Drug trials are very long and very complex. This is a brief overview of the stages of a standard clinical trial.
Clinical trials are the stage at which drugs are tested on humans. To get to this stage is a feat in itself, and a drug must go through rigorous testing in the lab and, if successful, animals before it is allowed anywhere near human test subjects. This blog post is focused on the testing in humans, but if you like I am more than willing to do a separate post detailing the preclinical stages, or the ethics surrounding drugs testing. If you feel like this is something you’d love to read, shoot me a message saying so on twitter.
Clinical trials tend to have four stages which have different goals. For most drugs, these are all the same. But for cancer drugs things operate differently, which opens up a whole new ethical and practical minefield (again, if you like I’ll happily do a post on cancer drug trials – just let me know if this is something you’d be interested in).
Phase I is the trial which most people can theoretically get involved with. These tend to be the ones you hear radio adverts for and the like promising a small reimbursement fee for your troubles if you participate in a clinical trial. It involves a sample of healthy volunteers trying the drug in increasing quantities. This may seem a little odd – why on Earth would a drug need to be tested on healthy people, surely that causes more harm than good? But actually it is for a very good reason – scientists need to test what effects the drug has when it should have none at all. By increasing doses from tiny to standard pill size they can assess how safe the drug is. If after the first tiny dose volunteers complain of headaches or other complications then it is unlikely that the drug will be able to painlessly help those with whatever it was meant to be targeting in the first place. This isn’t as scary as it sounds, as before this the drug has been tested in animals so scientists have an idea of when complications arose in another creature. However, it obviously isn’t the same as in humans, which are different creatures to lab mice etc. Essentially, the first phase of a drug trial is to find the maximum safe dosage of a drug which can be given to a person. If a drug passes phase I, it can go on to phase II.
Phase II is the stage at which the trial drug is used on patients with whatever the condition it is aiming to treat may be. However, this is where the main ethical debates can open up. At this stage of testing, the drug isn’t expected to work or be a cure. This stage of testing is about seeing if the drug can target what is required without side effects. Essentially, it is a repeat of phase I but with ill volunteers. This is the stage at which scientists re-evaluate dosages based on finding a balance between desired effects and side effects. If the drug only works at doses so high that patients also suffer from strong side effects, they realise that the drug is not going to work long-term in patients. If the dose deemed suitable from phase I doesn’t have any medicinal effect in patients at phase II level, then they must question how effective the drug is. The ethical questions can lie in how much patients actually understand that by being part of this stage of a trial they are unlikely to be cured and are just helping scientists to refine the test drug. Obviously the exact details of a phase II test are explained to potential volunteers beforehand so they can make an informed decision as to whether or not to participate, but some say that many patients could still have false hopes of miracle cures at this stage.
Phase III is the stage of a drug trial which most people tend to think of. It is certainly the stage which is mainly taught to children in schools where they don’t delve into the deep complexities of drug testing. This is the stage where there is a huge sample of patients with the disease and the actual effectiveness of the drug against a placebo or current medication is tested. These trials tend to be blind (the volunteers do not know if they have the test drug or not) or double blind (neither the patients nor the volunteers know who is taking the test medication). Phase III stage testing tends to be one of the longest and most expensive parts of a trial, because it is at this stage that the clinical effectiveness of the drug is being tested against a competitor. Many regulatory bodies (such as the European Medicines Agency) ask that at least two phase III trials are conducted and have similar outcomes before a drug can be licensed for clinical use. And even then, a drug may not be immediately licensed due to financial complications and patents etc (another scientific minefield which I’m happy to talk about sometime if you like).
Once phase III trials are completed, if a drug makes it onto the market, phase IV trials are essentially market surveillance of the drug in the whole wide global population. These tend to last two or more years so that any previously unfound effects can be addressed, such as the drug reacting badly with another type of medication some individuals might also be on etc. This is how drug safety is monitored amongst the general public, so that fatal drug tragedies that have happened in the past are minimised. If too many of these long term effects are found, then a drug may be withdrawn from the market for the safety of patients.
So that is a brief summary of how clinical trials work. As I’ve previously stated, this is not the model for all drugs, and some drugs for diseases such as cancer or HIV have different test processes. But this is a good overall outline to give you an idea of what someone means if they say they’re part of a drugs trial, or there is a piece in the news about someone being part of a drugs trial. The essential thing to remember is there’s a lot that happens before any potential cures or treatments are seen.