If you want to know your past, look into your present conditions. If you want to know your future, look into your present actions." - Chinese Proverb
In India, since 2005, when IPR laws and Schedule Y were amended, there has been a lot of buzz around clinical trial industry. The country has been labelled as a new "hub" for clinical trials. The market growth estimates have been very optimistic ranging from 30-50 per cent per annum. Although the original McKinsey estimates of market size of US$ 1.5-2 bn for 2010 have not been achieved, the financial analysts are projecting US$ 3 bn by 2015. The current market estimates are around US$ 300 mn. If the 2015 estimate is to be achieved, the market has to grow at a compound annual growth rate (CAGR) of 58 per cent! The question is: is this a hype or reality? To answer this question, it would be necessary to look at Indian clinical trials milieu and the clinical trial data.
Global clinical trials scenario
One of the most reliable sources for global trials is the US registry clinicaltrial.gov. Since 2005, all companies register all trials in the registry. The total number of trials registered has increased from 10,480 in 2005 to 11173 in 2009 (Table 1). The number dipped in 2006 and rose for 2 years, and fell again in 2009 by 3.1 per cent. The 2005-9 CAGR is very small 1.6 per cent.
Asian scenario
In India, the total number of trials in 2005 was 137 which increased to 246 in 2009. The number of trials in 2009 was 9.6 per cent lower than in 2008. The CAGR was 15.8 per cent. However, as per CDSCO data released in Aug 2010, the number of global trials approved in India has remained more or less constant. The numbers are: 2007 259; 2008 246; 2009 258.
In contrast, China and Korea showed a higher CAGR of 27.7per cent and 36.8 per cent respectively. Also, the 2009 number of trials in China and Korea was higher than 2008 number by 15-20 per cent.
Industry trials
Of the total trials, the industry trials contribute around 55-60 per cent. The number of trials registered by industry was 6485 in 2005 and was 6409 in 2009. The number in 2009 was 8.9 per cent lower than in 2008. The 2005-9 CAGR is negative (-1.5 per cent) due to a dip of 8.9 per cent in 2009. The CAGR 2005-8 was 1.13 per cent.
Asian scenario
The total number of trials in India in 2005 was 101 which increased to 195 in 2009. The CAGR was 17.9 per cent. For both India and China, the number in 2009 was lower than in 2009. This could be an effect of recession. The 2005-8 CAGR for India was 29.6 per cent and for China was 23.2 per cent. In contrast, the CAGR for trials in Korea was highest CAGR at 22.9 per cent. Also, there was no reduction in Korean trials in 2009. This could be cause of Korea's well developed clinical trial infrastructure, accredited investigators and favourable regulatory environment.
Distribution of trials by phases
Globally number of Phase I trials shows highest growth - CAGR of 21.3 per cent. In contrast, Phase III trials had the lowest CAGR - 9.3 per cent. The Industry trials showed a similar pattern with a lower CAGR of -11.8 per cent. The number of phase III trials has been declining every year from 2005 to 2009. For India, Phase III trials show the lowest CAGR.
Compared to 2008, there was a reduction of Phase III clinical trials for industry by 25 per cent and for India by 34.6 per cent. The numbers were: 2008 Industry 1082 India 136; 2009 Industry 823 India 89.
According to CenterWatch, study starts since the third quarter of 2008 have declined by nearly 40 per cent. The global CRO market, which was growing at an annual rate of 15 per cent, was expected to slow down to 8-9 per cent growth in 2009. Pharma companies aggressive merger and acquisition spree pushed them to cut costs, whilst the tight credit and equity markets have caused biotechs to delay or cancel projects to conserve cash.
The proportion of industry trials in 2009 was: Phase I 32.5 per cent; Phase II 32.6 per cent; Phase III 21.4 per cent and Phase IV 13.5 per cent.
For India the proportion was: Phase I 12.8 per cent; Phase II 27.7 per cent; Phase III 45.6 per cent and Phase IV 13.8 per cent.
