how new drug is discovered
In a decision that will go a long way in boosting the clinical trial industry in the country, the Union health ministry has removed the restriction on the number of clinical trials an investigator can undertake at a time. At present, no investigator should conduct more than three trials at any given period of time. Removing the restriction, the ministry has now empowered the ethics committee to take a final call on the number of clinical trials an investigator can do at any given time after examining the risk and complexity involved in the trials.
Earlier, there were objections from the stakeholders including the clinical trial organisations in the country against the health ministry’s decision to restrict the number of clinical trials an investigator can do at a time as they felt that the restriction was impeding clinical research in the country as this has led to the under-utilisation of the healthcare infrastructure developed over the last one decade on one hand coupled with high attrition rates in the industry.
Experts were of the opinion that studies conducted for vaccines may require 10,000 trial subjects whereas studies on cancer may require 60 to 70 trial subjects. Therefore, restricting the number of studies for an investigator is not justified in the interest of clinical research. Institutional ethics committee should be given the power to govern the number of studies an investigator can undertake based on requirement of a particular study because in each therapeutic area the study requirement varies immensely.
In the light of widespread resentment against the restriction, the Union health ministry convened several meetings with the industry associations and other stakeholders. To deliberate stakeholders concerns and the way forward relating to some issues on conduct of clinical trials in India, two such meetings were held on 20.8.2015 and 6.10.2015 under the chairmanship of secretary, ministry of health in which other experts in the field were also present.
After detailed discussions and deliberations, the ministry decided to do away with the restriction. “As regards restriction that no investigator shall conduct more than three trials at any given period of time, it has been decided to remove this restriction and it is further decided that ethics committee after examining the risk and complexity involved in the trial being conducted/proposed shall decide about how many trials an investigator can undertake”, Drugs Controller General of India (DCGI) Dr GN Singh, in his order said.
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Drug Development Process
The development steps
First, a scientist or a team comes up with an idea for a new drug to treat a disease or a vaccine to prevent one.
If it’s a drug, they will test the compound against the virus or bacteria in vitro – that is Latin for in glass. They might put the drug into a glass plate in which a virus is growing to see if the drug kills off the bugs.
The next step involves testing the experimental product in animals – in vivo, which is Latin for within the living. These animals ideally develop symptoms similar to what humans experience when they are infected with the bacteria or virus in question. If the drug or vaccine cures or protects susceptible animals, it might do the same for people.
Mice are commonly used as models in the early stages of animal testing, but something that works in mice would generally be tested in another animal species as well. Mice are very different from people and the evidence is more persuasive that a drug or vaccine will work if it is effective in a species more closely related to humans than mice. In influenza research, ferrets are often used. In Ebola research, macaques and other non-human primates are employed.
If the animal experiments are successful, the developers of a drug or vaccine will move to test it in people. That work begins with what is called a Phase I trial. These studies are small, often enrolling just a few dozen people, and they are carried out in healthy volunteers. These studies are designed to answer a couple of key questions: 1) is this experimental product safe for people to take, and is it safe to continue to test it? 2) what is the right dose to use in people? When it comes to the dose, researchers are trying to hit the sweet spot: enough so that the product will be effective, but not too much, to limit the risk of toxicity or harmful side-effects.
Phase I trials cannot tell you if a drug or vaccine is effective or not, because the people don’t have the disease that the drug will target, though they can provide hints. In the Phase I trials for Ebola vaccines, for instance, researchers measured the immune response the vaccines provoked.
If a Phase I trial is successful, researchers move on to a Phase II trial, which involves larger numbers of volunteers–say, between 100 and 300. If a drug is tested, the trial will enroll people who have the disease that it’s targeting; if it’s a vaccine, the volunteers are often people at risk of contracting that disease. For instance, researchers could test a malaria vaccine in an African country where malaria occurs. Generally the volunteers will be divided into two groups and will be randomly selected to get either the experimental product or something else to compare it with. That could be a placebo,* a “dummy” pill or shot that should have no effect. Or if there is a drug already available for a condition, an experimental new drug might be tested against it. This kind of study is called a Randomized Controlled Trial (RCT)*
It may seem odd, and even cruel, to give some patients a placebo–why not give everybody the actual drug? The reason is that by comparing the effects of a drug to that of a placebo, researchers can determine how much effect the drug really has. It is considered the fastest and most reliable way to get an answer about whether the drug or vaccine works. And until it is clear that the product being tested does work, it is generally not considered unethical to withhold it. Once a study reveals that a drug works, however, researchers can no longer ethically compare it to a placebo.
A Phase II trial will start to make it clear whether the drug or vaccine being tested actually works; because more people are involved than in Phase I, it will also tell researchers more about the side-effects. If it appears that the drug or vaccine is effective, the developers will proceed to a Phase III trial, which involves still larger numbers of people. This is the level of study that is meant to answer the question: Does this drug or vaccine really work?
Phase III trials typically enlist thousands of people. For the Ebola vaccine trial in Liberia that kicked off early 2015, for instance, 27,000 people were expected to take part.
If a Phase III trial shows that a drug or vaccine is effective, the company developing the product can apply to a regulatory agency such as the U.S. Food and Drug Administration or the European Medicines Agency for a license to produce the product for sale.