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Back on Track

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After a lull, the Indian clinical trial industry is likely to witness progress, due to a slew of regulatory measures adopted by the government. However, a lot needs to be done to position India a clinical trial hubs By Usha Sharma

Recent years have seen a slowdown of clinical trials in India in the wake of stringent directives from the Supreme Court asking the government and regulatory agencies to take measures to ensure safety of patients participating in clinical trials of new medicines.

Over the last year and a half, the Ministry of Health and Family Welfare has taken various steps to address the challenges posed by regulatory uncertainty. Regulations were amended and further guidance was given on existing ones.

India accounts 17 per cent of the global population and 20 per cent of the global disease burden but still accounts for a significantly low number of clinical-trials.

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Suneela Thatte

Suneela Thatte, President, Indian Society for Clinical Research (ISCR) informs, “For a country that has the second highest population in the world and the highest burden of disease, around 1.4 per cent of global clinical trials takes place in India (https://clinicaltrials. gov/ct2/search/map?map=SS). That in itself is indicative of how under represented India is in terms of clinical research. Besides a high patient population and a significant representation of diseases characteristics of both developing and developed economies, India also has well qualified English speaking investigators and good infrastructure. So, we have all the requisite requirements needed for clinical research.”

However, market reports explain that the situation was not so unfavourable for the Indian clinical research industry till 2010 from between 2004-10, many multinational and domestic pharmaceutical companies choose India as the preferred destination for conducting clinical trials. Then why did the situation turned so bad?

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Kamal Shahani

Kamal Shahani, MD, Clinminds explains, “New regulatory framework and changes took a long time. This made leading global pharma companies feel uncomfortable as the cost escalated due to the flong waiting period, ultimately resulting in delay of global studies. Once companies leave any market, it is difficult for them to come back with new projects.”

So how badly was the clinical trial industry in India hit? Is it picking up now?

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Apurva Shah

Apurva Shah, Founder and Group MD, Veeda Clinical Research apprises, “All the trials of new molecules are moving at a slow pace due to bureaucratic delays of the Subject Expert committee (SECs, formally known as New Drugs Advisory Committees). There is still a lack of clearly defined role for them and meetings are conducted at less frequency.” The frequency of their meetings as not sufficient.

Rebuilding trust

Undefined regulation over the past few years have forced companies to conduct many clinical trials to move outside India which has impacted the industry’s growth largely. What efforts should be taken into consideration to re-gain the position and build a trust under global business market?

Shahani suggests, “We need to provide a stable and predictable regulatory environment to multinational companies. This will be the most important step to win back the confidence.”

Advocating a more patient approach, Thatte says, “We cannot expect a dramatic reversal in the near term as the clinical research life cycle is a long drawn out one. In addition, rebuilding trust and confidence of global stakeholders in conducting clinical research in India is a long and slow process. We will probably see normalcy restored in 2017-2018. What is important and reassuring, however, is that stakeholders are now beginning to re-look at India to place clinical trials.”

Two prominent steps taken by the government, clinical trial compensation formula and mandatory audio video (AV) recording of the informed consent process provides some hope and stability to the industry.

Clinical trial compensation formula

The government has already taken a few steps to give relief to the industry and announced compensation guidelines and mandatory audio video recording of the informed consent process. In December 2014, amendments were made to the Indian compensation guidelines by the regulators via a Gazette Notification No. GSR 889 (E) which became effective in June 2015. Many of the contentious clauses of the Rule 122 DAB of the Drugs and Cosmetics Act (released in January 2013) on compensation were addressed, making the regulation balanced and less prone to misuse and litigation. The revised guidelines rationalised compensation and medical management for injuries caused during and due to participation in clinical research, thereby balancing the interests of the patients and pharma innovators, while at the same time bringing clarity in the process.

Thatte informs, “For the first time in the world, formula have been introduced by the regulators for calculating the financial compensation based on no–fault principle. This not only provides ease of implementation and consistency but also helps the sponsor of the trial to understand the maximum possible liability and plan appropriately while protecting the patient well being.”

