The world and medical capabilities are advancing to tackle various diseases and illnesses. In recent years, scientists have developed numerous ways to find cure for complex diseases and develop medicine for them. To develop the right drug, scientists and doctors conduct clinical trials to test a new medical treatment, drug, device, or method on a group of people to examine how well it works.
In the pre-covid times, not many people were aware of clinical trials and their various aspects. Although, medical dramas like Grey’s Anatomy, House MD, and Good Doctor have done their bit to enhance medical vocabulary, thanks to COVID-19 the general public is now much more up-to-date with “placebo”, “early-phase” and “study sample.”
According to a report by Markets and Markets, the global clinical trial market in terms of revenue was estimated to be worth $38.7 billion in 2021 and is poised to reach $52 billion growing at a CAGR of 6.1 percent from 2021 to 2026.
According to the World Health Organization (WHO) report published in February last year, the United States of America had the highest total number of trials registered during 1999-2021 (157,618), followed by China (80,333) and Japan (57,754).
India’s position in the Clinical Trial Industry
After a halt in 2013, India is once again showing an upward trend in clinical trials. Industry experts told Financial Express.com that since India’s CDSCO implemented the 2019 New Drugs and Clinical Trials Rules (2019 new rules), the drug approval process has been faster.
These new changes has helped pharmaceutical companies to apply to the CDSCO for an expedited review process, waiving the requirement for local clinical trials in recognition of significant unmet medical needs, especially in cases of orphan drugs.
In 2021, India approved over 100 global clinical trials, the highest number since 2013. Covid-hit 2020 also saw 87 global clinical trials in India. These were 95 in 2019, 76 in 2018 and 71 in 2017.
According to the 2022 report by Research and Markets, the Indian clinical trials market size is expected to reach $3.88 billion by 2030. It is expected to expand at a CAGR of 8.2% from 2022 to 2030. However, there are still some persistent challenges.
“We have the standard data which says India has 20 per cent of the global disease burden. We also have probably 14-16 per cent of the global population. But we are only doing around 1.2 per cent of the whole global studies…If you look at even Indian companies, many of them in order for them to have more predictable timelines they also do their early clinical development outside of India. So, their typical destinations are Australia, the Netherlands, Europe, the United States, Malaysia, and Singapore, etc.,” Dr Sanish Davis, President, Indian Society for Clinical Research (ISCR), told Financial Express.com.
Dr. Davis is also the R&D Director of Janssen (J&J) Pharmaceuticals, India.
According to Dr. Davis, the unpredictable timelines in the drug regulation process in one of the biggest challenges in the clinical trial industry of India.
“…the government in 2023 budget has very clearly called out about incentivising R&D in India and there is a big push for R&D and if that has to happen there is also downstreaming ecosystem which has to help in that. Right now, many of these things are a little fragmented because you are not doing this like a regular feature and hence that ecosystem is fragmented or not well-developed,” he told Financial Express.com.
Meanwhile, Anirban Roy Chowdhury, Treasurer, Indian Society for Clinical Research (ISCR) maintained that as India has an unpredictable clinical trial ecosystem it loses out on participation and ultimately the country’s patients would have to wait for the drugs and care is delayed.
‘Skepticism over Early-Phase Trials in India’
According to a report by Grandview Research, in India, the phase III segment held the largest revenue share of over 50 per cent in 2021.
The industry experts opine that India is still trailing with respect to early-phase trial participation owing to restrictions against “non-India discovered molecules.”
“One of the key things which ail India to participate in early-phase development is that there is no drug discovery built as an ecosystem in India and there is a regulation that prohibits non-India discovered molecules to be tested for the very first time in India. This is one of the key roadblocks. When it comes to an Indian discovery, again in the case of an Indian discovered molecule, the cost of it and the experience which is supposed to be there within the country, that knowledge base for a new molecule may not be equitable. Basically, it may cost us much more to do it within India,” Dr. Seema Pai, General Secretary, ISCR told Financial Express.com.
Dr. Pai is also Director of Clinical Site Operations – India Cluster, GSSO, Clinical Development & Operations, Global Product Development, Pfizer Limited.
The report also revealed that the phase I segment is anticipated to register a significant growth rate of 9.9% over the forecast period owing to significant R&D investments by global as well local pharmaceutical and biotechnological firms.
The demand for new treatments and biologics in the country is further contributing to the growth of the segment, the report pointed out.
