Tweaks to the R&D pipeline could create new drugs and greater benefit for patients
Pharmaceutical companies 'underinvest' in long-term research to develop new cancer drugs owing to the greater time and cost required to conduct such research, finds a newly published study co-authored by economists at Massachusetts Institute of Technology (MIT) in the US.
Specifically, drugs to treat late-stage cancers are less costly to develop than those for earlier-stage cancers, partly because the late-stage drugs extend people’s lives for shorter durations of time. This means that the clinical trials for such drugs are also completed more quickly — and provide drug manufacturers with more time to control patented drugs in the marketplace.
'There is a pattern where we get more investment in drugs that take a short time to complete, and less investment in drugs that take a longer time to complete,' says MIT economist Heidi Williams, co-author of a new paper in the American Economic Review, Do Firms Underinvest in Long-Term Research? Evidence from Cancer Clinical Trials, that details the study findings.
The social cost is significant; the researchers estimate that the lack of investment in longer-term drugs resulted in a loss of 890,000 life-years among people diagnosed with cancer in 2003 alone. The paper also suggests three policy adjustments that might produce more long-term research on anti-cancer drugs.
The finding 'doesn’t mean that the private firms are doing anything wrong,' Williams adds, given the incentives they face. However, she observes, 'the public sector is more willing to invest in these long-term projects than is the private sector', suggesting that new policies could produce more types of drugs for patients.
There is a pattern where we get more investment in drugs that take a short time to complete, and less investment in drugs that take a longer time to complete
The researchers analysed four decades of data from a variety of sources, including the National Cancer Institute, which has a registry of clinical trials and data on cancer incidence and survival in the US, and the US FDA, which approves anti-cancer drugs. The study encompassed more than 200 subcategories of cancers detected at different stages of development.
Before reaching their conclusions, however, the researchers had to establish that the tendency toward short-term drug research was due significantly to the shorter duration of clinical trials. They concluded this, in part, by studying what happens when clinical trials do not use mortality to establish effectiveness, but instead use 'surrogate endpoints' — that is, biomarkers that stand as proxies for eventual outcomes and help estimate how effective the drugs will be.
By examining the historical data, the researchers found that in some cases where surrogate endpoints are allowed in cancer research clinical trials — including many types of leukemias — there were relatively more trials and money poured into research.
The authors suggest three new policy approaches that could spark the development of a greater number of long-term cancer drugs. The first is continued use of surrogate endpoints — or at least, initially, more research to find out if wider use of surrogate endpoints for additional cancers is valid.
The second policy change is more public funding of research and development for anti-cancer drugs, since such funding is free of short-term, private-sector shareholder pressure to produce returns. There are only six cancer drugs in existence that are preventative in nature — and all six have been developed because of public funding, or relied on surrogate endpoints.
Williams thinks these two points are related, stating that 'no individual private firm wants to come in and provide all of the evidence that you need to validate a surrogate endpoint, because once one is validated, that’s going to be used by all of the firms on the market'.
A third potential new policy would be changing the terms of drug patents, which typically run from the time of patent filing, to run from the time when the drug hits the market. That said, the FDA can currently grant exemptions that lengthen drug patents to account for the time R&D takes.
Williams emphasises that, as economists, she and her colleagues are only advocating the use of surrogate endpoints where they have been accepted by the consensus within mainstream medicine.
'We’re not attempting to be doctors,' she says.