By Jerome Burne
Generally we don’t trust utopias. If they don’t remain fantasies but emerge into the real world, we expect them either to rapidly descent into rigid authoritarian hells or to disintegrate into factions and unproductive chaos.
So it’s remarkable and exciting to discover a functioning utopia that is over 50 years old and still holding out the possibility of creating a better world. In this case, by providing a blueprint for transforming medical research and carrying out a badly needed upgrade of the way drug are trialled and tested.
It’s no secret that our current system is in urgent need of an overhaul. It provides us with pills that are hugely expensive and creates a perverse and dangerous incentive to exaggerate benefits and conceal dangerous side-effects. With perfect logic companies refuse to investigate any treatment that isn’t patentable and then stamps “for our eyes only” all over the raw data it gathers in its drug trials. All combine to create a business model that can reasonably be accused of putting profits before patients.
The utopia which shows us that an alluring alternative exists comes in the form of the little-known, at least to the general public, clinical research institute in Milan called Mario Negri Institute for Pharmacological Research. Astonishingly its founding principles, set out in 1963, provide patient-friendly solutions to all those problems.
The solution to Bad Pharma
The story of how it is possible to thrive, win international recognition and put the health of the public first, is told in a new book called Good Pharma: the Public-Health Model of the Mario Negri Institute (Palgrave 2015), which is intended as a solution to the multiple drug company failings set out in Ben Goldacre’s best-seller ‘Bad Pharma’.
A mission statement from the early days of Mario Negri is still a good description of the way the Institute works today: ‘To do research of international quality, to improve people’s health based on independent, transparent science and openly to educate doctors and patients about how best to address their health needs.’
The starting point for doing things differently is at first sight impossibly radical and impractical. Yet it works. Mario Negri doesn’t patent any of its discoveries.This effectively removes that hugely damaging perverse incentive at a stroke. At the moment drug company labs are almost exclusively devoted to finding new molecules that can be patented and then turned into drugs
These then have to be heavily promoted to maximise sales until the patent runs out, at which point a new patentable molecule has to be developed for the production line. In such a system there are huge pressures to keep very quiet about the possibility of dangerous side-effects
In fact should drugs be patented at all?
Refusing to patent in today’s economic climate seems absurdly altruistic. So it’s worth pointing out that you couldn’t patent drugs in much of Europe for decades because they were regarded as ‘societal goods’ like water or the fire service. It’s an idea that has a lot to recommend it. The companies defend patents on the grounds that they stimulate innovation, vital for getting new, life-saving drugs to market.
But that’s not what the evidence says. One of the authors of Good Pharma is Donald Light, professor of comparative health care and an economic and organizational sociologist at Rowan University School of Osteopathic Medicine in New Jersey. His research has found that in 1970 15% of new drugs were genuinely innovative, but by 2000 the rate had dropped to 8%. Rather than stimulating innovation patents encourage companies to produce a stream of ‘new’ drugs that offer little or no improvement on what is already available. They are “me-too” drugs, developed only to obtain a fresh patent that enables them to charge massive prices.
By not patenting any new molecules, the Mario Negri’s researchers don’t have any vested interests in the drugs they are testing. So they can take just as much care investigating possibly damaging side-effects as they do establishing benefits. A key part of their trials is a full review of what is known about a drug so far. Done regularly it could significantly cut the damage done by drugs.
Reducing the death toll from drugs
When the risks of various patented drugs finally come to light years after being licenced, such as the painkiller Vioxx or the diabetes drug Avandia, it usually turns out that warning bells had been ringing from the beginning. The stream of misleading trials is one of the reasons why prescription drugs are estimated to be the third or fourth leading cause of death. Adopting the Institute’s approach could begin to dramatically reduce this level of harm.
