Drug companies, are they angels or demons?
Research with any involvement from the pharmaceutical industry is often met with a heavy dose of scepticism. Professor Peter Weissberg, our recently retired Medical Director, considers the issue.
There are some simple facts about drug development that need to be understood. It is the drug industry that has produced nearly all of the life-saving and life-changing medicines — vaccines, antibiotics, anti-cancer drugs, statins, pain killers, anaesthetics etc. that we all benefit from today.
Although many of the ideas for new drugs may have come from academic researchers funded by the likes of the BHF or Cancer Research UK, in the end, it is drug companies that turn these crucial ideas into the tablets we all take.
The cost of medicine
The main reason for this is that it costs a prodigious amount of money to take a drug successfully to market, recently estimated at $2.6 billion. This is partly because most potential new drugs fail for a variety of reasons at a late stage of their development and after millions have already been spent. Only industry has the resources to meet these costs.
And because the costs of success are so high, not surprisingly, the companies will try to maximise the return on their investment when the drug is eventually approved, but they have a limited time in which to do it. Each new drug has a limited patent life — usually 20 years — during which a company has sole rights to produce and sell it.
The window of profitability
But the clock starts ticking as soon as a patent is taken out and it takes many years to turn a patented discovery in the laboratory into a drug that is approved for clinical use. Only after clinical trials have shown that the drug is safe and effective will it receive the necessary regulatory approval to enter the market. Even then, in the UK, it will have to be approved by NICE before it can be widely prescribed in the NHS.
So, by the time the drug reaches this stage, it may only have a few years of patent life left before it can be manufactured as a generic product by any drug manufacturer.
How can we trust research funded by drug companies?
Clinical trials are essential for a new drug to gain regulatory approval and they are expensive — the average cost of a phase three clinical trial in cardiovascular medicine is about $27m. Consequently, such trials will necessarily be funded by the drug company concerned. So, given the circumstances, how can we trust the outcome of clinical trials that are funded by a drug company that desperately needs a positive outcome in order to gain regulatory approval?
The answer lies in the way the trial is run. The real issue is not who has funded the study — only the drug company can afford to — but who has designed and conducted the study. Many of the large outcome studies in the statin field were ‘investigator-led’, which means that although the drug company funded the study, it was designed and run by an academic research team that collected and interpreted the data independently of the company.
Generally speaking the investigators involved are world leaders whose reputations have been built on running objective, bias-free clinical trials. In addition, good practice dictates that such studies have data monitoring and safety committees that scrutinize the data independently of those actually running the trial.
The current drug discovery and development model is unaffordable and unsustainable.
It is fair to say that many, both inside and outside the pharmaceutical industry, agree that the current model of drug discovery and development is unaffordable and unsustainable, and considerable thought and energy is currently going into how a better system can be developed, but as yet there has been no major breakthrough. So, for the foreseeable future, trials on new drugs will continue to be funded by the company aiming to bring that product to market.
So what is the BHF’s approach to clinical trials?
Because BHF professors are world leaders in their particular aspect of cardiovascular disease, several of them have, over the years, led major clinical trials that have changed clinical practice.
•BHF Professor Peter Sleight and colleagues in Oxford who undertook the ISIS studies that established, among other things, the role of streptokinase (a clot-busting drug) in the treatment of heart attacks
•BHF Professor Stephen Ball at the University of Leeds who led the AIRE study that demonstrated the life-saving benefits of the angiotensin converting enzyme inhibitor (ACE inhibitor) ramipril in patients with heart failure
•BHF Professor Sir Rory Collins at the Oxford Clinical Trial Service Unit who led the Heart Protection Study that showed how simvastatin could reduce the risk of a future heart attack or stroke in high risk people
•BHF Professor Keith Fox at the University of Edinburgh who has been a senior investigator on several major clinical trials of drugs that have improved outcomes for patients with suspected or confirmed heart attacks.
Clinical practice changed around the world
Together, these trials have led to worldwide changes in clinical practice and hundreds of thousands of lives saved and have undoubtedly contributed to the massive reduction in deaths from cardiovascular disease that has occurred in the UK over the past 50 years. All these studies received some drug company funding.
But the BHF’s main contribution to clinical trials comes when the patent on the drugs concerned expires and they become cheaply available.
It is then that BHF-funded investigators can design affordable (for the BHF) studies that compare different generic drugs to establish how best to use them wholly independently of any industry input, financial or otherwise. The PATHWAY studies on the best way to treat resistant high blood pressure are a good recent example of such impactful studies.
Minimising conflicts of interest
If we want new and more effective drugs we must acknowledge the pivotal role that drug companies play and we need to have mechanisms that ensure that true conflicts of interest are minimised when it comes to the evaluation of their products. For the investigators running clinical trials it is both necessary and appropriate that the money to run the trial should come from industry.
But this should not be perceived as a conflict of interest provided the data are handled appropriately and there is no personal financial gain for the investigators involved. When it comes to conflict of interest, there is a world of difference between an academic group that receives money from a drug company to run an objective clinical trial and doctors who receive a personal income from drug companies in return for giving lectures about their drugs or to provide marketing advice.
In the meantime, solely with public support, the BHF will continue to fund the pioneering laboratory science that the pharmaceutical industry can turn into the next medical treatments for heart disease. And we will ensure we can independently assess those treatments so patients and the public get unbiased advice about their benefits and risks.