Drug Regulation

The Problematic Advocacy that Portrays Bedaquiline as a Wonder Drug


On June 22, 2018 the Wire re-published my last piece, along with a rejoinder by Anand Grover, in our ongoing debate on the manner in which Bedaquiline was approved by the DCGI after waiving Phase III clinical trials. Grover ends his piece with the following dramatic question:

“The question is, if the use of bedaqualine is going to cure two out three persons, and in its absence, they would face certain death, would any reasonable medical person withhold that drug from those persons. That is question that the learned professor, Mr. Prashant Reddy, has been avoiding and would like to avoid, but needs to answer.”

I am amazed at the degree of exaggeration in Grover’s commentary on bedaquiline. I cannot understand why Grover describes this drug as a life-saving wonder drug that is going to cure two out of three persons. For the record, there is at least one Nobel prize winner who has cautioned against the portrayal surrounding bedaquiline. Speaking at the Lindau Nobel Laureate Meeting, Sir John Walker who won the Nobel Prize for Chemistry in 1997 had categorically warned against classifying bedaquiline as a wonder drug. The accompanying photograph of his presentation was tweeted by Divya Rajagopal a reporter from the Economic Times who was attending the conference.

In an interview with Divya Rajagopal, the Nobel laureate reiterated his caution against using the drug on a large patient population until there is more data on the drug’s side-effects. His statement to the ET is as follows: “One should always be cautious when it comes to using new agents like these. There might be unforeseen circumstances that may arrive yet because clinical trials (that) have been conducted have been quite limited, with only phase 2 clinical trial with 440 people. So, it would be unwise to use in large populations,”.

Referring to the roll out of the drug in India, the ET report states “This is what has alarmed scientists like Walker. “We should wait for more data to emerge. You have to approach in a step-wise manner and expand gradually once it becomes clear if there are not any contraindications,” he said.”

The confidence that Grover and others repose in bedaquiline

 Grover’s claim that patients without access to the drug is incorrect. Like many other activists, Grover is under the impression that bedaquiline is the only drug out therefore MDR or XDR patients but the fact of the matter is that we have no data on how bedaquiline works in isolation. This is because the only published studies have used bedaquiline as part of a multi-drug combination to treat patients. The phase II study of bedaquiline published in the New England Journal of Medicine explains that the treatment plan for the study involved a combination of known drugs for two groups of multi-drug resistant patients. In addition, one group was given bedaquiline, while the other was given the placebo (a dummy pill). The group that was given bedaquiline plus the regular combination of drugs showed a cure rate of 58%, while the other group that was given the regular combination along with a placebo showed a cure rate of 32%. The difference in cure rates for both groups was 58% and 32% i.e. the group that got bedaquiline showed a cure rate that was 26% better than the group that got the placebo. These results tell us that Bedaquiline has promise but only a 26% better outcome than existing treatment regime. The problem however, as reported by the same study is that the group that got bedaquiline showed a higher death rate (10 patients died but no causation has been established) and also reported Qt-interval prolongation for bedaquiline (i.e. an effect on the heart’s electrical activity).

The question now for the medical community is – Does the 26% increased benefit in adding bedaquiline to the treatment regime compensate for the possible side-effects of the drug? The regular practice, as established by law and convention, is to conduct Phase III trials on a larger set of patients to generate better data for regulators and medical community so as to enable them to make an informed decision. The challenge is to generate data that show that the advantages of bedaquiline outcome not only its own side-effects but also that it is significantly better than existing drugs used to treat MDR-TB. This is why Phase III trials are so important, which is why some of us are amazed at the decision of the government to waive Phase III trials entirely.

What I find more surprising is the confidence with which activists like Grover speak about the drug when it is so clear that there is risk associated with bedaquiline and when there are other treatment options for MDR and XDR patients. Grover isn’t the only one who is so confident. A few months ago, I was tweeted, in response to similar issues that I raised about bedaquiline, the following tweet by a charming young chap who claims to be handling MSF’s social media handle. (I couldn’t confirm this because MSF’s India head Leena Menghaney did not reply to my email asking for a confirmation whether he worked directly for MSF). What surprised me about the tweet, apart from the language, was the confidence with which this chap states that Phase I & Phase II trials are good enough to scale up the usage of the drug. He is most likely repeating arguments he has heard in the MSF office.

Chapal Mehra and the advocacy around bedaquiline  

In a bid to understand what led to the incredible confidence in bedaquiline, I decided to research the writings about the drug in the Indian media. The one name that popped up frequently was that of Chapal Mehra. He has written a few pieces on TB survivors and several of these pieces slip in references to bedaquiline as the silver bullet to treating TB patients. He is also quoted as a public health specialist by health reporters writing on TB.

Sample this paragraph from an op-ed Mehra wrote for Huffpost:

“Sitting in his one-room house in Dharavi, on a rainy Mumbai morning, Owais, India’s first patient to be put on Bedaquiline, one of the newest drugs in the arms race against DR TB, once asked me, ‘Who would have been responsible if I didn’t receive this drug?’ In this one question, he sought the answer that most of the TB-affected in India want to know: Do their lives matter? And if so, who is accountable?”

Here’s another extract from a piece he published in BMJ:

“How do poor patients survive in this climate of apathy? Who responds to their needs? I recall interviewing the first patient to be put on bedaquiline at Hinduja Hospital in Mumbai—a city considered the epicenter of drug resistance in India. He spoke movingly about staring death in the face and the hope this drug provided to him. There are thousands like him in India alone, though most cannot access or afford this drug. Who will give them hope?”

