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