A proper monitoring system has to be in place while conducting the phase-1 clinical trial of a medicine or an Investigational Medicinal Product. Similarly, active involvement of the Ethics Committee should also be ensured during the trial period, said Dr Vasantha Muthuswami, former senior deputy director general & scientist at the Indian Council of Medical Research (ICMR).

Speaking on 'Special Issues in Phase-I Clinical Trials', in a workshop organized by DIA-India, Tamil Nadu Chapter, she said that the role of investigators has to be watched carefully as the investigator is responsible for ensuring proper and ethical conduct of the clinical trial at the site. As per the Guidelines for phase-1 Clinical Trials, the investigator must assess the health of trial subjects throughout the trial and should withdraw any subject whose life is at risk.

Dr Muthuswami said that there are so many cases where established medicines as well as IMPs had the potential to harm subjects in phase-1 trials. Regarding the safety aspects she said reviews of safety of phase-1 show that it has a good safety record. Overall, the incidence of serious adverse events related to the IMP was about 0.02 per cent. However, some healthy subjects have also died in certain trials.

She quoted some incidents that a man had died of cardiac arrest after taking an IMP in a trial in Ireland in 1984. In another case she said, a woman died after receiving a high dose of lidocaine - a widely used local aesthetic to prevent discomfort from endoscopy, in a trial in USA in 1996. She was discharged soon after the procedure and died at home.

Further she said a woman with mild asthma died of lung damage after inhaling hexamethonium in a trial in USA in 2001. She added that hexamethonium was an old medicine, which was administered by injection to treat conditions other than asthma, and is now rarely used.

Dr Muthuswami has however said that the phase-1 trials can identify IMPs with potential for success as well as exclude failures, and thereby prevent unnecessary exposure of the IMPs to many more subjects. Phase I clinical trials involve the first ever exposure of a prospective drug to humans.

In the workshop, among others, members of DIA-India Tamil Nadu Chapter, Dr Annabelle Rajasekaran, Dr Mohana Sundaram and Dr Balasubrahmaniam were present. Attendees included doctors of various hospitals in the city, students of pharmacy colleges, industry professionals, CROs and other service providers.