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Clinical trials are heading east — again. Having experienced
the financial advantages of taking their trials into Central and Eastern
Europe, a growing number of major pharmaceutical companies and contract
research organisations are going further east — to India and China — to
tap into vast untreated populations of patients and even lower research
costs.
A 10-fold increase in clinical trial revenue is predicted for India over
the next five years and, with trial costs an estimated 40 per cent lower
in India than in the US, it is not hard to see why analysts at PricewaterhouseCoopers
and Frost & Sullivan have predicted a bright future for Asian research.
“It’s a challenging and exciting time at a clinical and a
regulatory level,” says Dhananjay Bakhle, head of medical and regulatory
affairs at Sanofi-Aventis in Mumbai, India. But he attributes the changes
under
way in India’s research community as much to the desire of Indian
companies to take home-grown molecules through clinical trials as for
multinational firms to bring studies to India.
Recent changes in patent and medicines legislation and the ongoing spread
of Good Clinical Practice (GCP) are having a major impact on India’s
R&D environment. The historical lack of patent protection for pharmaceuticals
in India helped national drug manufacturers to capture over 20 per cent
of the world generics market. But it also discouraged Indian companies
from investing in new chemical entity research.
Upsurge
However, new patent protection laws introduced across all industrial
sectors in April 2005 are encouraging a surge in innovative research
in India. A change to India’s Drugs and Cosmetics Act at the
beginning of 2005 has also been important in getting global companies
to consider India for their trials. Umakanta Sahoo, general manager
of Chiltern International, a contract research organisation in Mumbai,
explains that global companies could previously only get permission
to conduct clinical trials of new drugs in India, once equivalent phase
studies had been carried out elsewhere. “The change in the law
has removed the lag time that delayed the start of trials in India.
With the exception of phase I studies, which we still have to redo,
we can now perform clinical trials at the same time as they are being
done in other countries,” says Dr Sahoo.
Where India has the advantage over many other countries, he adds, is
in its speed of trial recruitment: “Fast recruitment is the key
to cost-effective global clinical trials and, because of the size of
our population, we can recruit at five to 10 times the rate of many other
countries,” explains Dr Sahoo.
Alongside the changes in patent and medicines laws is the surge in GCP.
Any academic centre or hospital unit that wants to take part in clinical
trials of new drugs will need to demonstrate GCP — something that
Dr Bakhle estimates only about 250 can currently do.
“At present, we have pockets of excellence, with pharmaceutical companies
going to the same people and the same hospitals each time to carry out
their studies. We now need to spread the load, and double the number
of GCP centres to 500, and then more,” he adds.
The Indian Forum for Good Clinical Practice (InFo-GCP) has been set up
to train more doctors in appropriate methodology and, by the end of this
year, the Drugs Controller General of India — the equivalent of
the UK Medicines and Healthcare products Regulatory Agency — will
take over the job of inspecting GCP-accredited centres involved in clinical
trials.
Dr Sahoo explains that most trials are carried out in public hospitals
rather than private ones because they are more likely to have the ethics
committees and laboratory facilities that are required for clinical trials.
“We have the same procedures and documentation for obtaining consent as
anywhere else, though obviously we have to take time explaining and translating
for patients. Some patients want to go back and think about it before
giving their consent, even though they have a lot of trust in the investigators,” Dr
Sahoo explains.
For those with concerns about the validity of clinical trial results
obtained in Asian populations for largely Caucasian patients, there is
also good news. Although there are differences in safety and efficacy
of a number of drugs, particularly in the cardiovascular area, Geoffrey
Tucker, head of the academic unit of clinical pharmacology at Sheffield
University, believes they are not insurmountable.
“There are genetic differences in pharmacokinetics, but they aren’t
all-or-nothing, and you can factor them into the design of the trial
and the analysis of the results,” he says.
He explains that pharmacokinetic differences are highly selective. For
example, the enzyme CYP2D6, which affects the metabolism of CNS drugs,
is absent in about 8 per cent of Caucasians, but less than 1 per cent
of those from Asia and Japan. So, for any given dose of drugs that need
CYP2D6, Asian and Japanese patients will be less likely to be deficient
in clearing it.
In contrast, 15 to 20 per cent of Japanese and Chinese patients are deficient
in CYP2C19, utilised by H2-blockers, compared with less than 3 per cent
of Caucasians, but such differences can be accommodated by dosage changes.
Advantages
“On the pharmacokinetics side, the advantages of being able to
carry out clinical trials in Asian populations probably outweigh any
disadvantages,
but we know less about differences in pharmacodynamics,” explains
Professor Tucker.
Ethnic differences in receptor type may have a more significant impact
on efficacy, he suggests, than pharmacokinetic variations. The issue
of ethnic variability in safety and efficacy is something that the ICH — the
International Conference on Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use — keeps under review.
But it is not currently seen as a significant impediment to global trials.
India is not the only country competing for global clinical trials business.
With its vast population resource and fast growing economy, China is
also predicted to become a major player. But language problems, added
to bureaucratic difficulties and limited availability of GCP may, for
the time being at least, leave India in pole position. |
The
Pharmaceutical Journal