122. Disclosure of the Results of Clinical Trials: Case Study of Tamiflu and Implications for Statins

One of the key issues to emerge from the recent spat between Sir Rory Collins and the BMJ about statins (1) has been the refusal of the Cholesterol Treatments Trialists’ Collaboration (CTT) at Oxford University to allow open access to the original clinical trial data. The independent panel set up by the editor of the BMJ concluded that it:

“strongly believes that the current debates on the appropriate use of statins would be

elevated and usefully informed by making available the individual patient-level data

that underpin the relevant studies” (2).

There have been suggestions that the information which is released for publication and to the regulatory bodies is not a true representation of the primary data obtained in the clinical trials (3).

Recently the original data on ‘flu vaccines have been released and it is especially pertinent to discover the insight this example provides.

Tamiflu is one of the medicines used to treat or prevent many different types of flu including bird flu and swine flu. It is recommended by the World health Organisation (WHO) and has been approved by the Food and Drugs Administration (FDA) in the US and by the European Medicines Agency (EMA). In the UK the government has spent £424m in recent years but much of this has had to be discarded because it was never used according to a critical report by the National Audit Office (4).

It is claimed that it will reduce the duration and severity of the flu but questions have been raised about the evidence on which this is based.

The House of Commons Select Committee on Science and Technology has been conducting an Inquiry into “Clinical Trials and Disclosure of Data”. In particular the inquiry focused on the need for transparency of the results of clinical trials, which are primarily concerned with the evaluation of drugs prior to approval (5).

Specific information relating to Tamiflu was presented in a submission from the Cochrane Collaboration which is an international network of volunteer scientists who carry out reviews of evidence on interventions in health care using highly structured and reproducible methods. Cochrane reviews are considered as the gold standard in evidence-based decision making for interventions and are used by many governments in the formulation of public health policies. It is independent of the pharmaceutical companies and any other potential conflicting interests. A group of their researchers had been reviewing 2 vaccines used for ‘flu, namely zanamivir (Relenza, GW now GSK) and oseltamir (Tamiflu, Roche). In their submission they explained the problems encountered in their attempts to obtain the information which was required for their evaluations. In 2009 the team was doing an update of an earlier review which had been published in 2005, when it received a query from a Japanese paediatrician. Dr Keiji Hayashi wanted to know how it was possible that in our 2005 update we had included 8 unpublished Tamiflu trials contained in extreme summary form within another review funded by Roche and carried out by Roche staff and consultants. How could we possibly have done that as we had not seen the original studies? As a consequence Roche was approached but only agreed to release the original raw data if the reviewers would sign a confidentiality clause. Obviously this was not possible because it would compromise the independence, transparency and reproducibility of the report. However as result of coverage on Channel 4 News and in the British Medical Journal Roche publicly promised full study reports. Despite only 4-5 parts of the 10 trials were handed over as Roche claimed that would all that was needed. Subsequently the documents were released and much to their surprise the researchers discovered that there is a clinical study report for each drug trial conducted. This is a complex document containing hundreds or thousands of pages of information with minute details about trials, their planning and execution. Up to that point the Cochrane reviewers were totally dependent on a journal article of a few pages.

At the outset they were aware of 26 trials but it subsequently emerged that there were 123 trials on Tamiflu. The fact that so many were kept under wraps may have had damaging effects on public and clinician confidence in the rigour of how medications are assessed in the UK for safety and effectiveness. There is also a risk that NHS funds have not been used for interventions which offer the best value for money.

  • Nevertheless the Cochrane team did succeed in gaining access to the material which Roche had submitted to the EMA as well as comments made by the FDA on Tamiflu. As a result the team was able to compare the more detailed information with relatively few publications which had been available previously. They found that there were discrepancies in reporting harms and some important aspects of study design between publications and regulatory reports. There were also suggestions that the drug interferes with the natural antibody production. If this is the case it would mean that the use of Tamiflu weakens natural host defences and may weaken response to any antigen stimulating interventions such as vaccines. The regulatory evidence released from EMA and FDA indicates that the positive effects of the drug are not as marked as those claimed by the manufacturer and its consultants in industry-sponsored publications. In agreement with the FDA there was no reliable evidence to conclude that Tamiflu is effective against influenza complications (e.g. pneumonia) and person-to-person transmission.

CONCLUSIONS

In the light of the evidence which has come to light the authors question whether the government would have agreed to stockpile Tamiflu if the complete picture was available when the decision was made. They also note that the WHO and the Centers for Disease Control (CDC) in the US apparently disregard this information and continue to recommend Tamiflu.

This particular case study is confirmation that information has been manipulated by one company in order to improve the chances of approval being granted by the regulatory authorities. There is also no doubt that this type of action is used to advantage in the market place.

Clearly this revelation has major implications for statins. It would not be in the least surprising that a similar approach is being used by the manufacturers of statins. It would certainly explain why Rory Collins and his colleagues at the CTT are so reluctant to allow any outsiders to have access to the clinical trial data which they have. There are already serious doubts about the value of statins, especially when used as a preventive measure in people who have not had problems with heart disease (6). The Department of Health and other bodies such as NICE must insist that the statin data at the CTT and elsewhere is open to scrutiny as a matter of urgency.

NOTE: It is extremely unfortunate that the Cochrane team which recently review statins did not show anything like the same determination as the one investigating Tamiflu. Had it done so it might well have reached a conclusion which was much less favourably disposed towards the use of statins (7). It is rather ironic that relied so heavily on the information provided by the CTT and apparently did not have access to the original trial data. As a consequence, the reputation of the Cochrane Collaboration has become somewhat tarnished, which is a great pity!

REFERENCES

  1. http://vernerwheelock.com/?p=528
  2. http://journals.bmj.com/site/bmj/statins/Final%20report%20of%20the%20independent%20panel%20310714.pdf
  3. http://vernerwheelock.com/?p=575
  4. http://www.nao.org.uk/report/access-to-clinical-trial-information-and-the-stockpiling-of-tamiflu-2/
  5. http://www.publications.parliament.uk/pa/cm201314/cmselect/cmsctech/104/104vw05.htm
  6. http://vernerwheelock.com/?p=432
  7. http://vernerwheelock.com/?p=545

 

 

121. Time for a Reality Check on the NHS

According to a report in The Guardian:

The NHS is generally acknowledged to be facing a growing funding crisis after four years of tight settlements, deepening demographic pressure and an inefficient system that splits health and social care. The Nuffield Trust has suggested there will be a financial shortfall of £2bn in 2015-16” (1).

The politicians are desperately trying to overcome the problems by finding more money.

The critical feature is that there is an almost total failure to conduct any kind of hard-nosed analysis to identify the fundamental issues and devise suitable objectives for the NHS. We have to face the reality that health is deteriorating as shown, for example, by the doubling of diabetes, primarily Type (T2D) in the past 15 years. The number of people who require care and nursing is growing steadily. It is therefore no surprise that the costs continue to increase. Clearly this is not sustainable in the long term. If we carry on in this way we will finish up like the USA which spends more than twice the amount on health care as other developed nations, but ranks 49th in life expectancy worldwide.

Instead of accepting that there is a need for additional funds the politicians should be trying to determine what should be done to prevent standards of public health getting worse and working out how to reverse current trends so that a steady improvement can be achieved. Conceptually this is not difficult. The current approach is primarily “curative”. Unfortunately a cure is impossible in the vast majority of cases and the best that can be done is to “manage” the condition or disease. The obvious answer therefore is to place much more emphasis on preventing the disease in the first place.

So why have we come so far down the wrong road? To understand this we have to consider the role of the drug companies. Most of us have been conditioned or “brain washed” into believing that there should be a “cure” for every possible form of ill-health we experience. Even if one is not available at present all we have to do is pour money into research and eventually the scientists will come up with a remedy. While this may work for a number of diseases (eg antibiotics and certain infections) it is definitely not the answer for all diseases. With many of them the damage is permanent. For others, a “cure” may be possible in the short term but if the primary cause (eg exposure to toxins or poor diet) is not removed then the likelihood is that disease will re-cur.

