Why many drugs fail their development pathway

Readers should be aware that many drugs fail to achieve the therapeutic hopes of the researchers developing them. This is normal, as drug development is an enterprise with a high risk of failure. A first step in the development process might be a computer simulation of how a potential drug might interact with a virus-infected cell. If the simulation suggests promise, then the next step might be lab experiments with cells, viruses and the drug in question.

Even if a simulation was promising, a drug might prove to have unwanted effects in lab experiments or there may be unexpected findings. For example, a computer simulation might first suggest that a drug could be an effective antiviral against SARS-CoV-2. However, lab tests could reveal that the concentrations of the drug required to suppress this virus are far higher than what can safely be achieved in people.

Even if a drug advances past initial test tube studies, it then has to be tested in animals. Again, unexpected effects could occur, such as unforeseen toxicity.

Having passed all these stages, the drug may then be a candidate for preliminary safety assessments in people (a phase I clinical trial). Here again, drugs can fail because laboratory and animal experiments may not replicate the identical symptoms or effects a germ can have on people.

Even if a drug passes phase I in people, it is possible that it will fail in subsequent phases because of other reasons. The organs and systems in the human body are interconnected and interact in ways that are not always captured by laboratory and animal experiments.

Many scientists are aware of these issues and have been trying to find ways of increasing the likelihood of success for candidate drugs that enter the development pathway. Several analyses have found that rates of success for candidate drugs are generally higher today than they were decades ago. Despite that good news, many candidate drugs will encounter challenges in their development process.  

—Sean R. Hosein


  1. Wong CH, Siah KW, Lo AW. Estimation of clinical trial success rates and related parameters. Biostatistics. 2019 Apr 1;20(2):273-286.
  2. Smietana K, Siatkowski M, Møller M. Trends in clinical success rates. Nature Reviews Drug Discovery. 2016 Jun;15(6):379-80.
  3. Seok J, Warren HS, Cuenca AG, et al. Genomic responses in mouse models poorly mimic human inflammatory diseases. Proceedings of the National Academy of Sciences USA. 2013 Feb 26;110(9):3507-12.
  4. Waring MJ, Arrowsmith J, Leach AR, et al. An analysis of the attrition of drug candidates from four major pharmaceutical companies. Nature Reviews Drug Discovery. 2015 Jul;14(7):475-86.
  5. Low LA, Mummery C, Berridge BR, et al. Organs-on-chips: into the next decade. Nature Reviews Drug Discovery. 2021 May;20(5):345-361. 
  6. Meyer MN, Gelinas L, Bierer BE, et al. An ethics framework for consolidating and prioritizing COVID-19 clinical trials. Clinical Trials. 2021 Apr;18(2):226-233. 
  7. Edwards A. What are the odds of finding a COVID-19 drug from a lab repurposing screen? Journal of Chemical Information and Modelling. 2020 Dec 28;60(12):5727-5729. 
  8. Tummino TA, Rezelj VV, Fischer B, et al. Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2. Science. 2021 Jul 30;373(6554):541-547.
  9. Aronskyy I, Masoudi-Sobhanzadeh Y, Cappuccio A, et al. Advances in the computational landscape for repurposed drugs against COVID-19. Drug Discovery Today. 2021 Jul 30:S1359-6446(21)00335-4.
  10. DiMasi JA, Feldman L, Seckler A, et al. Trends in risks associated with new drug development: success rates for investigational drugs. Clinical Pharmacology and Therapeutics. 2010 Mar;87(3):272-7.