The Compound Eye

Policy Focus

Clinical Trials Rules in India: 

India accounts for nearly 16.0% of the population worldwide and nearly 20% of the disease burden across the globe, yet less than around 1.4% of total global clinical trials are conducted in the country. Clinical trials are important: not only for testing if new drugs work on Indian population, but also as a source of revenue. Clinical trials if correctly developed would be an additional services revenue to boost our GDP and economy. 

This week has been a mixed bag for clinical trials in India. In one set of rules, new drugs approved for use in select developed markets will be automatically allowed in India if the global trials included Indian patients. These markets include US, UK, EU, Japan and Australia. However, the clinical trials would need to have included Indians. The purpose of these rules is to expedite the availability of drugs validated in other markets. This is excellent news for patients, particularly for those who require orphan drugs. However, a key question that remains is whether presence of Indian individuals in foreign market trials is sufficient to represent the drug response in such a heterogenous population.

Companies have often tried to fast-track their products through local regulatory system - Sanofi tried to get India to waive off Phase III clinical trials for its dengue vaccine. However Indian authorities did not consent and subsequent studies in other countries showed the vaccine could result in severe disease for those individuals who had not been infected prior to the vaccination. This goes on to show the need for thorough testing, a sufficient sample set and accounting for post-market events before a nation wide release of any medical product. However, this rule will preclude the need for clinical trials in India perhaps leaving Indian patients susceptible to adverse events and hampering the clinical trials industry. 

On the other hand, the new rules also incentivise Indian companies to start clinical trials by fast-tracking their proposals. If Indian companies do not hear any status update from the Drug Controller General of India within 20 days, their proposals would be deemed to have been approved. This clarity should help local companies start clinical trials but a more detailed study of the various challenges to holding a clinical trial in India need to be studied to facilitate a significant change in number of clinical trials. 

Further, the DCGI has changed the compensation clause in case of death or disability presumably caused by clinical trials. According to previously drafted rules, 60% of the compensation would have remained non-refundable, even if an expert committee at a later stage found the death or disability was not related to the clinical trial. Now the non-refundability clause has been removed providing relief to clinical trial companies. 

Its Controversial

We need tea cups with built-in thermometers

The news headline that made a splash on 20th March: Drinking hot tea doubles risk of cancer, study finds. 

Now the co-relation of consuming a hot beverage and increased risk to oesophageal cancer has been long known. This study, based in Iran, delved into the exact temperature at which tea could be suspected of causing the cancer. The authors conducted a retrospective study of 50,000 individuals looking at their tea drinking habit and incidence of oesophageal cancer. To judge preference, individuals had to sip tea at differing temperatures (65 C, 60 C and lower) and identify the temperature closest to the one they usually had. Mind you, this is black and green tea which is the most-consumed beverage in the area. Now based on this data, the authors presented findings on cancer incidence in the group drinking tea at very temperature (>65C) and cooler tea (<60 C). As the Daily Mail reported it - drinking hot tea increases risk by 90% or doubles it according to CNN. And that sounds scary! 

However if you consider the actual numbers, cancer incidence in the hot tea group is 87 from a population of 10,799 which is 0.81%. In the cold tea group the incidence was 92 in a population of 19,450 which is 0.47%. The relative risk ratio is no doubt twice for the hot tea group, but the absolute increase in risk is 0.34%. The use of relative risk when the risk of the event itself is too small causes this exaggeration of the result. Further, the authors have not considered other lifestyle factors in their analysis, which means a direct co-relation between drinking hot tea and risk of cancer is weak. 

Yet the story has been represented in media to sound like drinking hot tea significantly impacts risk of cancer. Such sensational headlines are required for increasing viewership, but the mis-interpretation of science can have negative impacts. This is particularly true when papers announce the next cure for cancer, raising hopes of patients and their families, who stand to be disappointed when the treatment does not fail clinical trials. 

Till responsible science journalism becomes the norm, there will always be controversy on what we can safely consume. Till then we need to drink tea from cups with built-in thermometers. 

Science in India

Prioritizing Science for the Nation 

Recently, the academic community was surprised by a circular from the University of Kerala informing that research were to be curtailed to areas of national priorities and faculty were to prepare a shelf of projects for PhD students. A private company is within in rights to control the research areas it funds. So what justifies the uproar if the government decides to interfere in the research it funds? 

The CompoundTake: The fundamental question is: who decides what is national priority? Is enabling an Indian scientist to win the Nobel Prize in the next 25 years a national priority? Is tackling waste management a national priority? Is creating excellent PhD students who can improve science and technology in India and inspire the next generation of scientists a national priority? Is improving S & T contribution to GDP a national priority? The benefits of a thriving S & T community are not limited to publications or commercial solutions, but expand to inculcate scientific thinking, promote intellectual thought and to act as a bridge between society and government on select matters. How then does a government or university decide on what definitively serves national interest?

Instead of identifying national priority areas, it would be more effective for the government to incentivise its focus research areas. Such mission mode commitments are already in play, with 9 new S & T missions being announced earlier this month. Incentivising these missions with increased funding, advanced infrastructure or access to job stability will help attract scientists interested in these areas. 

Tackling issues like waste management or vaccine creation require collaboration across various disciplines; something a single PhD student will not be able to address. Enabling such collaborations between networks of scientists with differing expertise is more likely to contribute to solutions. 

Further the expectations from a PhD student, that of a laboratory and those of a institute are different - off the shelf PhD projects defeats the entire point creating strong independent PhD students. Such priority areas could be created at an institutional level; for example, an institution focussed on issues related to infectious disease outbreaks. 

Finally, prioritising science for national relevance will work effectively only when the nation prioritises its science. Poor funding, complicated policies and lack of job stability for PhD and postdocs need to fixed so that S & T can really contribute to the economic development of our country. 

*Note: I have written this Take from the point of view of life sciences. The conversation is more nuanced: for example, how does life science compare with history on the scale of national priorities? But true across all fields is the importance of nudges. Read here for how these might be shaped in the context of promoting certain areas of research. Lastly, conversations of nationally relevant research are not specific to India; even Australia has been reported to consider a 'national-interest test'. 

Meanwhile, here is some CRISPR news

Electronic detection of Unamplified Target Genes: Kiana Aran and colleagues immobilised CRISPR complexes on the surface of graphene-based transistors. When the complex recognises and binds to the target DNA, there is a change in the conductivity of the graphene material in the transistor. This change can be detected using a handheld device and thus target genes can be identified without the need for any amplification. 

Meanwhile, George Church beats his own record: In 2017, Church and colleagues had knocked out 62 copies of a retrovirus found in pig genomes. Now, the team has successfully triggered 13,200 genetic changes to a single human cell. Why would anyone do this? "To allow for dramatic redesigns of existing genomes, or the flushing out of troves of unwanted, deleterious genetic information from DNA, including retroviruses or redundant genes. Large-scale editing would subsequently enable the engineering of new species, or create clean, foundational genomes that have been stripped down to their most basic elements." I leave it up to you to decide if this is exciting or scary science news. 

Meanwhile, WHO calls for a global registry for gene editing research: The WHO's expert advisory committee has said that proceeding with clinical applications of germline gene editing would be currently irresponsible. However, the committee has not appeared to endorse a ban or a moratorium on germline gene editing. Further, it has called for a global registry to be compiled to list all experiments related to human genome editing. Would this change India's stance on germline gene editing? We will have to wait and see. 

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Shambhavi Naik Research Fellow
shambhavi@takshashila.org.in
080 4372 5304

Takshashila Institution

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