Any analysis of the current difficulties of the NHS must examine the role of the
drug companies. The expenditure on drugs by the NHS is about £14B, which is almost 10% of the total budget (2). The first point to note is that for many of the drugs being prescribed, there is no reliable evidence to demonstrate that they are effective. Quite the contrary, many of them are ineffective. One way of assessing this is to determine the NNT (Number Needed to Treat). This is the number of people who have to be treated in order that one will benefit. This may come as a surprise to many who quite naturally assume that if they have treatment with a drug it will almost certainly help them to recover. However if the NNT is 10 it mean there is a 10% chance of benefit and with an NNT of 100, then there is only a1% chance. Some examples from the NNT website, which only uses high quality studies in its analyses, are shown in Table 1(3). I believe most people would be absolutely astounded to see these results. The normal expectation is that any treatment will have a positive effect for the individual involved. This is certainly true of antibiotics so it somewhat disconcerting to learn that there is only a 1 in 4 chance that the treatment will prevent a respiratory tract infection. However for other treatments the odds of success are even smaller. With thrombolytics for a major heart attack, only 1 in 43 benefits and even then that is dependent on the treatment being applied within 6 hours. The results are even worse if treatment is delayed. Furthermore there were some risks that serious harm could also occur. Despite all the hype it turns out that the NNT team only find benefits for statin treatment in those with known heart disease but occurs in 1 patient out of 83. However the risks of developing diabetes are 1 in 50 while 1 in 10 may expect muscle damage. It seems highly likely that perceptions of the benefits of drug treatments are very much greater than the reality. It would be fascinating to discover how many people would agree to these treatments if they were informed of the chances of personal benefit beforehand. Even more astounding is the revelation that although some drugs have limited benefits for some conditions, when used for others there is no benefit whatsoever and in many cases those treated suffer adverse side-effects. This is appalling. It is quite obvious from this that the benefits of drug use have been grossly exaggerated. Hence it follows that most of the money spent by the NHS and any other body/individual on drugs is wasted. Effectively the pharmaceutical industry is sucking resources out of the system which could be spent in other ways that would facilitate patients. From a policy perspective, reducing expenditure on drugs by the NHS should be a top priority. Unfortunately there is no indication that any politician is aware of this information let alone prepared to tackle this issue head on.

TABLE 1. The Benefits and Harm Associated with Various Medical Treatments

Treatment Benefits Harm
Beta Blockers for Acute Heart Attack (Myocardial Infarction). None were helped 1 in 91 were harmed by cardiogenic shock

 

Early Invasive Management for Acute Coronary Syndromes None were helped (preventing death)

 

1 in 9 were helped by feeling less pain in chest

 

1 in 59 were helped by avoiding a heart attack in the next year

1 in 33 were harmed by suffering a heart attack.

1 in 33 were harmed by suffered major bleeding

Anti-Hypertensive Treatment for the Primary Prevention of Cardiovascular   Events In Mild Hypertension None   were helped (preventing death, stroke, heart disease, or   cardiovascular events 1 in 12   were harmed (medication side effects and stopped the   drug)
Statins Given for 5 Years   for Heart Disease Prevention (With Known Heart Disease)

 

1 in 83 were helped (life saved)

1 in 39 were helped (preventing non-fatal   heart attack)

1 in 125 were helped (preventing stroke)

1 in 50 were harmed (develop diabetes)

1 in 10 were harmed (muscle damage)

 

Statins for Acute Coronary Syndrome None   were helped (life saved; heart attack, stroke, or heart   failure prevented) An unknown number were harmed (medication side   effects/adverse reactions)
Statin Drugs Given for 5 Years for Heart Disease   Prevention (Without Known Heart Disease) None were helped (life saved)

1 in 60 were helped (preventing heart attack)

1 in 268 were helped (preventing stroke)

 

1 in 50 were harmed (develop diabetes)

1 in 10 were harmed (muscle damage)

 

Blood Pressure Medicines for Five Years to Prevent   Death, Heart Attacks, and Strokes 1 in 125 were helped (prevented death)

1 in 67 were helped (prevented stroke)

1 in 100 were helped (prevented heart attack)

 

 

1 in 10   were harmed (medication side effects, stopping the drug)
Thrombolytics Given for Major Heart Attack 1 in 43 were helped (life saved, given within   6 hours)

1 in 63 were helped (life saved, given between   6-12 hours)

1 in 200 were helped (life saved, given   between 12-24 hours)

 

1 in 143 were harmed (major bleeding episode)

1 in 250 were harmed (hemorrhagic stroke)

 

Thrombolytics   for Acute Ischemic Stroke

 

 

None   were helped (stroke symptoms improved) 1 in 20   were harmed (symptomatic intracranial hemorrhage)
Prophylactic   Antibiotics for Reducing ICU Respiratory Tract Infections and Mortality in   Adults 1 in 18 were helped (life saved)

1 in 4 were helped (prevented one respiratory   tract infection)

 

An unknown number were harmed (medication side effects/adverse   reactions)

 

Once the limitations of drugs are appreciated it follows that we have to accept that many diseases cannot be cured. Whilst some alleviation may be possible, the reality is that if these diseases are to be overcome, the only effective strategy is prevention. Essentially this means lifestyle. In this blog I will focus primarily on diet because there is now overwhelming evidence that it does play a critical in determining an individual’s personal health. This brings us up against another fundamental difficulty which is that much of the official advice is fundamentally wrong and has therefore been a crucial factor contributing to many of our common health problems.

There are convincing reasons why T2D, not obesity, should be regarded as the indicator of public health status. During 2013-2014 there were 45.1 million items prescribed for diabetes, with a net ingredient cost of £803.1million (4). This represents an increase of 66.5% in the number of items and 56.3% in the net ingredient cost since 2005-2006. In England it is estimated that 6% of the population has diabetes and the total cost is currently about £10billion (5). It is estimated that by 2025 there will be 5 million people with diabetes in England (6). Those with diabetes have a reduced life expectancy and an increased risk of retinopathy, stroke, kidney failure, heart disease and amputation of limbs.

A man diagnosed with T2D at age 40 will lose almost 12 years of life and 19 Quality Adjusted Life Years (QALYs) compared with a person without diabetes. A woman of the same age will lose about 14 years of life and 22 QALYs (7). Despite the huge expenditure on drugs, there are serious questions about the effectiveness of treatments of T2D to lower the blood glucose. In a meta-analysis of data from 13 randomized controlled trials there was no benefit, in adults with T2D, from intensive glucose lowering in terms of all-cause mortality or deaths from cardiovascular disease (8). Furthermore, an increase in all-cause mortality of 19% cannot be ruled out. Only one study showed a protective effect on myocardial infarction but this was counterbalanced by an increase in total mortality. The authors pointed out that drugs for the treatment of diabetes are being approved on the basis of their effectiveness in lowering blood glucose, despite the fact that there is no evidence based on clinically relevant criteria. It all adds up to more evidence about the misplaced confidence in the use of drugs to cure many diseases.

There is ample evidence that T2D can be controlled, possibly even cured completely by making changes to the diet (9). The condition is directly due to the increased level of glucose in the blood. As a result the pancreas has to produce insulin to prevent excess glucose in the body. Excessive insulin damages many of the organs, which can eventually lead to a range of diseases. If there is too much glucose over a prolonged period the pancreas is unable to cope and the glucose becomes rampant, causing all sorts of damage. The solution is obvious. Reduce the amount of glucose which enters the body by altering the diet. Sugar is one of the main culprits, so it should be avoided like the plague. In addition starch is broken down to produce glucose. This means that foods such as refined flour, rice or pasta should be limited because the starch is released quickly giving rise to big increases in the blood glucose.

Essentially this means a diet which is low in carbohydrates (LC). The big problem is that the official advice is to increase carbohydrates. There is a strong possibility that those diagnosed with T2D will be advised to replace fat with carbohydrates. This is fundamentally wrong! The recommendation to reduce fat and especially saturated fat (SFA) does not stand up to rigorous examination. In fact, many of the individual SFAs are important nutrients (10). So what we should be doing is limiting the carbohydrates and consuming plenty of fats

In order to make progress it is essential to alter the dietary advice. However this will not be easy. Although there is growing appreciation to limit sugar intake, the official advice from government and the NHS is to reduce fat. This means that those people who are genuinely attempting to consume a healthy diet will opt for low fat versions of dairy, meat and other types of food. Unfortunately this are usually formulated by removing the fat and replacing it with sugar and/or sweeteners. So the consumers are missing out on valuable nutrients and pushing up their intake of sugar. The official advice is to replace the fat with complex carbohydrates, such as wholemeal bread, potatoes, rice and pasta. All of these contain starch which is broken down to glucose, which inevitably raises the level of glucose in the blood. This approach is fully supported and promulgated by the vast majority of professional dietitians and nutritionists, who in any event feel compelled to comply with the official doctrine.

While recognizing the difficulties, it is the responsibility of the politicians to set the agenda and formulate policy objectives accordingly. Clearly it will mean that they have to take on very powerful vested interests, who will fight tooth and nail to maintain the status quo because they are doing very nicely. Politicians must be prepared to tackle bodies such as NICE which is “not fit for purpose” (11).

The current strategy is not working. Vast sums of public money are being wasted. Many people are suffering unnecessarily and dying prematurely. This is a huge challenge for the politicians. Are there any out there with the intellectual ability, determination and astuteness to address this issue?