Impact of COVID-19 Pandemic on Clinical Trial Industry
Due to the coronavirus pandemic, pharmaceutical companies across the world faced logistical obstacles on the clinical trial industry. However, rapid and widespread adoption of the remote trial technique has significantly altered the traditional supply chain.
“One thing that the pandemic has actually taught us is more is collaboration. Every stakeholder collaborated and that actually expedited things. The regulators also stepped up. They were reviewing protocols till 11 in the night and although they were never used to doing virtual meetings…then they started approving protocols very fast. The ethics committee started reviewing quickly. This collaboration can be learned and implemented in other diseases,” Chowdhury told Financial Express.com.
It is noteworthy that direct-to-patient solutions were utilized to address the diverse logistical challenges of remote research and ecentralized trials facilitate sponsors’ access to a broad audience. Some experts also emphasised even though the pandemic has boosted the acceptance of these trials, there will be a significant demand for them even after COVID-19 is eradicated.
“It was a mixture of collaboration and awareness…People didn’t have to travel all the way to Delhi to get approval, ethics committee started meeting online which was again a very big difference compared to before. Telemedicine also helped a lot. There were also things like Direct-to-patient. So, rather than people coming to hospitals, people started getting their drugs at their homes. The clinical trial protocols have also changed globally to accommodate all these learnings from covid,” Dr. Pai told Financial Express.com.
Hesitancy Among People About Study Participation
There is still a lack of awareness about clinical trials and people often tend to believe that the participants of clinical trials are ‘guinea pigs.’ According to Dr. Pai, unlike West, clinical trial participation is not offered as a “care option” in India by physicians.
“…Clinical trials have to be offered by the treating physicians as a care option. In the west, typically what happens is, when a patient goes to a doctor apart from the routine medication they do offer the possibility of participation in a clinical trial. It is a fallback option when nothing else is available in the environment which is a roadblock,” Dr. Pai said.
Meanwhile, Dr. Davis emphasised that under the NDCT Rules, 2019, the central government is giving compensation and has also stated guidelines with respect to support system for the participants.
“If you look at the NDCT Rules which came out in 2019 that has kind of very clearly stated what are the support systems that the patients will have if they participate in the study for example things like compensation. India is probably one of those unique countries in the world where patients are actually compensated in case they have a clinical trial injury…the government has taken that very clear step that patients have to be compensated if they have an injury during the study and that is in the form of both medical management of their illness if it worsens as well as compensation in case there is a serious adverse event like death. So, that’s a huge safety net for participants in the study,” he told Financial Express.com.
Futhermore, Chowdhury also pointed that patients should be aware of all treatment options including clinical trials for prospective treatments.
‘Need for Real-World Evidence and Real-World Data’
In January 31, 2023 report, United States Food & Drugs Administration (USFDA) said in a statement that it uses Real-world data (RWD) and real-world evidence (RWE) to monitor postmarket safety and adverse events and to make regulatory decisions.
According to USFDA, Real-world evidence is the clinical evidence regarding the usage and potential benefits or risks of a medical product derived from analysis of RWD which is the data relating to patient health status and/or the delivery of health care routinely collected from a variety of sources like Electronic health records (EHRs), and data gathered from other sources that can inform on health status, such as mobile devices.
Chowdhury emphasised that in a clinical trial is a controlled environment but the drug is used in an uncontrolled environment.
“…So, generating data when that drug is actually being used in an uncontrolled environment is also important because it actually gives the real effectiveness of the product…with respect to this India still does not have guidelines around it,” he added. To this, Dr. Davis added that drug discovery is an area where artificial intelligence has huge potential.
According to experts, using Real-world evidence can help researchers in understanding how new therapies work for everyone who requires them, including those who do not take part in clinical trials.
‘Covid-like approach for other diseases: Is it possible?’
According to Chowdhury, global collaborations among various stakeholders played a crucial role in combating the coronavirus pandemic.
“Every stakeholder collaborated and that actually expedited things. The regulators also stepped up. They were reviewing protocols till 11 in the night and although they were never used to doing virtual meetings…then they started approving protocols very fast. The ethics committee started reviewing quickly. This collaboration can be learned and implemented in other diseases,” he told Financial Express.com.
Dr. Davis explained that although a similar approach and collaboration is possible for finding cures and treatments for diseases like Alzheimer’s and Parkinson’s but it is important to understand that the research to understand the causal factors take time.
