Opinion | The importance of trials in stem cell drugs

The new amendments to the Drugs and Cosmetics Rules of India will be in effect from 13 September. Due to several controversies, allegations of irregularities and protests by health workers against the consent and compensation policies for people undergoing clinical trials, a new drug policy was overdue to facilitate clinical trials in the country.

Maybe clinical trials will get quick permissions under the new setup. The fact that only 1.4% of the world’s total clinical trials are carried out in India, despite the country having 17% of the population and 20% of the disease burden of the world, is both disheartening. It also presents a stumbling block to the government’s efforts to overhaul healthcare in the country. It is also decidedly strange given that conducting clinical trials is a billion-dollar business field.

One remarkable point in the new rule is that it seeks to regulate stem cell-based products as drugs, excluding autologous stem cells, where individual’s own stem cells are collected and minimally treated before infusing them back into the patient.

There are maybe around 300 self-styled clinics offering a range of untested and unproven stem cell drugs in India. Now, they will have to first be backed by clinical trials to prove the safety and efficacy of the drugs, and will then require licences to manufacture and sell. This maybe a milestone in the history of healthcare in the country.

The picture of the cloned sheep, Dolly, a product of stem cell research, graced the cover of the Time magazine in 1997, and opened the floodgates of stem cell studies and treatment. Stem cells may be separated from fat tissues of the human body, and then re-introduced into the patient’s body to treat disorders such as arthritis, heart problems, autism, multiple sclerosis and Alzheimer’s. The treatment is often costly, maybe a few lakh rupees in India, and $5,000-$30,000 in the US.

In the recent past, the food and drug administration of the US wanted stem cell treatments to pass through “clinical trials” to get approvals, like other drugs and treatments. A historic hearing for the draft instructions for stem cell treatments in September 2016 was followed by a warning letter in August 2017, and seeking permanent injunctions from the federal court to stop some stem cell clinics from marketing products.

A pharmaceutical company needs to conduct a clinical trial and satisfy the regulatory body of the country concerned with the result in order to get permission to market a new drug. A clinical trial is experimentation involving a new drug in comparison with an existing one or a placebo, which is a treatment with no effect. The drug is eventually approved if it is proved to be more effective than the existing treatment (or placebo), and is also more or less safe.

A clinical trial, ideally having four phases of experimentation, might take a few years to complete. The cost might be millions of dollars, but offers a potential market of billions quite often. Phase I, usually carried out on human volunteers, tests for the safety of the drug, to determine the appropriate dose level for phase II.

Both safety and efficacy are tested on patients in phase II, and only the potentially safe drug doses are passed on to phase III, which is a full-scale evaluation of treatment effectiveness.

After phase III, if the company finds the drug dose to be fairly safe and effective, it submits the report containing details of the three phases, including statistical analyses, to the regulatory body of the country concerned. If the regulatory body is satisfied with the details, it allows the drug to be commercially manufactured.

The evaluation of long-term safety is possible only in phase IV, which is post-marketing surveillance and, ideally, can only be done afterwards. The first three phases—for which people must give their consent to be test subjects—may take a few years to complete.

Likewise, stem cell drugs are also under trial now. According to a 2016 article in Stem Cell Research & Therapy , about 1,000 clinical trials using stem cells have been performed globally to date, and more than 10 stem cell-based products have been approved in some countries.

The Indian stem cell industry is at a nascent stage. A 2012 study by Yes Bank and the Federation of Asian Biotech Associations forecast an annual growth rate of around 15%.

According to the “India Stem Cells Market Forecast and Opportunities, 2020” report, by the pharma and healthcare consultant Phamaion, the stem cells market in India is anticipated to grow at a compound annual rate of over 28% between 2015 and 2020 because of government and private investments, growing industry focus on stem cell research, rising awareness about stem cell banking, and evolution of new stem cell therapies.

A 2015 article in the Journal of Stem Cell Research and Therapy, projected the stem cell market in 2017 to around $16 billion.

Stringent regulations might curtail the growth rate initially, and clinical trials for the therapies will certainly need substantial time and money. However, safe and efficacious therapies will evolve more efficiently, and potentially unsafe and non-efficacious ones will vanish from the market. The desired ethical purpose would be served.

Atanu Biswas is professor of statistics at the Indian Statistical Institute, Kolkata.

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