 

REFERENCES

  1. http://www.theguardian.com/politics/2014/sep/22/ed-miliband-speech-tax-tobacco-nhs-labour-conference
  2. http://www.theguardian.com/society/2013/nov/06/drug-industry-nhs-cap
  3. http://www.thennt.com/
  4. Remy Boussageon et al (2011) http://www.bmj.com/content/343/bmj.d4169.pdf%2Bhtml
  5. http://www.hscic.gov.uk/catalogue/PUB14681/pres-diab-eng-200506-201314-rep.pdf
  6. http://www.diabetes.org.uk/Documents/About%20Us/Statistics/Diabetes-key-stats-guidelines-April2014.pdf
  7. http://www.diabetes.org.uk/Documents/Reports/State-of-the-Nation-2012.pdf      
  8. http://jama.jamanetwork.com/article.aspx?articleid=197439
  9. http://vernerwheelock.com/?p=422
  10. http://vernerwheelock.com/?p=153
  11. http://vernerwheelock.com/?p=569

 

 

120. Revelations about Aspartame

Aspartame is a low-calorie sweetener which is produced by G D Searle a company owned by Monsanto. It is approximately 200 times sweeter than sucrose. According to the official website the benefits include:

  • Aspartame Tastes Like Sugar
  • Aspartame Enhances and Extends Flavors
  • Aspartame Does Not Promote Tooth Decay
  • Aspartame is Helpful for Individuals with Diabetes
  • Scientific Studies Show Aspartame is Beneficial in Weight Control
  • Aspartame Can Be Part of a Healthful Diet (1).

The Food Standards Agency (FSA) takes the view that aspartame is perfectly OK as shown by this extract from the website:

Aspartame was first approved in the UK in 1982 following the review of its safety by the UK’s Committee on Toxicity, Consumer Products and the Environment (COT), a committee of independent experts that advises the Government on the safety of food chemicals. This was reaffirmed in 1988 by the European Commission’s former Scientific Committee on Food (SCF).

Following the publication of a number of anecdotal reports, which cast doubt on the safety of this sweetener, the SCF reviewed more than 500 papers published in the scientific literature between 1988 and 2001 on the safety of aspartame, including studies supporting the safety of aspartame and others pointing to potential adverse effects, which concluded, in 2002, that there was no evidence to suggest a need to revise the outcome of their earlier risk assessment or the Acceptable Daily Intake (ADI) previously established for aspartame of 40 milligrams per kilogram of body weight per day (40 mg/kg bw/day).

A study published by the Ramazzini Foundation in Bologna, Italy, in July 2005 claimed to have shown that rats given dosages of aspartame equivalent to the Acceptable Daily Intake (ADI) may develop tumours. EFSA assessed the study and raised a number of concerns regarding it. They concluded, that ‘there is no need to further review the safety of aspartame nor to revise the previously established ADI’.

The FSA supported the conclusions of EFSA’s review but reiterated that all approvals of food additives should be kept under review as and when new scientific information becomes available. Indeed, as part of its systematic re-evaluation of all food additives, EFSA has re-evaluated the safety of aspartame ………As a result, it concluded in December 2013 that ‘aspartame and its breakdown products are safe for human consumption at current levels of exposure’ ” (2).

However not everyone would agree with this position. In particular, Devra Davis has delved into the background and she would certainly dispute the rather complacent line taken by the FSA (3). Devra  has impeccable credentials. She is an epidemiologist who spent 10 years employed by the National Academy of Sciences. During her time as Senior Advisor to the Assistant Secretary for Health in the Department of Health and Human Services, she advised leading officials in the United States, United Nations, European Environment Agency, Pan American Health Organization, World Health Organization, and World Bank. Between 1983 and 1986 she served as a member of the Board of Scientific Counsellors of the U.S. National Toxicology Program. She founded the Center for Environmental Oncology of the University of Pittsburgh Cancer Institute where she was director from 2004 to 2010.

In an interview in the late 1990s, the author discovered some interesting history about aspartame from James Olney, a research neurologist and psychiatrist at Washington University in St Louis. In 1969 a study conducted by researcher Harry Waisman with 7 infant monkeys found that after drinking milk flavoured with aspartame for a year, one was dead and 5 had suffered epileptic seizures. In 1971 Waisman died and the work was never completed. However Olney’s own studies showed that aspartame paired with MSG to produce brain tumours in rats. Two years later, FDA scientist Martha Freeman decided the information submitted by the manufacturers on safety was inadequate.

In July 1976, the FDA decided to investigate the 15 key aspartame studies submitted by G D Searle and set up a Task Force under the chairmanship of Jerome Bressler. The sequence of events following the publication of the report is described in a document prepared by the Aspartame Toxicity Information Center (4). This provides a mine of information which should be consulted by anyone who is interested in the background to the approval of aspartame by the FDA. The references have been removed but many relate to official US Government documents. In August 1977, the Bressler report was released and it contained major criticisms of the procedures relating to the material presented by Searle, namely:

  • “In one study, 98 of the 196 animals died but were not autopsied until as much as one year later. Because of the delay, much of the animal tissue could not be used and at least 20 animals had to be excluded from postmortem examinations
  • The original pathology sheets and the pathology sheets submitted to the FDA showed differences for 30 animals
  • One animal was reported alive at week 88, dead from week 92 through week 104, alive at week 108, and finally dead at week 112
  • An outbreak of an infectious disease was not reported to the FDA
  • Tissue from some animals were noted to be unavailable for analysis on the pathology sheets, yet results from an analysis of this “unavailable” tissue was submitted to the FDA
  • There was evidence that the diet mix was not homogeneous allowing the animals to eat around the test substance. This evidence included a picture and statements by a lab technician
  • Fifteen foetuses from animals in one experiment were missing
  • Sections from the animals were too thick for examination
  • There was no documentation on the age or source of the test animals
  • There was no protocol until one of the studies was well underway
  • Animals were not permanently tagged to prevent mix ups
  • Some laboratory methods were changed during the study, but not documented.”

A G.D. Searle pathologist referring one of the studies was quoted by investigators as saying:

You should have seen things when this study was run — there were five studies being run at one time — things were a mess!”

Bressler himself commented:

The question you have got to ask yourself is: Because of the importance of this study, why wasn’t greater care taken? The study is highly questionable because of our findings. Why didn’t Searle, with their scientists, closely evaluate this, knowing fully well that the whole society, from the youngest to the elderly, from the sick to the unsick . . . will have access to this product.”

At this point it should be noted that Donald Rumsfeld who had just left office as Defense Secretary had been appointed as the CEO of Searle. It was evident that he had been hired early in 1977 because of his connections with government and with the Republican Party, although at that time the Democrat Jimmy Carter was president.

In September 1997, the Director of the FDA’s Bureau of Foods received a report from another Task Force which claimed that the Searle studies appeared to be authentic (meaning that they hadactually been conducted).

For each of the major discrepancies found by the Bressler-led Task Force — those listed above and many others – there was a comment in the FDA Bureau of Foods Report minimizing the problem. It seemed that no matter how serious the mistakes were, the FDA Bureau of Foods was determined toaccept the studies by G.D. Searle.

The experimental errors as described above were so bad that it proved difficult to minimize all of the major errors in these key studies. In some cases, the best that they could do was to say that “The Task Force could find no evidence that this was a deliberate attempt to influence the study.” or “It could not be determined if the results would have been altered….”

In other words it was evident that moves were being made to downplay the serious criticisms in order to pave the way for approval. This was confirmed by Jacqueline Verrett, a senior investigator at the FDA, who earlier had conducted an examination of the procedures and protocols which applied to the Searle studies. After she left the Agency, she was interviewed by a journalist who reported as follows:

Jacqueline Verrett, the senior scientist on the review team, said members were barred from stating opinions about the research quality. ‘It seemed pretty obvious that somewhere along that line they(bureau officials) were working up to a  whitewash,’ she said. ‘I seriously thought of just walking off of that task force.’ Verrett, now a private consultant, said that she and other members wanted to ‘just come out and say that this whole experiment was a disaster and should be disregarded.”

In her testimony before the U.S. Senate during 1987, Dr. Verrett stated the following:

This authentication was hence intended to verify that the submitted data had not been altered;that it reflected the actual outcome of the study and that it did not change substantially, particularly in a statistical sense, the various parameters from which the conclusion of safety had been derived.Our analysis of the data in this manner reveal that in these three studies, there were really no substantial changes that resulted, although in numerous instances, a definitive answer could not be arrived at because of the basic inadequacies and improper procedures used in the execution of these studies.

I would like to emphasize the point that we were specifically instructed not to be concerned with, or to comment upon, the overall validity of the study. This was to be done in a subsequent review, carried out at a higher level.

It would appear that the safety of aspartame and its breakdown products has still not been satisfactorily determined, since many of the flaws cited in these three studies were also present inall of the other studies submitted by Searle.

 Well, they told us in no uncertain terms that we were not to comment on the validity of it. And I hoped, although having been there at that point for 19 years, I should have known better, that there really would be an objective evaluation o this beyond the evaluation that we did. I do not feel that that was done, based on what I have read in the GAO report that I have looked at and so forth. They definitely did not objectively evaluate these studies, and I really think it should have been thrown out from day one.”