“If you take diseases like say cancer…this is one place where academia, industy, regulatory agencies and all the other stakeholders work in a very “hyper” state and the reason for that is…earlier cancer used to be like…if you can control it…in today’s time its more like going towards cure and the patients can’t wait. So, that’s why a huge amount of collaboration is happening in the field of oncology because everyone understands that this can be a game-changer. Now when you come to diseases like Alzheimer’s or Parkinson’s…it’s not just one mechanism that is at fault here…there are several different mechanism which are going wrong…the disease pathogen is still being understood. So, I think eventually the same approach that you have for oncology and rare diseases, etc. will be possible in these areas too,” he told Financial Express.com.
Meanwhile, Dr. Pai added that, unlike neurological disorders like Alzheimer’s, in oncology or rare diseases, the treatments are targeted.
‘Multiple Global Regulators, Multiple Rules’
Under the 2019 new rules, applicants may apply to the licensing authority for an expedited review process in which the evidence of clinical safety and efficacy has been established even if the drug has not completed all the normal clinical phases.
One of the provisions that may pose a challenge for some biopharmaceutical companies is that the companies must commit to conducting postmarket, phase 4 trials to evaluate the long-term effects of the approved product. Another factor that serves as an roadblock is that even if a molecule is approved by USFDA or EMA, the companies are still required to do some additional experiments.
“…Although there are variations in population and genetics but at the same time when it comes to data packages the acceptability of these data packages across agencies is something that is truly a wishlist of every pharma company in India. The checklist for regulations was probably made many years ago when science had not evolved the way it has evolved today. So, the targets which we are looking at today are very different…so there are several experiments which will not be required to be done in the new age but when we go back to our regulator to do those experiments and come back which again puts India at a huge disadvantage…this is only India specific and no company is going to these things, especially for India,” Dr. Pai told Financial Express.com.
Moreover, Chowdhury told Financial Express.com that India is still not a member of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and the Pharmaceutical Inspection Co-operation Scheme (PIC/S).
“EU, US and Japan basically came together saying that any study done following ICH principle would be mutually acceptable and India still is an observer, not a member. We keep talking to the government and recommend taking up the membership. Once India becomes an ICH country this will get streamlined,” he added.
It is noteworthy that ICH membership will help Indian pharma companies to achieve global quality standards and it will also decrease repeated inspections by regulators.
In March 2020, there were reports that India will soon become a full member of the ICH. However, it has not announced the membership yet. In February 2016, India’s Central Drugs Standard Control Organization (CDSCO) joined the council as an observer so it currently has no voting rights although it can attend ICH meetings and nominate experts to working groups.
The organization currently has 16 members and 32 observers. ICH’s founding members include the European Commission, the FDA and Japan’s Pharmaceuticals and Medical Devices Agency.
‘What more needs to be done?’
According to Dr. Pai, the mode of data generation has changed with covid.
“Now, the data is being transferred in a very quick manner through cloud servers. Whatever is collected… is logged in into an e-device and that is put into a cloud server and the final data comes to the pharma company immediately. So, earlier, let’s we were taking 6-7 years to complete a trial…this has now significantly accelerated and we can now bring it down to 3-4 years. So, ultimately the drugs come to the patients in a much faster way,” she told Financial Express.com.
She highlighted that although many of the recent trends from the global clinical trial industry is being adopted in India, there is also a need to focus to capacity-building.
“..it is important to understand that how many home-health nurses we have in the country who understand clinical trials as much as nurses in the West. So, that capability and capacity building is critical. Currently, we are focusing on the regulator or the doctor…and we are not looking at the middle ecosystem…In many countries, these measures are a part of standard practice,” Dr. Pai added.
The experts also pointed out that countries like Australia pose a conducive environment for clinical research.
“…in Australia…any company can go there and take an ethic committee…there is a process for that…but as long as they have an ethics approval there is a tacit understanding with the Australian agency to go forward with the trial. Second thing is that the early phase development has taken so much of steam over there that every doctor who is a practicing doctor is also able to do a phase 1 clinical trial. They also have early-phase units within the hospitals which is what makes them very attractive,” Dr. Pai said.
She also said the government is building NIPERs and AIIMS across the country.
“These are the things that came after COVID which the government realised that there is an imminent need for country-specific drug discovery to happen,” she added.
Dr. Davis emphasised that the clinical research industry needs recognition in the current scheme of R&D incentivisation.
“Clinical trials are going to be the enabler of the R&D push that the government wants. How that will actually in the rest of the ecosystem is also going to be important from that recognition. Having a predictable regulatory regime is also important. The capacity building has to happen both at the regulatory offices and Subject Expert Committee which are reviewing projects,” he added.
