Why do nine in ten drugs that reach human trials never get approved?
Of 5,000 to 10,000 candidate compounds, about ten reach people, and most of those still fail.
▶ Start the storyBecause the road from a promising molecule to a medicine is built to reject most travellers. A candidate for a new drug may be one of 5,000 to 10,000 compounds. About 250 of these show enough promise in laboratory tests, mice and other animals, and about ten qualify for tests in humans. Before a first human dose, the law requires an assessment of toxicity to the major organs, and the work must recommend the dose and schedule for that first use.
Human testing then climbs four steps. Phase I trials, usually in healthy volunteers, determine safety and dosing. Phase II trials give a first reading of efficacy in small numbers of patients with the disease. Phase III trials are large, pivotal tests of safety and efficacy, and most are randomized, double-blind and placebo-controlled. Phase IV continues after approval.
Step 1: Phase I
Healthy volunteers: safety and dosing
Step 2: Phase II
Small groups of patients: first look at efficacy
Step 3: Phase III
Large pivotal trials: safety and efficacy
Step 4: Phase IV
After approval: ongoing monitoring
Most candidates do not make it. They fail either because of unacceptable toxicity or because they do not prove efficacy in Phase II or III. A study of the 1980s and 1990s found that 21.5% of drugs that started Phase I trials were eventually approved. For 2006 to 2015 the figure was 9.6%.
Share of drugs starting Phase I that were approved
| Approved | |
|---|---|
| 1980s–1990s | 21.5% |
| 2006–2015 | 9.6% |
The complete process to approval may take 7 to 15 years. The high failure rate is called the attrition problem. A trial volunteer in phase I does not gain a direct health benefit and is generally paid a fee for time.
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Recap
Each phase asks a harder question, and most drugs fail one of them.
💡 A trick to remember it · Phase I: is it safe? II: does it hint at working? III: does it truly work? IV: what happens later?
Surprising fact · The success rate from Phase I to approval was 9.6% in 2006 to 2015.
Connects to
- 🎲 How does a trial keep hope from fooling everyone?
- 🎯 How did scientists turn one immune cell into a drug factory?
- 💊 What did thalidomide change about how drugs are tested?
- 📈 Why does making a new drug get more expensive even as the tools improve?
- 🗄️ Why can published science look more certain than it really is?
Sources (2)
No source, no claim. Every fact in this lesson (16 claims) cites at least one of these.