 “We were looking at a lot of little details and easy parameters in this study, when the foundationof the study, the diet and all of these other things, were worthless. We were talking about the jockey when we should have been talking about the horse, that he had weak legs. It is built on foundation of sand.”

Here are some comments about the approval process by the FDA:

  • “In March of 1979, the FDA somehow concluded that G.D.Searle’s aspartame studies could be accepted. They decide to convene the Public Board of Inquiry (PBOI).”
  • “The PBOI voted unanimously to reject the use of aspartame until additional studies on aspartame’s potential to cause brain tumours could be done. The PBOI was particularly concerned about experiment E33/34 where 320 rats received aspartame and a much higher percentage of animals in the aspartame group developed tumours than in the control group (Brannigan 1983, page 196). In addition, the PBOI was concerned about experiment E70 where 80 rats received aspartame. Both the aspartame group and the control group had an unusually high number of tumours, leading one to suspect that both groups were actually given aspartame.”
  • “On January 21, 1981, the day after Ronald Reagan takes office as U.S. President, G.D. Searle reapplied for the approval of aspartame. G.D. Searle submits several new studies along with their application. It was believed that Reagan would certainly replace Jere Goyan, the FDA Comissioner. G.D. Searle president, Donald Rumsfeld’s connections to the Republican party were also thought to play a part in Searle’s decision to reapply for aspartame’s approval on the day after Ronald Reagan was inaugurated.”
  • “In March of 1981, a 5-member panel of scientists was established by the FDA Commissioner Jere Goyan to review the issues raised by the PBOI.”
  • “In April 1981, Arthur Hull Hayes, Jr. was appointed FDA Commissioner by Ronald Reagan.”
  • “On July 18, 1981 aspartame was approved for use in dry foods by FDA Commissioner Arthur Hull Hayes, Jr. overruling the Public Board of Inquiry and ignoring the law, Section 409(c)(3) of the Food Drug and Cosmetic Act (21 U.S.C. 348), which says that a food additive should not be approved if tests are inconclusive (Federal Register 1981, Farber 1989,page 38). In an article in Common Cause Magazine, Florence Graves states that two FDA officials said that Arthur Hull Hayes, Jr. wanted to push aspartame approval through in order to signal reforms of the Reagan Administration.”
  • “On October 1, 1982 an amendment was attached to the Orphan Drug Act (an act which encourages the development of drugs for rare diseases) which modified the U.S. Patent law.
    The amendment extended the patent on only one product — aspartame — by 5 years, 10 months and 17 days.”
  • “On October 15, 1982, G.D. Searle petitioned the FDA for approval to use aspartame in soft drinks and children’s vitamins.”
  • “In 1983 acting FDA Commissioner, Mark Novitch approved aspartame for use in carbonated beverages and carbonated beverage syrupbases . FDA Commissioner, Arthur Hull Hayes was out of town the day that the approval was signed, but he worked closely with Mark Novitch on this issue. Ignoring the FDA’s own safety standards, they more than doubled the Acceptable Daily Intake (ADI) of aspartame from 20 mg/kg to 50 mg/kg.”
  • “Shortly after the FDA approval for aspartame in carbonated beverages, FDA Commissioner, Arthur Hull Hayes left the FDA under charges of improprieties, took a position as the Dean of New York Medical College and was hired as an a consultant ($1,000 per day) with G.D. Searle’s public relations firm, Burston Marsteller.”

CONCLUSION

There really is no need for much comment. The information speaks for itself. There is a lot more for anyone who wishes to follow the link to reference (4). The case for approving aspartame is built on a foundation of sand. With this background it is difficult to understand how and why the FSA and other regulatory bodies appear to be so complacent. One wonders if they have even bothered to review the information presented here. No doubt further testing has been done but how much can this be trusted in view of the appalling record of the company? If this information could be disseminated widely, then consumers could make up their own minds. As aspartame is extensively used in low calorie products, those especially at risk will be people who are attempting the follow the official dietary guidelines.

REFERENCES

  1. http://www.aspartame.org/
  2. http://www.food.gov.uk/science/additives/aspartame
  3. Devra Davis (2009) “The Secret History of the War on Cancer” pp 419-426. Basic Books New York ISBN 978-0-465-01568-9
  4. http://www.fda.gov/ohrms/dockets/dailys/03/Jan03/012203/02P-0317_emc-000202.txt

 

119. The Medical-Industrial Complex

As long ago as 1960, President Eisenhower warned about the dangers of the Military-Industrial Complex. Here is a quote from the famous speech:

“In the councils of government, we must guard against the acquisition of unwarranted influence, whether sought or unsought, by the militaryindustrial complex. The potential for the disastrous rise of misplaced power exists and will persist.

We must never let the weight of this combination endanger our liberties or democratic processes. We should take nothing for granted. Only an alert and knowledgeable citizenry can compel the proper meshing of the huge industrial and military machinery of defense with our peaceful methods and goals, so that security and liberty may prosper together” (1).

There are compelling reasons for concluding that these features are characteristic of the current relationships between the pharmaceutical industry, the medical profession and governments. In other words we now have a Medical-Industrial Complex. My thoughts have been triggered by my recent blog (2) which highlighted evidence showing that there are serious deficiencies in the regulation of drugs leading to suggestions that the process has been corrupted.

It is essential to face up to the fact that the standards of public health are deteriorating as demonstrated by the increased incidence of diabetes, which has doubled in the past 15 years. While it is true life expectancy has been extended it is highly doubtful if the quality of life has shown a corresponding improvement. The increased incidence of dementia and related conditions such as Alzheimer’s Disease means that many people are unable to care for themselves in later years. On the other hand, expenditure by the NHS in the UK continues to increase. Much of this is to meet the extra costs incurred by expenditure on the latest development in drugs and other tests/procedures.

A detailed analysis has been conducted at the Safra Institute in Harvard University entitled:

“Institutional Corruption of Pharmaceuticals and the Myth of safe and Effective Drugs” (3)

The authors contend that institutional corruption has occurred at three levels. First, large-scale lobbying and political contributions by the pharmaceu­tical industry has influenced Congress to such an extent that legis­lation has been passed which compromised the role of the Food and Drug Administration (FDA). Second, because of industry pressure, Congress has underfunded FDA enforcement capacities since 1906 so that it is incapable of thoroughly evaluating drugs submitted to it for approval. Since 1992 it has had to depend on industry-paid “user fees” which has effectively limited the FDA’s ability to protect the public from serious adverse reactions to drugs that have few offsetting advantages. Finally, industry has commer­cialized the role of physicians and undermined their position as independent, trusted advisers to patients.

Many of the drugs submitted in recent years have few if any advantages over those already on the market. In fact the FDA can actually approve drugs even if they are inferior to those which have previously approved. An evaluation conducted in France concluded that of all the new drugs approved between 1981 and 2001, about 12% offered therapeutic advantages. However between 2002 and 2011, only 8% were assessed as genuinely better than existing ones. However almost 16% were judged to be more harmful than beneficial. As few as 1.6% were considered to be substantially better. Assessments by the Canadian advisory panel to the Patented Medicine Prices Review Board and by a Dutch general practice drug bulletin have come to similar conclusions.

The reality is that most of the expenditure on research and development (R&D) is focused on developing drugs which differ slightly in chemical make-up but have a therapeutic function similar to existing drugs. This approach is adopted because it has a high chance of success and therefore less risk commercially.

Despite the failure to develop many drugs that will make a valuable contribution towards improving health, sales and profits have soared. This is because the marketing arms of the drug companies have successfully persuaded physicians to prescribe the much more costly new products that are at best therapeuti­cally equivalent to established drugs.

Two studies have found that 80% of the increase in drug expenditures was to pay for these minor-variation new drugs, rather than for important advances.  Companies claim that R&D costs are “unsustainable.” But the reality is that revenues have increased six times faster than has investment in R&D over the past 15 years.

Between 1964 and 1995, a systematic review of patients who were hospitalised in the US because of adverse drug reactions (ADR) or experienced an ADR while in hospital found some disturbing results. In all 6.8% had serious ADRs which means that 2.7 million people were affected. Of those 0.32 died, which represents 128,000 deaths every year. On this basis, ADRs are the 4th leading cause of death. These figures do not include ADRs which occurred outside hospitals.

1. Because politicians are dependent on drug companies for financial support to get elected as public representative, there has been a reluctance on their part to ensure that the regulatory process is completely thorough and effective. This can be demonstrated as follows:

  • New drugs are often tested against placebos rather than against established effec­tive treatments.
  • Surrogate or substi­tute end-points instead of the actual effects on patients’ health are often used to assess the effectiveness of new drugs.
  • Noninferiority trials which show that the product is not worse than another drug used to treat the same condition by more than a specified margin are accepted. Ideally there should be a requirement to show that the new drug is significantly better than one already on the market. These criteria do not conform to international ethical standards because they provide no useful information for prescribing.