Shahani argues saying, “Compensation guidelines are now clear, and reduces the ambiguity. Also, recent changes in  mandatory audio video recording would help it further.”

Mandatory AV recording

With regards to mandatory audio visual (AV) recording, via a Gazette Notification dated July 31, 2015, the Ministry of Health and Family Welfare made amendments in the Drugs & Cosmetics Rules, 1945, to provide clarity on the nature of clinical trials where the informed consent process needed to be audio-visually recorded. Such recording is now necessary only for vulnerable patients and for trials involving new medicinal entities.

Thatte informs, “The regulators have been requested to issue a clarification on which patients will be deemed ‘vulnerable’ and what will qualify as ‘new medicinal entity’, so that there is no ambiguity in this regard. We expect this clarification in the near future.”

Shah while expressing  his views on mandatory steps on this aspect says, “In the current scenario, priority is to reassure the government and community at large about the standards adopted by the industry. AV recording is a positive step ahead to build trust and confidence in  clinical research industry in India.”

Exploring opportunities

So will all these efforts help the industry move forward?

Regulatory reforms have started showing positive outcomes and the industry is slowly regaining its position. Shah informs, “There has been a rise in clinical trial activities. Various types of trials have different levels of risk and expertise and therefore have varied growth in India. Regulators have realised that they have to be differentiated and cannot be just put in one basket of clinical trials.”

He continues, “The BA/BE trials of old drugs on healthy volunteers has grown steadily due to the fact that the risk levels are very low. This is the strongest segment in India in terms of expertise and volume. However, the patient trials for generics are not growing at the same pace due to the lack of full understanding from the regulators of the changing needs of the industry. This is the new wave of drugs and we need to move fast to build expertise here. The risk level is relatively very low considering these are single dose trials of old drugs.”

Shah further elaborates, “The trials of biosimilars isn’t growing fast enough and this is a very bad thing. The segment is very promising and India cannot afford to lose the opportunity to gain a strong foothold in it. Being strong in this segment, will deliver a lot of social benefits because it can provide cheaper alternatives to very expensive international products for our population. I hope that all the stakeholders, right from the government to the volunteers, have realised that the world of research isn’t going to stop for India. If India wants to play a role in this industry (which is very important for us due to the huge disease burden which needs economical treatment), we need to attract clinical trials to our country. Price is not an attraction for the industry but reliability of data and predictability of timelines are the most important factors. We still have most of the ingredients that we had before to become an important centre for drug research and development.”

Shahani says, “For a country like India, it is important to have access to new drugs. This would require quicker regulatory approval process, both for clinical trials and marketing authorisation. The clinical trial application (CTA) approval process should be faster and transparent. At present, CTA approval time frame is lengthy and unpredictable. Apex committee meetings should take place on a regular basis. Changes like accreditation of sites, investigators and ethics committees should be implemented on a priority basis to end the uncertainties.”

Collaborative approach

According to the data available clinicaltrials.gov (as on 11/03/2015), 1.4 per cent of global clinical trials are currently carried out in India compared with 3.2 per cent in China, 1.5 per cent in the Czech Republic, 1 per cent in Turkey and 0.9 per cent in Thailand. Half of all the trials being conducted worldwide are based in North America, with the UK hosting 5.5 per cent of the trials.

Shahani suggests the growth prospect for the Indian clinical industry and says, “We need to reduce regulatory approval timelines. The government should constantly interact with the industry and other stakeholders to create a better dialogue-based environment  We need to ensure that we provide a stable and predictable regulatory environment to pharma companies to encourage them to grow their investments in India.”

Thatte too opines, “Regaining trust and confidence is a long and slow process. It is the responsibility of all stakeholders to work collectively to ensure that we bring clinical trials back to India.”

Lessons learned

A well constituted regulatory framework becomes a sign of stability and reliability to any country. However, the undefined regulatory framework of clinical trials industry had led to drop. Commenting on the key learning from the mistakes, Thatte says, “A considerable drop in clinical research in India from 2013-2015 was therefore largely due to the uncertainty and unpredictability in the regulatory environment. The biggest learning for India that we need to have a clinical research agenda of our own and that regulations and guidelines should be determined with a focus on research, science and good governance and should not have knee jerk responses to judicial and social activism.”

