From molecule to medicine: How are new drugs developed?
Medical research requires many different steps and stakeholders. We are taking a closer look at these.
Edward Jenner was a doctor who lived in England near the end of the 18th century. At that time, a serious and often fatal disease called smallpox was common.1,2 Dr Jenner noticed that milkmaids, who were exposed to a related but milder disease called cowpox, rarely developed smallpox. He began an experiment to show that intentionally giving a patient cowpox could protect against smallpox. He took the bold step of injecting a young boy with pus from a cowpox blister. A little while later, when exposed to smallpox, the boy was found to be protected. Jenner had discovered vaccination – a hugely important step forward in medicine. As a result of vaccination, smallpox no longer exists anywhere in the world and many other dreaded diseases have become rare.3
Patients receiving new medicines can only do so thanks to people around the world who contributed to medical research.
Doctors and scientists developing today’s new medicines also start with an idea and explore that idea through research. Today, the safety and welfare of the people who take part in research is closely monitored by independent ethics committees and by government agencies called medicines regulators. Well-known examples of medicines regulators are the Food and Drug Administration (FDA) in the United States4 and the European Medicines Agency (EMA) in Europe.5 In the mid-20th century, the regulators introduced some important new laws: before new medicines could be approved for use by the public, the manufacturer had to collect evidence to prove that the medicine was safe and effective.4 Turning a scientific idea into a new medicine usually takes 15 to 20 years… so what actually happens during medicine development, and why does it take so long? 6
What happens in medical research?
Research is all about answering questions. These questions are asked in several stages to carefully build up information about a potential new medicine. Many scientists are employed in researching diseases and looking for new molecules that might help.7 If they find a new molecule, they ask some basic questions. What is the structure of the molecule? How might it interact with natural chemicals in the body? Is it similar to any medicines we already know or use? By answering these questions, the scientists get clues about how the new molecule might be useful in humans. This is called basic or discovery research.8
If the scientists think the molecule could be useful, they begin pre-clinical research.8 This helps to find out if the molecule is harmful to living cells, which is important to do before giving it to humans. In some cases, scientists can answer these questions using cells grown in a dish. But research involving living animals such as mice or rats is often needed as well. The animals are protected by strict rules to ensure their welfare, and other research methods are being explored to minimize the use of live animals in future.9
Throughout the development of a new molecule, manufacturers also consider whether new medicines are really needed for a particular disease, and whether they could be provided to patients on a large scale if approved.10 This is called translational research, because it looks at whether something that seems promising in the lab can be translated into actual medicine.11, 12
Medical studies in humans are called clinical research.13, 14 Clinical research usually happens in stages or phases, during which some very important questions are answered under close medical supervision:
- Phase 1 studies – to find out how the medicine behaves in the human body, how much should be given (the dose), and whether it is well tolerated (i.e. whether it causes other troublesome health problems). The first few people to receive the potential new medicine are usually (but not always) healthy adult volunteers.
- Phase 2 studies – to look at whether the medicine may be helpful for a particular medical condition. These studies vary in length and size, but they usually involve up to a few hundred people, and last for weeks or months.
- Phase 3 studies – to learn more about whether the medicine works and is safe to use in a particular medical condition, and to look at whether the medicine is better than currently available treatments. These studies tend to be large, involving several hundred or a few thousand people. They may last for a year or more.
The collected evidence from basic, translational, pre-clinical and clinical studies (called ‘study data’) is presented to medicines regulators (e.g. the FDA or EMA). If the regulators decide that the evidence proves the new medicine is useful, it will be approved for wider use. Even then, the research doesn’t stop. Manufacturers and medicines regulators continue to ask for information from people who are prescribed the medicine by their own doctors. Rare side effects, for example, may only be seen after the medicine is given to a large number of people.15 Phase 4 studies, also called post-marketing studies, are the final phase of research. They look at how the medicine works outside clinical studies, and whether it has any other possible uses in human medicine.15
What is the role of patients in research?