In a piece for the Hindu he states:

“Access to new drugs like Bedaquiline is best explained in the struggle of an 18-year-old girl who desperately needed the drug and went to the Supreme Court to get it. Had she got this treatment sooner, she may not have died.”

A ToI reporter from 2014 quoted Mehra making the following statement on bedaquiline:

“Chapal Mehra, an activist working with civil society groups on TB, wants the government to lay down protocols to avoid misuse. “Considering India’s rising drug-resistant TB burden, access to new drugs like bedaquiline is essential,” he said.”

Another piece published in the Huffpost stated the following:

“With the tests revealing extreme resistance patterns, Udwadia chose to put her on Bedaquiline—a new drug— obtained with great difficulty through a compassionate use program. Tejal responded to Bedaquiline well. “It wasn’t as difficult a medicine to take. None of the side effects were extreme and I began to feel better.” Her tests, six months later, revealed she was sputum negative for the first time in almost two years. For the first time, Tejal was hopeful of a TB-free future.”

Another published in Scroll where he states:

“In September 2013, he finished the Bedaquiline course and his tests came back completely clean. Despite this, Owais kept taking category three drugs because of the previous reappearance of the disease. In March 2015, he finally stopped TB drugs completely-almost a decade after he began treatment.”

The piece in Scroll published a disclosure that the piece was an extract from Mehra’s book titled ‘Voices from TB’ and that his work was supported by the Lilly MDR TB Partnership. The Lilly MDR foundation was setup by the pharmaceutical company Eli Lilly in partnership with the World Health Organisation (WHO) to ramp up efforts to fight TB. Pharmaceutical companies funding patient advocacy efforts is not a completely unknown phenomenon in the West. It was recently reported that pharmaceutical companies donated $116 million dollars to patient advocacy groups in the West, in a single year.

I first encountered Mehra when I wrote to the ‘Survivors Against TB’, a patient group that describes itself as “Survivors Against TB is a community-based movement led by of a group of TB survivors who are working to strengthen India’s fight against TB.” It has petitioned the government for better access to bedaquiline. I had written to the group while researching for the first set of stories I published on SpicyIP with Balaji. I received a reply from Chapal Mehra offering to talk over the phone. I did not take him up on the offer since we had managed to collect enough information to write the first set of pieces that we published in March. I did however start researching to understand how SATB worked and the role played by Mehra who is described as the group’s convenor. It appears that some point he was working with Global Health Strategies, an international firm that describes itself as follows: “GHS uses advocacy, communications and policy analysis to advance issues and power campaigns that improve health and wellbeing around the world.”

As per information that I could find, he was supposed to work as a project director for REACH, a NGO where has was to be a Project Director to implement the “TB Call to Action” a project that was funded by USAID and supported by another international NGO called KNCV which is based in Netherlands. The Chairperson of REACH, which is based out of Chennai, is Dr. M. S. Swaminathan (father of Dr. Soumya Swaminathan who was the Director General of Indian Council of Medical Research and presently a Deputy Director General at WHO – she was involved in framing guidelines for bedaquiline’s rollout in India and also wrote the introduction to Chapal Mehra’s book). REACH has received sizeable contributions from USAID and KNCV for TB advocacy. USAID is an American government body and has been involved in India’s TB program for several years now. One of its current programs, apart from the ‘TB Call to Action’, is a joint effort with Janssen to contribute bedaquiline to the Indian Government.

I did write to the email ID run by ‘Survivors Against TB’, asking Chapal Mehra for details about his funding and his advocacy around bedaquiline. I did not receive a response to my email sent to him on June 19, despite a reminder. I am reproducing the email below:

“Dear Chapal,

As you may know, I’ve been writing on the bedaquiline issue. I’m examining the advocacy around the drug and I’ve learned that you have been working for REACH – a NGO that receives funding from USAID for TB advocacy and I was hoping you could respond to some of the following questions.:

(i)  Do you continue to work with REACH and have your writings on bedaquiline been a part of the USAID advocacy project?

(ii) Have you received funding from any other pharmaceutical company or foundation supported by any other pharmaceutical company to write about bedaquiline?

(iii) From where does Suriviors Against TB receive its funding?

(iv) Do you disclose the source of your funding to editors who publish your opinion pieces related to bedaquiline?

Thank you,

Prashant”

If Mehra replies I will publish his reply.

That aside, I presume a lot of people may not be too happy about pharmaceutical companies or USAID funding advocacy efforts like the “TB Call to Action”. Personally, I don’t think it’s a problem because patient advocacy groups play an important role in the public health debate and there is very little funding for such efforts in India. However, I do think transparency is a must because a writer disclosing a pharmaceutical company or its foundation as a source of funding will likely be subject to higher levels of scrutiny and that is a good thing.

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Prashant Reddy

Prashant Reddy

T. Prashant Reddy graduated from the National Law School of India University, Bangalore, with a B.A.LLB (Hons.) degree in 2008. He later graduated with a LLM degree (Law, Science & Technology) from the Stanford Law School in 2013. Prashant has worked with law firms in Delhi and in academia in India and Singapore. He is also co-author of the book Create, Copy, Disrupt: India's Intellectual Property Dilemmas (OUP).

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