The new regulations--Drugs and Cosmetics (First Amendment) Rules, 2013-- for clinical trials has some problematic clauses, according to the researchers. One clause states that for an injury/illness, occurring to a clinical trial subject, he or she shall be given free medical management as long as required. "This does not specify what type or cause of injury. Thus a trial participant may be involved in a traffic accident or assaulted by someone, but under the open-ended clause, the trial sponsor has to cover all costs. This is unreasonable," said Suneela Thatte, President of Indian Society for Clinical Research.
Scientific agencies in the US such as the National Institute of Health have stopped trials in India. "For the research community in India it will now be near impossible to carry out trials of important low cost drugs, which may have an adverse impact on healthcare in the country. A number of such companies have now excluded India for clinical trials."
A reputed hospital and research centre in Bangalore was shocked when it received a letter from its research partners in Canada, asking the institute to halt all clinical trials with immediate effect.
"An international trial to test two cheap medicines --aspirin and clonidine-- which can reduce the risk of heart attacks after surgery was on in India. This study was sponsored by McMaster University in Canada. But it was stopped after the new regulations," said Prem Pais, dean and head, clinical research/training at St. John's Medical College here.
"Another trial to test an anti-clotting drug - Rivraroxaban- was sponsored by Bayer. In earlier trials, India was included, but the company withdrew after the new regulations. The health ministry needs to have a relook at the amended rules after consultation with researchers involved in clinical trials," Dr Pais said.
Researchers argued that the clause is "unethical" as it's an inducement for people to participate in a trial, even if it is risky, merely to get what amounts to "free health insurance". "Another clause calls for financial compensation to be paid over and above costs of medical management in the case in the event of any illness, considered trial-related. But there is no clarity on what constitutes trial-related injury. Again any medication cannot work all the time. A person whose cancer was not stopped from progressing may claim compensation under this clause even though the treatment was effective during the trial,'' said the ISCR chief.
"We must also make a distinction between death of a patient during a clinical trial and death due to clinical trial. Patients who participate in clinical trials already have a disease which could be mild or serious. The death of a patient in a clinical trial could be due to various reasons, including a natural progression of the disease, new diseases, age-related disorders, or an unrelated complication. Patients who participate in a clinical trial receive greater degree of medical care than they would have under regular treatment because of the high level of investigations and patient management that a clinical study protocol requires,'' Thatte said.
According to the ministry of health, 89 deaths were attributed to clinical trials between 2005 and 2012 of which compensation was paid in 82 cases.
* Number of clinical Trials in India
(*Source: Central Drugs Standard Control Organisation)
WHAT ARE CLINICAL TRIALS
A prospective drug has to go through a long process before being available in the market. The molecule is first born in a biochemistry laboratory where biochemists synthesize a large number of molecules, tailored to fit into receptors in human cells- normal or abnormal or cells of disease causing germs to promote their function, decrease their function or destroy them.
Molecules that seem promising are then tested in animal models to see if they behave as expected and to study how a living body handles the molecule, its side effects at various doses and to estimate what doses would be likely to be useful in humans. The few molecules which pass this phase, enter the phase of clinical trials. Initial human trials are in a few normal volunteers to test human handling of the molecule at various doses and any side effects. After this phase, a series of trials are carried out in patients suffering from the disease to test whether the drug is safe and effective.
Phase 3 trials are required by the drug regulatory agencies before a new drug can be approved. The usual requirement is for a double blind placebo-controlled trial. 'Controlled' means that there will be at least two groups - one which receives the new treatment and the other a 'comparison control group'. Randomisation ensures that a trial subject enters the experimental or control arm randomly to ensure the arms are truly comparable. A 'double blind trial' is one in which neither the subject nor the doctor knows which treatment the participant is getting using drugs which are identical in appearance. Finally a placebo is a tablet/injection which looks like the trial medicine but is inactive and inert.