19 Sep, 11 | by BMJ Group
There is increasing pressure for drug regulators to provide quicker access to new drugs. The pressure comes from doctors, patients, politicians, and the drug industry. What is likely to happen? Will patients get quicker access to new drugs?
A month ago an oncologist proposed in the New England Journal of Medicine that oncologists should be able to use drugs immediately after phase I trials—that is, when it’s been established that the drug can be given to humans and before it has been tested in clinical trials. The oncologists would then collect data on the patients they treated—and a quick decision could be made on whether the drug was useful.
Alasdair Breckenridge, chair of the Medicines and Healthcare products Regulatory Agency, told the audience about the suggestion of the oncologist at a conference to celebrate 50 years of the Mario Negri Institute. He also pointed out that 2011 is the 50th anniversary of the letter in the Lancet first describing the effects of thalidomide. Silvio Garattini, director of the institute and described by Breckenridge as a “hellraiser,” said that what the oncologist was proposing was what happened in Italy more than 50 years ago when a drug was licensed once five doctors had prescribed it.
President Obama has, meanwhile, attacked the Food and Drug Administration for being ill equipped to handle new biological entities and medical advances. Politicians are responding to patient pressure to get quicker access to new drugs, but they are also concerned about economic growth. They fear that excessive regulation is blocking innovation and the appearance of new products that can be sold to the world.
Pharmaceutical companies are no doubt lobbying politicians on this point—because they have a productivity crisis. They are investing ever more in research and yet producing steadily fewer new drugs. There were 40% fewer new drugs last year than in 1999. Investors, said Eddie Gray, president of pharmaceuticals Europe of GlaxoSmithKline, are becoming “less enamoured” with the pharmaceutical industry, and last year saw the first ever drop in global spend on research and development by the industry. When Pfizer announced the closure of its research centre in Sandwich its share price rose.
The industry, he and others said, has to find a new way to do business. The old way of blockbuster drugs for common conditions is ending. The future is about targeted (even personalised) drugs, and the regulatory system needs to change as the business changes.
Breckenridge said that the old system had worked well for the past 50 years, but he accepted that the system is no longer successful: regulators have raised the bar on safety progressively; new regulations are added but old ones are not removed; drug development has become longer and more expensive; and the system is designed primarily for new chemical entities when increasingly new drugs are biological products.
So he thought that regulators would be pushed into developing an early access model—perhaps one where the drug is made available earlier to defined groups of patients where benefits will clearly outweigh risks. As is a tradition at the Mario Negri, he thought boldly and wondered about more self-regulation by industry and developing a system for drugs more like that for medical devices.
Garattini was against early access, arguing that “Once the drug is on the market it will be hard to pull it back.” He worried that without randomised trials, drugs with few or no benefits would be on the market and that some drugs with real benefits would be withdrawn because they happened to have serious side effects in the first patients in which they were used. “There are no short cuts, we need randomised trials” agreed Barbara van-Zweiten-Boot, a Dutch regulator. Garattini, who said that half the drugs on the market have no benefit, wanted standards that are not “statistically significant but clinically, or better, patient significant.” He was against surrogate endpoints and said that regulators should insist, for example, with new cancer drugs on six months’ extra life not just five weeks.
Pressurising regulators to agree to early access may not mean earlier access for most patients because most countries in Europe at least have a second stage of health technology assessment. Pharmaceutical companies in Europe can now get a licence to cover all of Europe, but they then have to deal with 27 different health technology assessment organisations. These organisations make different decisions in different ways, but they are concerned with effectiveness (benefit in the real world) while regulators are concerned with efficacy (benefit within trials). The companies would like regulators and health technology assessment organisations to come together and there be just one process for all of Europe, but there was agreement that this was unlikely to happen.
So some select groups of patients (and private patients) may get earlier access to drugs through special licences, but the mass of patients will not.
Competing interest: RS had his expenses paid to attend the meeting where he spoke on “Global public health needs,” a title that almost overwhelmed him. He hardly mentioned drugs in his talk, implying that they are of small importance in responding to global public health needs.
Richard Smith was the editor of the BMJ until 2004 and is director of the United Health Group’s chronic disease initiative.