I read the recent bedaquiline debate on The Wire with much interest. While the learned advocates make key arguments in favour of and against the use of bedaquiline in India, they have taken somewhat extreme positions. The truth – and the ethically and scientifically correct process that the Indian government and practitioners perhaps need to follow – lies somewhere in between. For that, we ought to understand the precepts of the concept of expanded access first.
The US FDA introduced the Expanded Access programme, also referred to as Compassionate Use, in the 1970s to avail patients of an Investigational New Drug (IND) that is not yet approved for general use. The US FDA describes the scenarios under which the programme can be utilised as follows.
–Patient has a serious disease or condition, or whose life is immediately threatened by their disease or condition.
–There is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition.
–Patient enrollment in a clinical trial is not possible.
–Potential patient benefit justifies the potential risks of treatment.
–Providing the investigational medical product will not interfere with investigational trials that could support a medical product’s development or marketing approval for the treatment indication
The programme can be utilised to give access to an IND to individuals, small groups of patients or large groups of patients. The key part of the procedure to prescribe an IND, besides FDA agreement, is informed consent by patients after they have understood that the drug is not approved by the FDA and that the risk-benefit ratio of such a “last resort” intervention is unclear.
The Indian government seems to be rolling out bedaquiline in a phased manner and somewhat along the lines of the US FDA Expanded Access. It is being provided at specific centres and after a recommendation by a practitioner who understands the pros and cons of such a treatment. However, as Prashant Reddy has rightly pointed out, and Anand Grover also repeats, the consent form used by the government is awfully inadequate. Unfortunately, Reddy falters by arguing that all patients who receive bedaquiline could have been enrolled in clinical trials. Such an endeavour would be impractical plus it is highly unlikely that all patients would meet stringent inclusion criteria that clinical trials usually have.
The role of DCGI and the government
The case of bedaquiline is quite unique. The US FDA approval in 2012 created enough controversy that the New England Journal of Medicine ran a perspective piece addressing the issues involved. But the Indian government and practitioners will be faced with such situations in the future again where a drug of high importance is approved without very long-term data elsewhere and there are no local clinical trials.
The Indian government and DCGI already have a programme along the lines of Expanded Access but it needs to be more robust and better outlined. It needs to be better implemented including with significant improvements in the all-important informed consent process. Additionally, the practitioners, patients and the public at large need to be made more aware of such a program. Such interventions will obviate the need for excessive legal intervention and put the patients and practitioners in the drivers’ seat with DCGI oversight.
Since publication of the above piece, I have received feedback that my arguments are disingenuous specifically in reference to the impracticality of providing bedaquiline via clinical trials only.
I provide clarification as below.
Clinical trials would be the ideal manner in which Indian patients are provided bedaquiline. But expanded access has an equally important role. My disagreement with Reddy is regarding his assertion that all patients who receive bedaquiline could be part of a trial.
About 1000 Indian patients have received bedaquiline in India but the program is being expanded to 10,000 patients. This is a large number of patients to be included in clinical trials. Moreover, the drug is to be prescribed at 140 centres through expanded access. Clinical trials usually have a much smaller number of centres that participate. A patient may not meet inclusion criteria for a trial simply due to the small number of trial centres and inability to travel to the closest trial centre for multiple visits because of distance. Such a patient would have the option of getting the drug via expanded access. Another example of a patient not meeting the inclusion criteria for a trial would be age limit. For example, if a trial has an age limit of 18 to 65 years, a 17 years and 11 month old patient may not be able to enrol. But that same patient could possibly get the drug via expanded access, if deemed appropriate. Also, take the example of one of the trials currently testing bedaquiline in India, according to online clinical trials registry. Not all arms of this trial are to give bedaquiline to enrolled patients. Expanded access would provide the bedaquiline option to a well-informed patient who absolutely wants to try the said drug and not go to an arm in a clinical trial which utilises other drugs. There are many other possible scenarios where expanded access may meet the desires and needs of a patient that a clinical trial otherwise would not be able to fulfil.
Disclaimer: The author is a Los Angeles based practitioner and is a site principal investigator for a multiple sclerosis drug trial sponsored by Novartis and a seizure drug trial sponsored by Neurelis.
Jay Desai is a neurologist.