The higher proportion (65 per cent) of trials in Phase I and II suggests that Industry is focusing on early clinical development. In contrast, India has more trials (59 per cent) in Phase III and IV. In India, Phase I trial number is expected to be lower because of regulatory embargo on Phase I for drugs discovered outside India. Also, India does not have sites ready for early Phase II - proof-of-concept (POC) trials. These trials require clinical sites which have facility of admitting patients in hospital in a unit where multiple pharmacodynamic, pharmacokinetic and safety measurements all feasible. Hence, it difficult to organize POC trials in India.
Regulatory situation
In 2006, there was an effort to streamline regulatory process for clinical trials to give time- bound approvals within six to eight weeks for global trials approved in category A countries. However, the categorization is removed. Also, six to eight weeks is the time for first response from CDSCO. The response could be approval, rejection or a deficiency letter. From Sep 1-13, out of 43 letters issued for global clinical trial, 22 were approval and 21 were deficiency letters. The regulatory clock stops once the company gets a deficiency letter. After the company responds to the queries, it will take six to eight weeks to get CDSCO response. Earlier, the import license was issued simultaneously with the trial approval. Now it is issued two weeks after approval. Hence, the overall time to obtain clinical trial approval and import license could be 16-18 weeks. The uncertainty and delay in approval process impacts India's potential of completing the trials faster than in the West.
For small/medium biotechs the strategy of conducting complete trial in India, offered tremendous time and cost saving. However, CDSCO does not approve India only trials. Usually <50 per cent of global number of patients are permitted in India. This makes India a less attractive option for small/medium biotechs.
In the wake of Bhopal gas tragedy judgement, the government's focus has come to clinical trials conducted at Bhopal and other cities in MP. The government is seeking information regarding all ongoing and past trials from all the MP hospitals, the investigators and the pharma companies/CROs. This has scared the investigators and made them withdraw from all clinical trials. This situation is not healthy for encouraging physicians to become investigators.
Reporting by media
Indian media has an important role in shaping public perceptions about the clinical trials. Since the time India became an active participant in the global trials, the media has flashed many alarming stories on clinical trial conduct. The titles of most reports focus on death of clinical trial subjects. All the stories are negative usually painting the government and industry in black. The stories create a feeling that a) India does not have adequate regulations to control industry activities, b) the government is lax and c) the international companies are always flouting the ethical, regulatory and scientific norms. The reporting has been selective focusing on global trials. So far, there are very few reports on Indian company trials. The media expose has led to government setting up inquiry committees. The inquiry findings are not discussed or highlighted in press. AIIMS received a lot of bad press for the trials in children.
But the fact that inquiry committee gave a clean chit to AIIMS investigators, did not get much coverage in the press. The overall impact of the media coverage has been negative for India's image as a good destination for trials. This has made the international Big Pharma and small/medium biotechs reconsider their strategy of placing clinical trials in India.
Future scenario
Although there is optimism about growth in CR industry, the reality is still a cause for concern. As per Scrip Clinical Research June 2010 issue, the growth was sluggish for CROs in the first quarter of 2010. In 2009, many pharma companies delayed or cancelled the projects, leading to fall in CRO revenues.
The number of Industry trials registered on clinicaltrials.gov between Jan-June 2010 was seven per cent less than in Jan - June 2009. For India the reduction was 16 per cent.
Although it would be easy to pass of reduction in Indian trials as a recession effect, the higher reduction in 2009 number of India trials of 34.6 per cent compared industry average of 25 per cent, might suggest impact of the regulatory restrictions and negative media stories
The industry is optimistic that the recession effect will wear of over time. But it is not sure whether the regulatory and media scenario will improve. The future of the Indian clinical trials industry is likely to shaped by the local factors - regulatory restrictions and media - rather than global factors!
The author is President, Clininvent Research Pvt Ltd