Millions of people take part in clinical research each year.16 These people are all volunteers and are helping to increase our understanding of diseases and medicines. As a patient or a member of the public, there are many ways to get involved in research. You could donate blood or genetic (DNA) samples to help researchers learn about diseases and possible treatments.17-19 You could also consider taking part in a clinical research study, either as a healthy volunteer, or as a person with a particular medical condition. Your doctor may already be involved in a suitable study, or may be able to refer you to one in your local area. Patient spokespeople are also increasingly involved in committees that design studies or review research.20
In 2015, 39 new drugs completed testing and were approved for use in Europe.21 As a result, new treatment options are available for people with cancer, diabetes, heart disease and many other conditions.22 The patients receiving these new medicines can only do so thanks to people around the world who contributed to medical research.
- Brought to life: Exploring the history of medicine - Edward Jenner (1749-1823). The Science Museum. Available from: http://www.sciencemuseum.org.uk/broughttolife/people/edwardjenner
- Smallpox fact sheet. Centers for Disease Control and Prevention, 2007. Available from: http://emergency.cdc.gov/agent/smallpox/overview/disease-facts.asp
- Emergencies preparedness, response: Smallpox. World Health Organisation. Available from: http://www.who.int/csr/disease/smallpox/en/
- About FDA: Summary of NDA Approvals & Receipts, 1938 to the present. U.S. Food and Drug Administration, 2013. Available from: http://www.fda.gov/AboutFDA/WhatWeDo/History/ProductRegulation/SummaryofNDAApprovalsReceipts1938tothepresent/default.htm
- About us. European Medicines Agency. Available from: http://www.ema.europa.eu/
- Frequently Asked Questions: Research. The Alzheimer’s Society. Available from: https://www.alzheimers.org.uk/site/scripts/faqs.php?categoryID=200422&faqID=92
- Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 2015;33(8):1582-614.
- Regulatory Roadmap for the development of human medicinal products (Europe focus). The RQA. Available from: http://www.therqa.com/regulatory-roadmap/
- About us. European Society for Translational Medicine. Available from: https://eutranslationalmedicine.org/about-us/
- Working to reduce the use of animals in scientific research. Department of Health, 2014. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/277942/bis-14-589-working-to-reduce-the-use-of_animals-in-research.pdf
- Avorn J. The $2.6 Billion Pill — Methodologic and Policy Considerations. N Engl J Med 2015; 372:1877-1879.
- What is translational research? Wellcome Trust. Available from: http://www.wellcome.ac.uk/funding/Innovations/wtd027704.htm
- Clinical trials and medical research - Phases of trials. National Health Service. Available from: http://www.nhs.uk/Conditions/Clinical-trials/Pages/Phasesoftrials.aspx
- Clinical Trial Phases. U.S. National Library of Medicine. https://www.nlm.nih.gov/services/ctphases.html
- Suvarna V. Phase IV of Drug Development. Perspect Clin Res. 2010; 1(2): 57–60.
- Big rise in volunteers for medical trials. BBC News, May 2013. Available from: http://www.bbc.co.uk/news/health-22594635
- Donations for Laboratory Research Use. National Institutes of Health Blood Bank. Available from: http://clinicalcenter.nih.gov/blooddonor/donationtypes/lab_research.html
- Donating for Research. Human Fertilisation and Embryology Association, July 2015. Available from: http://www.hfea.gov.uk/donating-for-research.html
- Donating your tissue for research FAQs. Human Tissue Authority. Available from: https://www.hta.gov.uk/faqs/donating-your-tissue-research-faqs
- Public involvement in clinical trials: Supplement to the briefing notes for researchers. National Institute for Health Research, 2015. Available from: http://www.nihr.ac.uk/get-involved/INVOLVEpublicinvolvementinclinicaltrialsBriefingnotes2012.pdf
- Mullard A. EMA recommended 39 new drug approvals last year. Nature Reviews Drug Discovery 2016;15:77.