2.  Companies are allowed to test their own products. Hence the trials are designed in such ways that they minimise the detection and reporting of harms and maximise evidence of benefits. They are permitted to exclude patients who are most likely to have ADRs, while including those most likely to experience benefit. Therefore drugs can be marketed as safer and more effective than they are in the real world.

3. In a submission to the House of Commons Health Committee, Richard Horton, editor of the Lancet, spelled out the problems which have arisen as a result of the heavy involvement of the drug companies in medical research as follows:

the extent of the commercial sponsorship of medical research and its intrusion into the academic sphere is one of the gravest threats to the independent evaluation of new medicines—indeed to the notion of an independent science base. Without greater scrutiny of the interaction between private and public sectors, the health of our population will continue to be put at risk by biased, over-interpreted, and misreported research findings. At present, our population is part of a largely unregulated experiment involving poorly investigated new medicines that have been licensed on the basis of insufficient data” (4).

He went on to describe how the entire process of publication of scientific research has been debased by the activities of the drug companies, whose over-riding consideration is the promotion of their products to the exclusion of all other factors. Examples include:

  • Manipulation of research findings. A drug which had “no effect” according to the researchers but the marketing actually claimed “primary endpoints significant in hypertensive patients”, which was a total distortion of the actual result.
  • Bias in sponsored studies: research has demonstrated clearly that sponsored studies are more likely to produce a positive result for a company than an independent study of their product.
  • Hiding negative data: the classic recent example concerned Paxil (GlaxoSmithKline). The results of trials which were not disclosed showed a pattern suggesting limited efficacy of the drug and risks of potentially fatal adverse effects. The available published evidence indicated a very different story. Under pressure, GSK was forced to reveal these hidden results—leading to a $2.5 million US legal settlement and an unequivocal FDA warning about the risks of the drug.
  • Undisclosed conflicts of interest: the escalating problem of industry payments to scientists—stock options, consultancy fees, research grants, staff costs, entertainment, conference fees, hospitality—has been recognised for several years.
  • Editorial kick-backs: The Lancet has been offered substantial sums of money in exchange for publishing certain research studies.

This is all sordid, unethical and totally unacceptable. A Medical-Industrial Complex definitely does exist. There is absolutely no doubt that industry, governments and the professionals interact and collaborate to exploit people when they are most vulnerable. Because all the players are very powerful, it will not be easy to achieve reform in order to ensure that the drug companies are subject to stringent regulatory control. Probably the best hope is transparency with the assistance of the internet. The recent incident involving Rory Collins and the BMJ is at least an encouraging sign that the drug companies and their acolytes are no longer getting their own way (5,6). The one thing we can all do is to be very, very careful before agreeing to take any drug.

REFERENCES

  1. http://coursesa.matrix.msu.edu/~hst306/documents/indust.html
  2. http://vernerwheelock.com/?p=575
  3. D W Light, J Lexchin & J J Darrow (2013) Journal of Law, Medicine and Ethics 14 (3) pp590-610
  4. http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/42/4121604.htm
  5. http://vernerwheelock.com/?p=432
  6. http://vernerwheelock.com/?p=528

 

118. Crony Capitalism. The Pharmaceutical Industry.

The use of drugs is an integral component of the conventional approach to modern medicine. Invariably a visit to your GP results in a prescription for at least one pill or potion. A similar treatment is often associated with a stay in hospital. The fundamental principle which underpins this strategy is that these medicines will be beneficial to the patient’s health. Furthermore while it is accepted that there may be side-effects, these can be tolerated if the benefits are genuinely worthwhile. The entire basis of the approach is dependent on regulatory processes that are rigorous in their assessments of the effects the drugs have on people who are treated.

Unfortunately a huge amount of evidence has emerged in recent years, which shows that there are serious deficiencies in the regulation of drugs and there are even suggestions that the process has been corrupted.

A recent book published in the US entitled “Crony Capitalism in America 2008-2012” (1) has a whole chapter devoted to the relationship between the pharmaceutical industry and the Food and drugs Administration (FDA). This has been reproduced on the Alliance for Natural Health website (2). This blog will focus on some of the key points. Although the book refers to the US many of the companies operate in the UK and it would not be in the least surprising if the relationship between the companies and the UK/EU regulatory authorities is essentially the same. Here are some of the hard realities of this business:

  1. Drug companies do not usually use natural compounds because it is impossible to patent them. As it costs somewhere around $billion to obtain approval, patenting is essential in order to recoup the costs involved.
  2. To facilitate approval process, the companies regularly hire staff with experience of working for the FDA. Many of the experts in the field who may be employed by universities and research organisations act as both advisers to the FDA and consultants to the industry.
  3. This engenders a cosy relationship between the both sides who participate in the regulation of the drugs
  4. According to a quote from the “Economist”:

Pharmaceutical companies bury clinical trials which show bad results for a drug and publish only those that show a benefit. The trials are often run on small numbers of unrepresentative patients, and the statistical analyses are massaged to give as rosy a picture as possible. Entire clinical trials are run not as trials at all, but as under-the-counter advertising campaigns designed to persuade doctors to prescribe a company’s drug.”

The “Economist” continues:

“Medical journals frequently fail to perform basic checks on the papers they print, so all sorts of sharp practice goes uncorrected. Many published studies are not written by the academics whose names they bear, but by commercial ghostwriters paid by drug firms. Doctors are bombarded with advertising encouraging them to prescribe certain drugs.”

5.       Knowledge of what is happening with respect to the progress of individual applications for approval can have major financial implications. An FDA chemist charged with criminal offences has pleaded guilty to leaking information about drug approvals or company mergers. Over a 5-year period the chemist had been involved with 25 companies and benefited to the tune of almost $4 million dollars.

6.       Once a drug has been approved it may be prescribed on a large scale, especially by official bodies such as the US government’s Medicare. Annual treatment costs for these approved drugs may be as high as $500,000 per patient. On the other hand, drugs which have not been approved are effectively banned in the US and doctors who prescribe them risk being stuck off and may even be prosecuted

7.       Although there may be compelling anecdotal evidence, including numerous case studies which indicate that naturally-occurring substances can be used successfully to treat a variety of diseases and conditions, the FDA insists that they can only be approved if the complete testing programme is implemented. Since there is no organization or company prepared to spend the money needed, there is no way that these substances will ever be approved. The position is re-inforced by the stance of the American Medical Association (AMA) which as a general rule is opposed to the use Complementary therapy but is also dependent on the pharmaceutical industry for much of its funding

8.       The use of generic drugs ought to be an effective means of reducing the costs of many drugs but this approach is to some extent stymied because the FDA insists that bioequivalence is demonstrated which adds to the costs. More significantly the FDA has a huge backlog of about 1900 applications for generics and the average time for a decision on approval is 26 months,

9.       In the US the government is very careful to avoid charging any leading pharmaceutical company with criminal misconduct. This is because conviction under the current law would mean that the government would no longer be able to purchase any products from that company. The government is too closely integrated with the drug/vaccine industry to allow that to happen. Thus, when Merck was found to have misled about its painkiller Vioxx, alleged to have caused at least 55,000 deaths (some estimates are much higher), the settlement with plaintiffs reached $4.9 billion. But Merck continued partnering with and selling to government without any interruption or even question.

This is just one example of crony capitalism in which government and industry become so interdependent on each other that there is really no effective control and the only beneficiaries are those individuals who have their “snout in the trough”. In essence the normal rules of competition are suspended and inefficiencies are rampant. It is of course the ordinary citizens who suffer because it is their taxes which are used to fund these excesses. They also miss out from the continued improvement in the quality of products coupled with a steady reduction in prices. As an example, compare the pharmaceutical industry with the mobile phone industry which advances in leaps and bounds. By contrast there is reliable evidence that there are very few new drugs which actually perform significantly better than those already on the market and some which are worse, but no doubt are promoted as “wonderful”.

REFERENCES

  1. Hunter Lewis (2013) “Crony Capitalism in America 2008-2012” ISBN 978-09887627-2-7
  2. http://www.anh-usa.org/big-pharma-and-fda-a-marriage-not-made-in-heaven/

 

 

117. Statins: Email to Julian Smith MP

Good Morning Julian,

I have just posted this article on my blog at

http://vernerwheelock.com/?p=569   More details of the damaging effects of statins will be found at http://www.spacedoc.com/statin_side_effects

My primary concern is the fact that such a large number of perfectly healthy people are suffering serious ill-health even though NICE accepts that it will not improve their health in any way. I contend that this is totally unjustified and unacceptable.

