CLINICAL TRIAL 038; ERROR

Phase II: The drug that has cleared Phase I tests is administered to a group of approximately 100-500 informed patients to determine its effect and also to check for any unacceptable side effects. These subjects are people who have the disease/condition for which the drug is being developed. The purpose is to determine the drug8217;s dosage range and clinical effectiveness in its targeted population. Here, patients with the disease under investigation are studied. Typically these trials are placebo-controlled. That is, one group is administered a placebo inert compound that is formulated to simulate the test drug in physical appearance while the other group of patients is given the test drug. The investigators who conduct phase 2 trials are usually experts in the disease being studied and /or in the evaluation of the drug8217;s effects on the disease process.

Phase III: In this phase, a group of 1,000-5,000 is studied for the company to use statistics to analyse the results. If the results are favourable, the data is presented to the licensing authorities for a commercial licence. Phase 3 clinical trials are well-controlled studies in which the effectiveness of the drug is tested in conditions similar to its potential market. This phase involves thousands of patients with a targeted disease. However, it is possible that some adverse effects of the drug may be missed even at this juncture, only to surface after the drug has been marketed. The data obtained in phase 1,2, and 3 trials are used to prepare documentation for regulatory approvals. Only about 8 per cent of drugs approved for development are eventually approved for marketing. Women of child-bearing age, very small children and the elderly are generally excluded from the majority of phase 2 and 3 clinical trials.

Phase IV: This is a surveillance operation phase after the medicine is made available to doctors, who start prescribing it. The effects are monitored on thousands of patients to help identify any unforeseen side effects. Out of thousands of compounds synthesised and screened, only 10-20 per year undergo pre-clinical testing, and only 5-10 enter phase 1 trials. Only about 1 out of every 15 drug candidates entering development actually receive regulatory approval

THE ETHICS:
An Independent Ethics Committee permits the trial to be conducted at a particular institute. A monitor or clinical research associate, appointed by the pharmaceutical company whose drug is being tested, is responsible for overseeing the trial.
But in India, doctors privately admit, the 8220;voluntary informed consent8221; obtained for clinical trials is rarely ever that. If the patients were informed that they were in a trial, most of them would not participate. But the very poor usually sign on the dotted line, assuming that the drug is for their benefit, that it is not experimental.

The guidelines:
All hospitals should have ethics committees and they should be responsible for not only giving their approval for the clinical trial
Adverse drug reactions during the course of a clinical trial will have to be submitted to the DCGI within 14 days if these are unexpected or serious effects, like death.
The ethics committee must ensure all information is provided to volunteers before taking their final consent to participate in the trials
Participants must be told of forseeable risks and discomforts adequately described and whether project involves more than minimal risk
Participants cannot be left in the lurch after the trials as most of the time, medicines/drugs that are being tested aren8217;t supplied after the trials are over
A trial has to be reviewed and documented within a reasonable time
Each ongoing trial has to be reviewed continuously
Every doctor is governed by the MCI Act. Any doctor or institution that indulges in wrongdoing can be prosecuted

THE INDIAN MARKET
1.5 billion dollars is the estimated market of clinical research in India by 2010.

WHY INDIA?
l India has several government-funded medical and pharmaceutical institutions with state-of-the-art facilities that are ideal centres for multi-centered clinical trials
India8217;s vast population makes it easier for drug companies and government agencies to find subjects critics call them guinea pigs for trials. While in the US, it might take nearly three years to get around 100 patients to conduct trials on them, in India the same number could be gathered in about six months
In terms of the cost efficiency, India works out cheaper. While clinical trials cost approximately 300 to 350 million abroad, they cost about Rs 100 crore in India.

When it can go wrong
Bangalore-based Biocon and Hyderabad-based Shantha Biotechnic were accused of conducting Phase III trials of genetically engineered drugs insulin for diabetes by Biocon and streptokinase for heart attacks by Shantha without prior approval of both the Drug Controller General of India DGCI and the Genetic Engineering Approval Committee. Reports said they applied for and got DCGI permission but applied to the GEAC only after the trials started. Some people died in the Shantha trial, conducted on seriously ill patients.
Mumbai-based Sun Pharmaceutical Industries Limited bypassed the DCGI and got private doctors to prescribe the anti-cancer drug Letrozole to more than 400 women for ovulation induction
In 1996, the US-based company Pfizer went to Nigeria during an epidemic of meningococcal meningitis to test a new antibiotic trovafloxacin on 200 affected Nigerian children, giving half of them the standard and best available treatment and the other half their experimental drug. 11 children in the 8216;trial8217; died.
And now, trials on 30 healthy volunteers at Pune8217;s National AIDS Research Institute continued for a whole year though it was known within the first fortnight that the vaccine had failed in tests in Germany and Belgium