Shah adds, “One-sided negative publicity due to ignorance of right procedures and systems can cause a lot of damage and therefore open communication and transparency from the industry will help to neutralise some of it. The ethical and social angle is very strong for our industry and therefore it is very important for all the stakeholders to understand it well.”

Moving ahead

All the stakeholders of the Indian clinical trial industry seem optimistic about steps taken by the regulators. Frost & Sullivan estimates that the Indian clinical trial market was expected to achieve a double digit growth year-on-year (YoY) starting from 2008 till 2016. Since the number of clinical trials in India have dropped,  the possibilities of understanding and evaluation process of each clinical trial are likely to go up and ongoing trials may go through tough process. The issue has become so sensitive that even the Supreme Court of India has stripped the DCG(I) of its powers to approve clinical trials as now there is a three-tier system for all trials. There is a subject committee of 10-12 members for each therapeutic area, a technical committee, which has 20 members, and an apex committee. The application reaches the DCG(I) only after approval from all three tiers.

Commenting on the move towards more rational guidelines, Thatte says, “The strengthening of the regulatory-ethical-operational framework for conducting clinical research in India has led to an ongoing process of streamlining and stability and we have seen several new orders and guidelines introduced over the last year.”

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Due to a lack of streamlined regulations, the industry has already suffered a lot. However, India with a large pool of patients and disease profiles, the clinical research industry has an immense potential to grow. Today, the regulators have realised the need of streamlining regulatory process for making the Indian clinical trial industry an organised sector.

Shahani mentions, “Though it was good to learn from our own mistakes and find our own solutions, we could have adopted the internationally accepted best practices from the regulated matured markets of the US and Europe. Regulatory approval process needs to change. The process is still extremely slow and complex in comparison to other markets, and this discourages major pharma companies.”

Shah expresses his concerns on the market which the country has lost due to undefined regulatory framework. He says, “We have lost a huge market share to several Asian countries. These countries have grown at the expense of India.” He suggests, “We need to win back the confidence of the key global players.”

An uphill task

There is a still a long way to go for the Indian clinical trial industry. How can companies pursue this opportunity and win the confidence of global pharma players to bring clinical trials to India especially when the country (India) has such a vast patient pool and resources?

In reply to  this, Thatte replies, “I would like to quote from a recent interview with the DCG(I) where he says, “I can tell you with certainty that India is ready to do extremely good work in clinical trials now. We have created a platform through which India will become a preferred destination for clinical trials. In the next eight to 10 years our contribution to the global clinical trial industry should be at least 10 per cent. That’s the plan. This will create a huge job opportunity. It will also result in huge skilled manpower for drug discovery research, where exactly India’s true strengths lie.”

She feels that, “This is a very encouraging statement coming as it is from our regulatory authorities and we are confident that we now have a more robust regulatory framework and a government committed to bring clinical research back on track in India. Clinical research in our country is a health imperative and important to the progress of the health of our people and the economy. We need a robust, regulatory framework that ensures that clinical research is conducted in a fair and transparent manner, safeguarding the interests of patients while keeping in line with the basic tenets of science.”

Shahani believes that India has the potential to attract global clinical trials to India. He informs, “India has a talent pool of qualified and experienced medical professionals and scientists, diverse patient pool, globally competitive infrastructure, certain cost advantages and presence of all key global pharma companies. This makes India an attractive destination for clinical trials.”

While signing off, Shah mentions, in response to Indian Prime Minister Narendra Modi’s plan to make it easier to do business in India, the health ministry proposed pre-submission meetings in a bid to enable technical deliberations between stakeholders and  drug regulators. The meetings will take place before drug companies make a formal application for clinical trials. The move is expected to enhance efficiency in the sector, given its muted growth over the past two years, and increase transparency, predictability and accountability.

Following the right steps will signal a healthier and transparent business environment for conducting clinical trials in India. It may not immediately get reflected on paper but things seem to be headed in the right direction finally.

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