The reality is that 100s of thousands (maybe even millions) of people are being damaged by statins when the vast majority  of them do not benefit in any way. There is no doubt that there is manipulation of the results conducted by the drug companies to play up the advantages and play down the undesirable side-effects of statins. (See http://vernerwheelock.com/?p=545  and http://vernerwheelock.com/?p=528)

This issue has all the hallmarks of other scandals which have come to light recently such as Rotherham, Stafford Hospital or Hillsborough. The only difference is that much larger numbers of people are involved. There is no doubt that NICE is a major part of the problem. I believe that for a start some of the parliamentary committees should conduct a detailed investigation into the role of NICE and its relationship with the drug companies. This email is a formal request to you to place this information with the Parliamentary Committees for Public Accounts, Science and Technology and Health in the hope that they will take appropriate action. Please take any other measure you think would be effective.

All the factual information is based on thoroughly reliable sources and I believe that this issue must be addressed sooner rather than later. Let us hope that this will not be another scandal that drags on and on for years because nobody in a position to act would listen !!!

A copy of this email is being sent to the Craven Herald and I will also be placing the information on my blog at http://vernerwheelock.com/

I look forward to hearing your response.

Very Best Wishes

Verner

 

116. Microchip to beat Obesity

According to The Guardian (8september 2014) Professor Sir Stephen Bloom is developing an “intelligent microchip” which will send signals to the brain that will stop the urge to eat. Bloom is head of the diabetes, endocrinology and metabolism at Imperial College London in Hammersmith Hospital. He believes that this will reduce appetite and therefore act as a means of overcoming obesity. In the interview Bloom says that obesity increases blood pressure and therefore increases the risk of having a stroke. He mentions that higher cholesterol means a person is more likely to have a heart attack, presumably also linked to obesity. Furthermore the incidence of Alzheimer’s Disease is one third higher in people who are obese. He goes on to state that most diabetes is caused by people being slightly overweight. So he concludes that if:

“….you could get rid of obesity, diabetes would fall to about a third or maybe a quarter”.

In my opinion Professor Bloom has made a number of assumptions in developing his strategy, which do not stand up to rigorous examination. As a consequence it is extremely doubtful if he can achieve his objectives.

First of all, if we consider those who are “overweight” as determined by BMI, we find that they actually have a greater life expectancy than those with a “normal” BMI, which is regarded as the ideal    (Table 1) (1). Although there is a small increase in the number of deaths due to kidney diseases and diabetes, this is more than offset by the reductions in deaths attributed to other causes.While it is true that those who are in the “obese” category have higher death rates, this only applies to those who are severely obese with a BMI >35 (2). Even then it is crucial to recognise this does not allow us to conclude that the cause is the excess weight.

TABLE 1 RELATIONSHIP BETWEEN BMI AND EXCESS DEATHS (1000s)

                                                                 BMI
Cause of death <18.5 18.5-25 25-30 >30
Coronary heart disease +3 0 -12 +6
Other   cardiovascular +8 0 -5 +36
Lung   cancer 0 0 -10 -7
Obesity   related cancer 0 0 -3 +20
All   other cancers +3 0 +3 +2
Diabetes/kidney   disease 0 0 +15 +34
Chronic   respiratory +16 0 -30 -6
Acute   respiratory/infectious +8 0 -8 -3
Injury +2 0 -32 -13
Other   causes +6 0 -52 +13
ALL +46 0 -134 +82

 

The nutrition literature is littered with examples of confusing cause and effect, which can be simply illustrated by this example. In an area of high crime it is likely that there will be frequent observations of police cars, while low crime localities will rarely have a visit from a police car. This does not mean that the police cars are the cause of the crime rate and it certainly does not follow that crime will be reduced if police cars are kept away!

We really do need to be much more critical in our thinking. It could well be that diabetes is one cause of obesity. However the most likely explanation is that there is a common cause for both. Our main concern is diabetes Type2 (T2D). This is raised blood glucose which stimulates the production of insulin by the pancreas. The insulin directs the glucose to the liver where it is converted into fat and then stored, which can ultimately result in obesity. The high levels of insulin in the body damage many of the organs, which can lead to heart disease and cancers. The obvious answer is to reduce the amount of glucose coming into the blood by cutting back on the consumption of sugar and refined carbohydrates.

There is a growing volume of evidence that this approach can overcome T2D (3,4,5). Invariably those who successfully reduce their blood glucose also find that they lose weight and the risk factors for heart disease are also lowered.

By contrast, the results for those who focus on weight loss alone are not encouraging. For example, in the Honolulu Heart Study, 6537 Japanese-American men aged 45 to 68 in 1965 and living in Hawaii, were monitored from 1973 to 1988 during which time there were 1217 deaths. The results are shown in Table 2. It is quite clear that there has been a notable increase in the death rate of those who lost weight. On the other hand, those who gained up to 4.5kg had a reduced death rate while those who gained more than that did not experience any increase in mortality rate when compared with those whose weight did not vary (6). Similar results have been observed in other investigations (7).

TABLE 2 RELATIVE DEATHS AND CHANGE IN BODY WEIGHT

  ALL-CAUSE MORTALITY  RELATIVE   RISK
Weight loss >4.5 kg 1.21
Weight loss 2.6-4.5 kg 1.29
No change 1.00
Weight gain 2.5-4.5 kg 0.83
Weight gain >4.5 kg 0.99

 

The hard reality is that T2D is not confined to those who are overweight or obese. A recent study conducted in the USA compared the death rates between those with T2D who were normal weight (BMI 18.5-25) and those who were overweight and obese (BMI>25). It was found that the death rates for those with normal weight was more than double that of those who were in the heavier categories (8). This paper also noted that overweight and obese patients with end-stage renal disease have better health outcomes than those who are lean. Furthermore, lean people with raised blood pressure and those with heart failure have worse health outcomes than their heavier counterparts.

So any strategy which focuses on weight loss per se is unlikely to be effective and may well do more harm than good. In addition, many diabetics are not overweight so weight loss is clearly not the solution.

CONCLUSION

It is virtually certain that this project is doomed to failure. There is ample evidence to demonstrate that weight loss by calorie control is very difficult to achieve and even when successful is rarely maintained. Even then, the chances are that there will not be any benefit to health. The real danger is that it diverts attention from the methods that are effective, especially making changes to food consumption patterns by limiting sugar and refined carbohydrates.

REFERENCES

  1. http://jama.jamanetwork.com/article.aspx?articleid=209359
  2. http://vernerwheelock.com/?p=132
  3. http://vernerwheelock.com/?p=226
  4. http://vernerwheelock.com/?p=405
  5. http://vernerwheelock.com/?p=422
  6. http://www.nejm.org/doi/full/10.1056/NEJM199509143331102
  7. http://vernerwheelock.com/?p=221
  8. http://jama.jamanetwork.com/article.aspx?articleid=1309174

 

 

 

 

 

115.Statins: Another Scandal in the Making

The latest edict from the National Institute for Clinical and Health Excellence (NICE) means that virtually everyone over 50 will be recommended to go on statins. NICE recognises that 77 people will have to be treated with these drugs over a 3-year period for one person to derive any benefit (1). It is crucial to understand that most of these are individuals who are perfectly healthy: the rationale for extending the scope of those being treated is prevention rather than cure. NICE also rejects claims that there are adverse side-effects when statins are used.

It really is unbelievable that NICE should be taking this stance when the benefits are so absolutely minimal. The organisation must be living in cloud cuckoo land if it considers this decision to be reasonable and logical. If people were informed there was only one chance in 77 that they would benefit I have no doubt that that the vast majority would not agree to the treatment and that is before any consideration of side-effects. In answer to a question, a spokesman justified statin use on the grounds that with blood pressure lowering drugs, only one in 104 would benefit!

A much more realistic picture was painted by a group of medical professionals led by Sir Richard Thompson, President of the Royal College of Physicians and Dr Clare Gerada, a former chair of the Royal College of GPs (2). In a letter to NICE, copied to Jeremy Hunt, they pointed out that:

  • There is  a lack of reliable evidence to demonstrate that when statins are used for primary prevention( ie. for people who have not had heart disease) there is any reduction in all-cause mortality
  • There is sound evidence that statins do cause adverse side-effects, which include muscle pain, cognitive impairment and erectile dysfunction. A study conducted in the USA with over 150,000 middle-aged women found that those on statins had a 48% increased risk of developing diabetes compared with those on a placebo
  • As 8 out of the 12 members of the NICE committee which made the recommendation on statins have financial links with the pharmaceutical companies producing the statins, there are genuine concerns about conflicts of interest
  • In a recent survey of 511 GPs conducted by the magazine Pulse, it was found that 57% oppose the plan to lower the current 10-year risk threshold for primary prevention from 20% to 10. Only 25% would support the proposals. It was also highly significant that 55% would not personally take a statin or recommend a family member to do so, based on a 10% risk.

An analysis of the results of trials to evaluate statins, shows that most of these studies have been conducted on men. Although there are fundamental differences between men and women in the way they respond to drugs, there is no convincing evidence that statins have any beneficial effect in women.

