Indian contract research organisations (CROs) are facing an identity crisis. They are struggling to restore their image as charges of illegal clinical trails are doing the rounds. The recent deaths of 49 infants during clinical trials at the All Indian Institute of Medical Sciences (AIIMS) had the potential to snowball into a major controversy and severely damage the chances of Indian CROs eying the $20-billion global clinical trials market opportunity.

Let us also not forget the often published reports of illegal clinical trials conducted in the country?especially in the southern states of Karnataka, Andhra Pradesh, Tamil Nadu and Kerala?for the treatment of oral and breast cancer, diabetes, diarrhea, malaria and cardiac disorders.

As dusk settles down over the AIIMS incident with an internal inquiry suggesting that the deaths were not due to medicines used in the clinical trials, but because of the diseases that the children were suffering from, clinical trials players?global and domestic?are breathing a sigh of relief. A sword, however, still hangs on their head as a final report from the committee appointed by the health ministry is awaited.

For now, it?s back to business for the 120-odd clinical trials players comprising the $300-million domestic clinical trials market?expected to reach $2 billion by 2010, with 200 players in the arena. At the same time, the domestic clinical trials industry is working hard to spread the message that the trials conducted in the country are subject to intense scrutiny, written and informed consent from the patients undergoing trials is mandated and that there is no hanky-panky involved.

In the prevailing scenario, advocacy of the good practices adopted by the domestic clinical trials players augurs well for the overall growth of industry. ?No clinical trials player in India does any unethical work. Or else, we?ll be out of business. The overwhelming majority of trials are conducted in a legal framework,? insists Brijesh Regal, CEO of Apothecaries Clinical Research, a New Delhi-based clinical trials company.

?While the issue of illegal clinical trials is definitely an area of concern, many of the incidents reported indicate ignorance rather than deliberate malafide intensions,? informs a senior Drug Controller General of India (DCGI) official, monitoring trials in the country.

Clinical trials are done in a sample representative population and under determined guidelines for diagnostic and therapeutic interventions. They involve all stakeholders in the healthcare system, says IS Gandhi, medical director, Vimta Labs. ?Clinical trials are often the only means of hope for patients with several life threatening diseases that have no known definitive cure,? informs Arvind Lal, chairman and managing director of Dr Lal Pathlabs. ?Increasing globalisation has brought about fundamental changes in the way clinical trials are conducted here,? he adds.

The total number of patients undergoing clinical trials in the country is close to 20,000, claim industry sources. The clinical trials legislative requirements are guided by specifications of schedule Y of the Drugs and Cosmetics Act in India. The government has also taken the initiative for establishing quality requirements by setting up the National Board for Accreditation of Testing and Calibration Laboratories (NABL) for clinical and diagnostic laboratories.

?We have to be prepared to give quality leadership and come up to global standards in the clinical trials space,? says Lal. ?This can happen when we have good infrastructure like world-class laboratories for doing safety testing to find out for any toxicity in the drugs under development,? he adds.

According to clinicaltrials.gov, the US continues to be the most favoured destination for clinical trials. Over 57 % of all global trials are being conducted in this country. China has again overtaken India in the number of trials conducted in the country. There are currently 419 clinical trials ongoing in China against 376 in India.

?India does not participate in phase I trials, the most risky of all trials. The overwhelming majority of trials conducted in India are phase II and III. By this time, the drug has already been tested in humans abroad and has been found to be safe,? says Anand Bidarkar, vice-president (business development), SIRO Clinpharm.

Nevertheless, it is imperative to know how clinical trials are undertaken here. Unlike in the west, CROs conduct only 35?40% of clinical trials in India. The rest of the trials are directly carried out by the pharmaceutical companies themselves or are initiated by doctors. Many multinational companies like Pfizer, Novartis have their own clinical trial staff, so do major Indian pharma and biotech majors like Ranbaxy and Panacea Biotech.

In addition, Indian laws require any trial conducted in India by a CRO to go through three levels of scrutiny. The first level is the medical department of the CRO that reviews the protocol and decides whether it is feasible and ethical to conduct the study in India.

The second level of screening is the DCGI. It reviews the protocol and evaluates whether the study proposal is backed by sufficient safety data or not, the ethical implications of the trial, if the trial is being conducted only in India or other developed countries as well and only after a rigorous analysis provides approval to the study.

The next and often parallel level of screening is conducted by the ethics committees or the review boards of the hospitals that conduct the trial. These committees consist of the representatives of the general public and medical professionals and the doctor who will conduct the trial has to satisfy the committee about the need and appropriateness of the trial. No trial is ever started unless the three checks are completed.

For trials conducted directly by the pharmaceutical companies and doctors, there are usually only two levels of scrutiny. Hence the trials conducted by CROs have an additional check built in over those conducted directly. Also, because CROs conduct a number of studies for different companies, their staff gains the expertise to point out potential problems even before the trial starts. This is another factor adding to the safety of trials carried out by CROs. This is the reason why many smaller companies decide to approach CROs when they lack expertise.

All CRO staff in India is trained in globally accepted GCP guidelines, claims Bidarkar. These guidelines lay down stringent procedures to be followed in dealing with patients and have clear rules to deal with illiterate patients to ensure that they are fully aware of risks if any and not exploited.

After a trial starts, it is subjected to an intense level of monitoring. All the doctors participating in the trial have to follow strict guidelines for reporting any health problem in the trial participant whether related or unrelated to the trial. There are round-the-clock helplines to help the doctors. Trials conducted by CROs are audited internally, as well as by third party external auditors. This is another built-in check mechanism to ensure responsible conduct of clinical trials. The USFDA has reportedly inspected Indian clinical trial conduct at sites and has found them to be acceptable. ?All the data generated in India must meet USFDA requirements or those of drug regulators from other countries,? insists Regal.

But are clinical trials necessary? ?Globally, clinical trials are a necessity for the ultimate benefit of mankind. How can one have better drugs with no prior trials,? questions Lal of Dr Lal Pathlabs. Besides, it would be dangerous if drugs tested only on western population are introduced in India directly; there could be important differences in the usage and dosage required. Hence trials need to done on Indian patients as well.

?We should remember that almost all allopathic drugs used in India are of foreign origin. There is hardly any original drug worth mentioning that has been developed by an Indian pharma company. Hence, there is no reason to feel threatened if any foreign company drugs are being used in clinical trials in India,? says Bidarkar.

The roadmap therefore is crystal clear: At a time when clinical trials in India are poised for a major growth, the onus is on the industry to cut out the negative sentiment.

?With inputs from BV Mahalakshmi