India’s drugs regulatory office, the Central Drugs Standard Control Organisation (CDSCO), recently issued a raft of notices on the subject of clinical trials and drug safety.
While the sheer number of them – 14 ‘orders’ dated July 3 – does raise an eyebrow or two, the communiques are noteworthy as they address issues that have turned clinical trials and drug safety in India into a lightning rod for controversy. The orders are based on a report of an Expert Committee headed by Dr Ranjit Roy Chaudhury and set up by the Health Ministry “to formulate policy and guidelines to approve new drugs, clinical trials and the banning of drugs.” Here’s my view on some of these orders.
Capping the number of trials per investigator
The regulator orders that no investigator should take on more than three clinical trials at a time. A ceiling is welcome. I distinctly recall a meeting some years ago, with the CEO of a clinical research organisation. There was a shortage of experienced investigators, he complained, and the sought-after few demanded ever-higher fees. (I’m still unsure what distressed him more – the ethical implication, or the financial one).
Given the extensive oversight, and documentation that a trial requires (not to mention time), it is not every doctor’s cup of tea coming as it does over and above standard care-giving. It is rather alarming therefore when trials are spoken of as a matter of financial incentive rather than bandwidth.
Clearly, the regulator thought this a valid concern. Coupled with an earlier notice ordering investigators to disclose financial agreements with sponsors or their representatives such as CROs, the ceiling should help curb inducement and prevent errors that might result from stretched bandwidth. I have no strong views on the number except to say that three appears reasonable.
Technical review committee to, well, “review” proposals
Pharma companies were dissatisfied with the expert committees (classified by disease areas and known as New Drugs Advisory Committees or NDACs) that were set up by the regulator to approve drug trials and marketing. They did not meet often enough and lacked expertise in regulatory data review, companies felt. Their infrequent meetings led to delays. The Roy Chaudhury Committee recommended replacing them with a Technical Review Committee (TRC) that would have experts drawn from pharmacology, toxicology and other disciplines relevant to data review. This Committee would co-opt disease/subject-matter experts as required. The order deviates slightly from this recommendation.
Instead of replacing the NDACs with the TRC, the CDSCO takes the TRC rather literally and makes it a “re-view” committee. The TRC will take a second look at what the NDACs suggest. The NDACs have been renamed Subject Expert Committees (SECs). The logic for this iteration is unclear but at least now there’s another layer of checks and balances. The move suggests that CDSCO is not entirely convinced of the lack of utility of the NDACs (or SECs) but wants to be seen as addressing industry concerns.
However, the threat of delays might still hang over applications unless there is a time limit set on the review process, also recommended by Roy Chaudhury, but not visible in this order.
Stating when a trial is not necessary
Readers may recall that a couple of years ago a Parliamentary Committee had launched a scathing criticism of the drug regulator’s office for approving new drugs in India without a single local trial though rules require a limited safety and efficacy trial even if the drug is sold in another country.
In 2013, the government reportedly said that 26 new drugs had been approved this way since 2010. It defended its decision stating reasons of emergency and the absence of a sufficient number of patients to conduct meaningful trials. But this still smacked of that ugly word “discretion.”
The CDSCO has now enumerated the conditions when a trial will be deemed unnecessary for a drug approved outside India and being launched for the first time in the country. These are cases of national emergency, extreme urgency and epidemics, and while approving orphan drugs (for rare diseases) or diseases where there is no therapy.
This begs the question – on whom does the burden of proof lie? The regulator or the company? Is the exception granted proactively – in the form of a positive list of drugs/categories or is it sought by a company? Also, the term ‘orphan’ drugs (borrowed from the US FDA’s book) should be defined for this is new to the Indian regulatory setting, as far as I know. The regulator may also be required to clarify terms such as “extreme urgency” and “national emergency” even if it is only to state that it agrees with the Roy Chaudhury Committee’s definitions of them.
Banning of unsafe drugs
After the fiasco surrounding diabetes drug pioglitazone last year – banned and then put back – this order is welcome. It clearly states that if two or more countries ban a drug for reasons of either safety or efficacy the regulator will review the drug in India. In the past, the CDSCO had shilly-shallied on the subject – sometimes taking the lead from regulators in Europe and sometimes the US. Since the two regulators do not co-ordinate their actions and often take opposing views, this caused a good deal of controversy. The current order gives direction but still does not answer the main question. When will CDSCO ultimately ban a drug. Will it have a bias towards any one foreign regulator’s actions?
Since the Roy Chaudhury Committee report was pretty exhaustive, I believe there may still be more from CDSCO. In the meantime, there’s enough to chew on.
Before I sign off, I’d like to register a strong protest against the atrocious grammar used in these orders. I urge readers to humour me and read this sample. My eyes crossed by the time I reached the end – a side-effect for which I demand compensation. Try making sense of it. I am too busy trying to see straight again.
Pic sourced from http://www.clker.com