There is evidence that pressure has been applied by drug company interests to influence the results of a Cochrane Collaboration report in order to favour the use of statins (3).

It is clear that there is a very convincing prime face case that NICE is “not fit for purpose”. In particular, there is genuine concern that it is dominated by the interests of the pharmaceutical industry. Hence drugs are being recommended which have minimal benefit and therefore public money is being wasted on drugs that are ineffective. Even worse, some patients experience side effects which are not only unpleasant but can also cause serious damage to their health.

All the indications are that this is a major scandal which ought to be tackled sooner rather than later. Recent issues including Stafford Hospital, Hillsborough and Rotherham demonstrate the inertia of the authorities to take action despite numerous warning signs. There is not the slightest doubt that there is a pressing need to examine the role of NICE and its relationship with the drug industry simply because of the evidence that I have cited here. Ideally the Ministerial team at the Department of Health should act but they are probably incapable of dealing with the modern day Sir Humphreys. However these issues could well be tackled by Parliamentary Committees, which have the power to summon witnesses and cross-examine them. I would envisage that these topics would be ideal for the Public Accounts Committee, the Health Committee and the Science and Technology Committee. It would be fascinating to watch any attempt to justify the use of stains when the number to benefit is so small. Up to now these committees have been quick to jump into action once an issue has hit the headlines. However it would certainly be preferable if they did not have to wait to be prompted from outside sources.

Recently the Parliamentary Committee on Science and Technology expressed concern about the lack of transparency of the detailed results of clinical trials conducted by pharmaceutical companies to determine the effectiveness of drugs (4). In the absence of all the available original data it is not possible to make an accurate assessment of the effectiveness of any particular drug. The full implications of this have been spelled out in a recent book by Peter Gøtzsche (5). In this he describes how Pfizer had been fined $2.3 billion in the United States for promoting off label use of four drugs, while Merck had been responsible for the deaths of thousands of patients with its deceptive behaviour around a drug for arthritis.

I will be making this information available to the various Committees in the hope that this issue will be placed on their agendas. I also intend to forward this to my MP with a request that he presses for action and I hope that other readers in the UK will also pass on to their own MP.

At the very least I would expect that all information on the odds of success and the risks of adverse side-effects should be accessible to each and every patient before agreeing to treatment with any drug. If this episode is anything to go by, I suspect that most people would be very surprised at what they learn!

REFERENCES

  1. http://www.bmj.com/content/349/bmj.g4694
  2. http://www.nice.org.uk/media/877/AC/NICE_statin_letter.pdf
  3. http://vernerwheelock.com/?p=545
  4. http://www.publications.parliament.uk/pa/cm201213/cmselect/cmsctech/writev/clinicaltrials/clinicaltrials.pdf
  5. Peter Gøtzsche(2013). “Deadly Medicines and Organised Crime: How Big Pharma Has Corrupted Healthcare Radcliffe Publishing London

114. Potential Breakthrough in South Africa

There is now overwhelming evidence that the decision to advise consumers to reduce the amount of fat and saturated fat (SFA) in the diet has turned out to be one of the most disastrous mistakes in the history of public health policy. As people implemented the recommendations it was inevitable that there was a corresponding increase in the intake of sugar and carbohydrates. This was driven by the promotion of “low fat” products, many of which were formulated by replacing the fat with sugar. In addition, there has been a phenomenal growth in the sales of soft drinks, which usually have a very high content of sugar. The changes in food consumption patterns have been accompanied by increases in the incidence of obesity, although this has tailed off a bit recently in the UK. Even more seriously, diabetes is now a major problem. Here in the UK the incidence has doubled in the past 15 years and it is expected to continue increasing. Diabetes is especially worrying because it is associate with increased risk of heart disease, cancer and Alzheimer’s Disease. The NHS in England currently spends almost £1Billion on drugs to treat diabetics, while the cost of all treatment is about £10 Billion. It is reaching the point where it is becoming unsustainable.

The solution is blindingly obvious. The cause has to be removed. Diabetes is caused by excessive levels of glucose in the blood. If the amount of sugar and starch, which is broken down to glucose, is restricted in the diet then it follows that there will be less available for absorption from the gut into the blood. The logic is irrefutable. This is fully supported by reliable scientific research and a huge number of personal case histories from individuals who have reduced their intake of sugar and refined carbohydrates. It should also be appreciated that most of this can be replaced by fats, especially the SFAs, which are valuable nutrients in their own right (1). For more details of current thinking on nutrition I can recommend “the Diet Delusion” (2) by Gary Taubes and “Big Fat Surprise” by Nina Teicholz (3).

The big hurdle is that the majority of those in the medical and public health professions are not prepared to accept this relatively “new” understanding and interpretation. The fundamental issue is that most of those in a position to initiate a U-turn have been active proponents of the existing policies which have failed so miserably. There are probably several reasons for this.

  • They have closed minds and simply cannot adjust their thinking. As a result they perform all sorts of contortions in rather pathetic attempts to justify the status quo
  • They choose to ignore the new information and the consequences
  • They just cannot face up to the fact that they have been wrong in the past and therefore presented patients and governments with advice that was faulty.

There are also very powerful business interests, including food, pharmaceuticals and weight loss which would be adversely affected if there was a big shift in policy.

At present there is little doubt that the reactionary forces hold the upper hand simply because virtually all politicians are not prepared to challenge the relevant “experts”. This may seem bizarre but it does appear they lack the ability and the confidence to do so.

However the hard reality is that we are largely dependent on the politicians to initiate action. This is why we need to watch developments in South Africa very carefully indeed.

The story starts with Professor Tim Noakes, Professor of Sports Medicine at the University of Cape Town (UCT). For most of his life he had followed the conventional dietary guidelines. He was also very active as he went running most days and had competed in over 70 marathons and ultramarathons. About 4 years ago he started to question the rationale behind the dietary he was following and promulgating to others. As a consequence he decided that the advice was fundamentally flawed and so he went through the painful process of changing his mind. His current position is explained in an interview (4). He explains the rationale in a lecture given in 2012 (5).

Within the last few weeks Tim Noakes was invited to address members of the South African Parliament , where he obviously made a significant impact(6). As a result there is already an initiative to implement some of the proposals suggested. This really is a very big step forward and it is to be hoped that sooner rather than later, there will be moves to re-formulate the public health policies in order to alter the national patterns of food consumption.

However it will not be plain sailing because there has been a backlash from other academics in UCT, who wrote a letter which condemning the stance taken by Noakes. It was signed by Prof Wim de Villiers Dean of Faculty of Health Sciences, Prof Bongani Mayosi, Head of Department of Medicine, and emeritus professor, cardiologist Dr Lionel Opie, and Dr Marjanne Senekal, associate professor and Head of Division of Human Nutrition.

Here is the letter in full:

“The apparent endorsement by Members of Parliament of South Africa of the latest fashionable diet, ‘Banting’ (‘SA’s Ticking Time-bomb’, Cape Times, 19 August 2014) and the message it sends out to the public about healthy eating, is cause for deep concern – not only regarding Parliament’s support for it as an evidenced-based ‘diet revolution’, but sadly, the long-term impact this may have on the health of the very people they have been elected to serve.

“Any diet for weight loss and maintenance should be safe and promote health in the long-term. Currently the long term safety and health benefits of low carbohydrate, high fat diets – such as Atkins, Paleo and South Beach, and in which Banting falls – are unproven, and in particular whether it is safe in pregnancy and childhood.

“Importantly, while the consumption of a low carbohydrate, high fat diet may lead to initial weight loss and associated health benefits – as indeed would a balanced weight loss diet – there is good reason for concern that this diet may rather result in nutritional deficiencies, increased risk for heart disease, diabetes mellitus, kidney problems, constipation, certain cancers and excessive iron stores in some individuals in the long term. Research leaves no doubt that healthy balanced eating is very important in reducing disease risk (see web page below dedicated to this debate).

“It is therefore a serious concern that Professor Timothy Noakes, a colleague respected for his research in sports science, is aggressively promoting this diet as a ‘revolution’, making outrageous unproven claims about disease prevention, and maligning the integrity and credibility of peers who criticise his diet for being evidence-deficient and not conforming to the tenets of good and responsible science. This goes against the University of Cape Town’s commitment to academic freedom as the prerequisite to fostering responsible and respectful intellectual debate and free enquiry.

” This is not the forum to debate details of diets, but to draw attention to the need for us to be pragmatic. Research in this field has proven time and again that the quest for lean and healthy bodies cannot be a quick-fix , ‘one- size-fits-all’ solution. The major challenge lies in establishing sustainable and healthy dietary and physical activity patterns to promote long term weight maintenance and health after weight loss, and includes addressing psychosocial, environmental and physiological factors.

“Our bodies need a range of nutrients sourced from a variety of food groups to survive. Diets like the Banting are, however, typically ‘one dimensional’ in focus. They promote increased intake of protein and fat containing foods at the expense of healthy carbohydrate containing foods, and focus on adherence to a limited food plan. Ignored are the other important factors impacting on health – like physical activity (the important of which we cannot emphasise enough), environmental factors, and individual health profiles.

