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.
- D W Light, J Lexchin & J J Darrow (2013) Journal of Law, Medicine and Ethics 14 (3) pp590-610