gastrointestinal (GI) complications and symptomatic ulcers over 6 months. The study presented a subgroup analysis on aspirin use despite the primary outcome measure being statistically non-significant. It claimed that the decrease in upper GI toxicity was strongest among patients not taking aspirin at the same time. However, the data available to the FDA showed that in patients not taking aspirin, diclofenac and celecoxib seemed to have similarly low GI toxicity compared with ibuprofen, and that patients taking ibuprofen had about the same GI risk regardless of whether or not they were also taking aspirin. The FDA found that “For upper GI safety, and also for global safety, there does not appear to be any meaningful advantage for Celebrex, “a conclusion completely opposite to the one reached by the authors of the [Big Pharma] study.”
2. In a letter to the Lancet Wilmshurst stated that Sterling Winthrop had tried to influence the results and publication of scientific trials. The specific complaints included, amongst others, discontinuation of trials when the results appeared to show its drug amrinone in an unfavourable light and failure to report adverse effects with amrinone. The Netherlands drug authorities, when refusing a license to amrinone, stated that “our assessor drew our attention to the fact that all quantitative data on peripheral blood and bone marrow had been deleted from the registration file.” Amrinone frequently causes thrombocytopenia.
3. Manufacturers Wyeth and Pfizer heavily promoted menopausal hormone drugs, despite the fact that they knew of the increased risks of breast cancer, heart attacks, stroke, blood clots in the lungs and dementia. Judges in St. Louis and Philadelphia have reached opposite conclusions on whether or not the companies have committed crimes. Meanwhile, after extensive advertising and canvassing by the Big Pharmas, the National Institutes of health have somehow decided to use the term “menopausal hormone therapy” instead of the, somewhat tainted, original term, “hormone replacement therapy.”
2. In a similar case in 1987, Dr Betty Dong of University of California at San Francisco (UCSF) was victimized by Flint Laboratories (later Boots). Her study, finished in 1990 showed that their new drug produced results that were bioequivalent to three other compounds. Over the next 4 years Boots leveled many criticisms at the study to discredit it and to prevent its publication. Dr. Dong claimed to have been twice threatened with the possibility of lawsuit should sales of Synthroid suffer as a consequence of publication. The company denied making this threat. Meanwhile, employees of Knoll/Boots published a reanalysis of Dr. Dong’s data, without acknowledging the original investigators, and reaching opposite conclusions to Dong et al. Finally, after the story had been published by the Wall Street Journal and under pressure from the FDA, Knoll agreed to let the study be published, 7 years after its completion and 3 years after its original acceptance. Several investigators of the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) dropped out of the investigative group when the final paper was in preparation. In a letter to JAMA they explained that they dropped out because they believed that the “sponsor of the study was attempting to wield undue influence on the nature of the final paper. This effort was so oppressive that we felt it inhibited academic freedom.”
What should be done?
The independent Pakistani researcher’s report commented that “We feel that the two crucial steps that would go a long way towards ending the fundamental breach of trust that underlies the practice of selective reporting of [Clinical Readiness Trial] data are:
The first goal has been realized now, the second is hopefully within our sights. Until it is achieved clinicians and researchers should continue to strive towards it.”
That was in 2006. The problem is well known, but nothing is being done about it, mainly because our politicians are in the pockets of the Big Pharmas. As we’ve seen above, we can’t be sure that any drug brought to the market has actually passed rigorous scientific scrutiny. That won’t be possible until the drug companies are legally obligated to disclose all clinical trial data.
Tomorrow, we’ll look at the reason that we pay much higher prices (up to 55% more) for our prescription drugs than people in other developed countries. There’s a clue in the preceding paragraph.
Sources:
1 “Do Pharmaceutical Companies selectively report Clinical Trial Data?” – Syed Ahmer, Imran Ijaz Haider, Duncan Anderson, Pradeep Arya – Pak J Med Sci July – September 2006 Vol. 22 No. 3 338-346.