“UCT’s Faculty of Health Sciences, a leading research institution in Africa, has a reputation for research excellence to uphold. Above all, our research must be socially responsible. We have therefore taken the unusual step of distancing ourselves from the proponents of this diet. To foster informed engagement of the issues related to the Diet debate, the Faculty has established a (page on its website) with material on this.”

And this is the reply:

For whatever reasons, the Faculty of Health Sciences of the University of Cape Town manages consistently to misrepresent my public message which is simply the following: a high carbohydrate diet is detrimental to the health of persons with insulin resistance whereas carbohydrate restriction in this group can be profoundly beneficial as it can reverse obesity and in some cases Type 2 diabetes mellitus, the two conditions that will ultimately bankrupt South African medical services unless we take appropriate preventive actions. This message first presented publicly in my book Challenging Beliefs in 2011, has never changed.

“It is also the message I presented to members of staff at Parliament a week ago.

“If that message is without scientific support, then the Faculty of Health Sciences has every right to cross the civil divide as it has now chosen; an action which, I suspect, is unprecedented in the history of the Faculty of Health Sciences and perhaps the history of the University of Cape Town. But if there is evidence for my position, then the Faculty is guilty of failing fully to inform its past and present science, medical and dietetics graduates in a manner appropriate for a Faculty that considers itself to be a world-leader.

” An outline of the scientific evidence for my position is presented in about 20 000 words in our book Real Meal Revolution. That work includes references to the most important scientific works (of an abundant literature) supporting my interpretation. For the Faculty of Health Sciences of the University of Cape Town consistently to deny that peer-reviewed evidence is a classic example of cognitive dissonance.”

CONCLUSION

In my opinion, the letter from the academics is totally unacceptable. To claim that that the ideas advocated by Noakes may:

“result in nutritional deficiencies, increased risk for heart disease, diabetes mellitus, kidney problems, constipation, certain cancers”

simply beggars belief. There is not a shred of evidence to support the statement. Similarly it is totally unjustified to accuse Noakes of

“outrageous unproven claims about disease prevention”.

If the authors of the report had bothered to examine the evidence, there is plenty. Wild unsubstantiated statements are the hallmarks of desperation.

There is a very little doubt that obesity, diabetes and related diseases have been caused by precisely the type of diet which the UCT academics support. The writers of the letter appear to be so committed to theories which have been totally discredited that are not prepared to consider any alternative. The fact is that they are advocating strategies which have been largely responsible for the current disaster in public health. They would do well to note the conclusion of Albert Einstein who defined insanity as doing the same thing over and over again and expecting a different result!

It is to be hoped that the South African politicians stick to their guns and adopt the Noakes approach to construct a completely new public health policy. This would undoubtedly produce enormous benefits for the country with huge improvements in the health of the population, which must pay off in the economy. There would also be savings in health expenditure.

Finally South Africa would establish itself as the world leader in health policy innovation, which ought to trigger similar initiatives in many other countries.

REFERENCES

  1. http://vernerwheelock.com/?p=155
  2. Gary Taubes (2007) “The Diet Delusion” Vermillion: London
  3. Nina Teicholz (2014) “The Big Fat Surprise: Why Butter, Meat and Cheese Belong in a Healthy Diet” Simon & Shuster New York
  4. http://www.biznews.com/health-biznews-com/2014/07/tim-noakes-makes-real-meal-critics-say-diet-dangerous/
  5. https://www.youtube.com/watch?v=5IYVIdztWWs#t=31
  6. http://www.iol.co.za/news/politics/sa-s-ticking-time-bomb-1.1737511

 

 

113. Can We Trust the Drug Companies?

The banking industry quite rightly suffers from public opprobrium because of its role in the financial crisis, manipulation of the bank rate and mis-selling of various products. By contrast the pharmaceutical industry is somewhat more highly regarded. Nevertheless recent examples of unethical behaviour indicate that the approach to business in this sector does not exactly embrace the highest principles of corporate social responsibility.

I have just discovered a website which provides reliable evidence on how this industry operates (1). In this blog I will refer to a number of issues which have arisen in recent years.

  • In an undercover investigation, initiated by a tip-off from a whistleblower, The Daily Telegraph discovered that pharmaceutical firms appear to have rigged the market in so-called “specials”. These are prescription drugs that are largely not covered by national NHS price regulations. Secret recordings by Telegraph reporters showed that sales representatives for drug firms offered to provide apparently falsified invoices allowing chemists to bill the NHS for sums far greater than they would spend. Hence the retailers would be able to send inflated invoices to the NHS, allowing them to pocket the difference. As a consequence it was estimated that hundreds of millions of pounds of public money has probably been wasted in recent years due to the practice (2).
  • In a Newsweek investigation, reporter Sharon Begley concludes that the framework of medical research is fundamentally flawed so that the wrong answers are being produced time and time again (3). According to John Ioannidis, who is in charge of the Prevention Research Center at Stanford University people are being hurt and dying because of false medical claims which are based faulty research.
  • In a recent blog I have described in detail how pressure was applied to the respected Cochrane Collaboration to influence the conclusions of an evaluation of statins (4). Two professors from the University of Oxford persuaded the compilers of the report to reach a conclusion favourable to statins, based on data produced by pharmaceutical companies, which was not open to independent scrutiny. Other evaluations have concluded that there is no net benefit from statins when used for primary prevention. Despite this NICE has made recommendations which effectively mean that everyone over 50 will be offered statins. Even NICE accepts that 77 people will have to treated in order that one will benefit! In the USA alone the expenditure on statins is more than $20 billion per year, much of which is probably unnecessary.
  • There are many examples of “breakthroughs” which turn out to worthless when subjected to further examination. Various studies which concluded that popular antidepressants work by altering brain chemistry have now been contradicted. A study done in 1996 which concluded that estrogen therapy reduces older women’s risk of Alzheimer’s was overturned in 2004.
  • Richard Smith, a former editor of the British Medical Journal (BMJ) is convinced that fraudulent research regularly appears in the 30,000 scientific journals currently published throughout the world. Furthermore even when fabricated or falsified research is discovered, journals rarely publish a retraction. Dr Smith is critical of the failure of scientific institutions, including universities, to discipline dodgy researchers even when alerted to problems by journals. Most cases are not publicised. Few countries have measures in place to ensure research is carried out ethically. In practice such incidents are simply not recognised, covered up altogether or the guilty researcher is urged to retrain, move to another institution or retire from research (5).
  • Ben Goldacre trained as a medical doctor and is the author of the “Bad Science” column in The Guardian. In his book “Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients,” he describes how he ended up prescribing the antidepressant reboxetine to his patients based on insufficient data. Despite the fact that there is overwhelming research which shows that the drug is ineffective, it was still approved in the U.K. In order to get approval of the drug in Europe, the manufacturer had simply kept quiet about its negative data. Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had shown a positive result, and that one was published in an academic journal, for doctors and researchers to read. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. Goldacre had no idea they existed. It got worse. The trials comparing reboxetine against other drugs showed exactly the same picture: three small studies, 507 patients in total, showed that reboxetine was just as good as any other drug. They were all published. But 1,657 patients’ worth of data was left unpublished, and this showed that patients on reboxetine did worse than those on other drugs. He goes on to describe how drug companies hide data about medication risks that affect children, how they attempt to intimidate the employers of researchers who produce results they don’t like, and how they routinely withhold safety data in various other ways that do harm to patients (5).The fundamental problem is that the regulatory bodies, which we would reasonably expect to stamp out such practices have failed us. Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. There is good evidence to demonstrate that the results of research funded by drug companies are highly likely to favour the manufacturer. On the other hand if the results are not favourable then there is absolutely no obligation to make these public. Consequently doctors and patients, only ever see a distorted picture of true effects of any particular drug. In view of the fact that the drug companies are the main source of information to the medical profession this is the picture which becomes widely disseminated. This is reinforced by the fact that the same messages are promulgated through the scientific journals. Although these are usually regarded as objective the reality is that are often covertly planned and written by people who work directly for the companies, without disclosure. Sometimes whole academic journals are owned outright by a single drug company (6).

REFERENCES

  1. http://www.wanttoknow.info/pharmaceuticalcorruptionmediaarticles-0-20
  2. http://www.telegraph.co.uk/health/healthnews/10133557/Pharmaceutical-scandal
  3. http://www.thedailybeast.com/newsweek/2011/01/23/why-almost-everything-you-hear-about-medicine-is-wrong.html
  4. http://vernerwheelock.com/?p=545
  5. http://www.theguardian.com/society/2006/may/03/health.medicineandhealth
  6. http://healthland.time.com/2012/09/24/a-doctors-dilemma-when-crucial-new-drug-data-is-hidden/