From Discovery to Market: A Drug's Journey
A drug’s journey from discovery to market is a long and arduous one. First, a new drug must be developed in the lab. Then, scientists conduct pre-clinical research to test its toxicity, either in vitro (in cell samples) or in vivo (in animal studies) or both. Human trials of new drugs are split into several stages or phases – typically from Phase 1 in which the drug is tested for safety in a small number of people, to Phases 3 and 4 in which the drug is tested for both safety and efficacy in a large number of people.
- Only 1-2 of 10,000 compounds tested actually become licensed treatments.
- From start to finish, a drug’s journey takes an average of 12 years and $1.3 billion.
- Only one of ten drugs makes it from Phase 1 clinical trials to market.
How are clinical trials managed and approved?
Clinical studies are generally sponsored and/or funded by pharmaceutical companies, government agencies (the NHS), academic medical centres (university-affiliated hospitals), or charities, such as Parkinson’s UK or Cancer Research UK.
Strict regulations govern trials. A study must receive the go-ahead from regulators and clear an ethics review before commencing. A principal investigator manages a study throughout, and an off-site committee oversees patient safety. In the UK, clinical trials are overseen by a government organisation: the Medicines and Healthcare products Regulatory Agency (MHRA). In the US, the Food and Drug Administration (FDA) regulates trials. To get the go-ahead, trials must be well-designed, ethical, and as safe as possible.
Why a trial’s “success” is not always black and white…
The definition of success versus failure is not always clear-cut. All trials have secondary endpoints: stated aims beyond their primary endpoint. These allow for an in-depth examination of the data and can influence the likelihood of further trials. Many standard drugs – eg antibiotics and levodopa, the mainstay medication for Parkinsons – were a failure in initial clinical trials.
What is a randomised, double-blind placebo controlled trial and why is it considered the “gold standard”?
Volunteers are randomly assigned to take the real treatment or a placebo. This helps doctors make sure patients’ improvement is due to the drug being tested, and not simply from the benefits of participating in a trial or receiving medical attention.
The first nine months of the GDNF study included a placebo group. However, researchers thought it would be unethical not to offer all volunteers (who underwent brain surgery to participate) a chance to take the drug. For this reason, they extended the study another nine months, which was “open label” — everyone knew they were getting the drug.
Who can volunteer for a trial?
Some studies seek volunteers with the illness, while others need healthy volunteers. While those with the illness are rarely financially compensated (access to a treatment being considered a good-enough prize) researchers often compensate healthy volunteers for their time. A study typically pays between several hundred and several thousand pounds.
Trials: UK and the World
The MHRA receives more than 1,000 applications for new trials each year.
At any one time there are around 2,500 active trials ongoing in the UK.
More than 650,000 volunteers in the UK took part in clinical trials in 2017.
In 2018, more than 290,000 trials took place worldwide — that’s up from roughly 2,000 studies in the year 2000.
Most drugs - roughly 60 percent - fail in the leap from Phase 1 to Phase 2.
Life-threatening Outcomes
Today, more Brits than ever are participating in clinical trials. Even with stringent regulations and new safety standards (introduced after a disastrous clinical trial in 2006) they face risks. A few first-in-man clinical trials in recent years have resulted in serious injuries and even death.
- 2016, France - A volunteer dies when side effects of the drug being tested caused headaches and irreversible brain damage.
- 2006, Northwick Park Hospital, U.K. - Six volunteers experience multi-organ failure within hours of taking an experimental drug meant to treat leukaemia. Weeks later, several of them are still in intensive care. They all survive, but one loses his fingers due to gangrene. The study later becomes the basis for the Βι¶ΉΤΌΕΔ documentary “The Drug Trial: Emergency at the Hospital.”
- 1996, Nigeria - As Africa's worst-ever meningitis epidemic rages, Pfizer administers experimental oral antibiotic, Trovan, to hundreds of children. Eleven of them die. In 2009, Pfizer settles with the Kano state government out of court.
Pioneering Clinical Trials
- 1884 - First “blinded” medical trial. The Académie Française tests “mesmerism”, a leading theory of the times. A “magnetist” with a metal rod is able to induce hysterical fits in a patient - but, attempting the same while behind a curtain, does not produce any effect. The study proves the power of suggestion.
- 1947-1951 - Randomisation is developed during the interwar years by British statistician Ronald Fisher and is used in tuberculosis drug trials.
After a clinical trial…
After a drug proves safe and effective, a company can file an application to take the drug to market. At this point, it is reviewed by regulatory bodies, such as the FDA (in the US), the Medicines & Healthcare products Regulatory Agency (UK) and the European Medicines Agency. Once a drug is sold commercially, regulatory bodies continue to monitor the drug for safety, reviewing reports of problems.