The Institute earns its money the old fashioned way, by competing and winning grants and contracts from governments, academic institutions and drug companies. Since the 1960s, the Mario Negri Institute has won grants and contracts from the National Institutes of Health in America which also has a tradition of doing non-commercially driven research and the charitable Wellcome Trust in the UK. Today the Institute occupies a site of almost half a million square feet on the outskirts of Milan with nearly 200 researchers and is involved every year in over 100 clinical trials with over 85.000 patients.
Another surprising patient-centred principles of the Institute is to refuse to run placebo controlled trials if an effective drug or other intervention exists (including surgery, supplements, or a good diet). It considers such trials unethical because they provide no useful information for patients or clinicians who don’t want to know if a new drug is better than nothing but if it is better than the best currently available.
The one questions regulators rarely ask
It’s a test that the great majority of new drugs would fail, which are likely to be more damaging than existing ones because the relatively short trials needed to obtain a licence, don’t tell you about the inevitable problems that emerge when they are taken by millions for years.
And the Institute avoids another misleading failing of the commercial approach. While companies routinely test drugs on patients who are younger and healthier than the people who will actually be taking them, it tests drugs on patients who are likely to be prescribed them.
‘The only question that matters,’ says Professor Silvio Garattini the charismatic director of the Institute. ‘is whether a medicine better for patients than an existing treatments. Conveniently for the drug companies this is the one question that the regulators do not usually ask or answer.’
As well as providing valuable information to patients, running such ‘comparator’ trials could dramatically lowers research costs because all those copy-cat, placebo controlled trials that are only required to show a new drug is better than nothing become redundant. In fact, the way research is done under the present system is very wasteful and inefficient according to Professor Iain Chalmers, who wrote the Forward to the book.
Very few trials provide useful clinical information
Chalmers is the founder of the independent Cochrane Collaboration which reviews the evidence for treatments and his research shows that 85% of investment in pharmaceutical and medical research is wasted. By contrast the Mario Negri Institute ‘represents a radically safer, less costly and more sensible alternative to the commercial goal of getting as many patients on patented drugs as possible.’
The practice of checking for potential risks in the literature before running tests and making sure drug is a genuine improvement, avoids wasted trials and provides much more clinically useful information. At the moment out of the 165.000 registered clinical trials, fewer than 10% provide information that is useful to doctors and patients.
Without a vested interest in drug profits the Institute is also free to recommend that patients have the lowest possible dose of any drug for the shortest possible time. Unlike the current system where prescription rates rise inexorably and patients are frequently left taking a drug for years.
Putting the spine back into drug regulation
Other influential projects of the Mario Negri Institute described in Good Pharma include identifying drugs with little or no benefit reimbursed by the Italian NHS. When the Institute leaders cut those drugs in the 1990s, national expenditures on drugs dropped 30%. Still ongoing is a campaign to push the European Medicine’s agency to set more rigorous standards for licencing drugs and to challenge drug company claims that information they collect from patients during trials is protected by commercial confidentially and instead to make it available to other researchers.
One of the ways the Institute preserves its independence is not allowing any organisation to provide more than 10% of its income.The value of this became clear recently when GlaxoSmithKline reneged on a promise of transparency and would not allow Mario Negri researchers access to their own data gathered during a trial. Rather than continuing under tighter restrictions the Institute walked away, losing the potential of earning millions of dollars as a result.
It’s very unlikely that the companies are going to sign up to patent-free drug development anytime soon but what Mario Negri shows is that that it is possible to survive and provide more reliable and clinically relevant data without patents.
In the UK the obvious niche for a Mario Negri clone would be as part of Public Health England. As well as raising research standards it might go some way to putting an independent spine into our regulatory system which long ago surrendered to corporate capture. It might not usher in a full –blown utopia but it would have to be a great improvement.
Good Pharma: The Public Health Model of the Mario Negri Institute by Donald W Light and Antonio F Maturo. (PalgraveMacmillian £59.50.
Through November, Palgrave is offering a 30% discount. To obtain it email email@example.com, asking for the book by title, providing your physical shipping address and quoting the code PM15THIRTY