Outsourcing clinical trials
If Union Carbide taught us anything, it’s that we don’t, truly, care so much about catastrophic outcomes when they’re in other countries.
During the 20th century, clinical trials – for many years a legal necessity to demonstrate that experimental medicines are safe and effective before their approval – were predominantly conducted on patients in North America and western Europe, close to companies’ scientists, regulators and principal markets. Since 2000, however, the expansion of western pharmaceutical companies around the world and the emergence of local rivals in developing countries have meant that the number of trials taking place in the emerging economies of China, India, eastern Europe and Latin America is catching up.
recruitment in western markets is increasingly difficult and costly. Patients are generally willing to participate in Phase 2 and Phase 3 trials, designed to measure efficacy, assess the appropriate dose and identify any side effects. But for rarer diseases, including for many cancers, the number of patients who are not already enrolled in trials for rival new drugs is limited – and the cost of finding them high.
By contrast, a number of the emerging markets offer good and improving medical infrastructure, at least for a significant proportion of their population, supported by well-trained doctors and assistants available at a fraction of western salaries – including many who speak English and were partly educated in the west. That can reduce the direct costs of trials by half or more.
Just as important, such countries offer large pools of patients willing to be tested, including many who are “treatment naive”, because the relatively low standard of healthcare compared with western countries means they have not had access to the latest and most expensive medicines.
Trouble is – and anyone who read or saw the Constant Gardener will, with all their cynicism intact, not be surprised, just because a cost can be saved, doesn’t mean that it should. Just as it was in Bhopal. The Financial Times provides this handy diagramme:
Transferability and generalisability are also serious issues. There are two key questions to be applied to clinical trial results: 1) Was the trial representative of the population to which the treatment will be offered? Will the effects measured be generalisable in the population? 2) Was the trial structure representative of the treatment delivery structure in the population? Will the effects measured be transferable to patients in the real world?
Odds are that, if the trial for a US-bound pharma product for a rich-man’s-burden kind of disease took place in Bihar, the answers to those questions will be no – in which case the uncertainty surrounded the results, ex poste, are probably unacceptably high for FDA, PBAC, NICE, etc.-level approval.
The FT also offers an impressive ethical dilemma:
Another is that patients may be unduly coerced to take part because a trial offers access to medical care they could not otherwise afford; and because they may lack adequate “informed consent” to understand they are taking risks by using an experimental medicine – or from receiving a placebo rather than the new drug.
A third concern is the lack of post-trial access to medicines. The country where a trial is conducted may not gain access until long after the drug is approved in the west. Often even the patients on whom a medicine is successfully tested are not guaranteed that they will continue to receive it once a trial comes to an end.
Pretty interesting debate, well-handled by the FT.