Every year, many cancer drugs are approved for use in Canada. Most of us don’t quite know the specifics of this process beyond that it probably involves some petri dishes in some scientific laboratory, advanced microscopes, and some may have heard of something called “clinical trials”. In this blog, we hope to give readers a broad overview of how cancer drugs are developed, all the way from an idea to something that a patient can pick up at their pharmacy.
Developing any drug, not just cancer drugs, is a long, arduous and very costly process. In fact, the vast majority of drugs that are studied never make it to market approval. Among those that do get approved, it takes an average of twelve years from its initial discovery to its approval.
Before attempting to discover potential drugs, researchers will try to understand the inner workings of the particular disease at the molecular level. The more scientists understand a certain disease, the greater the odds of discovering a potential biological target in the human body to aim to treat. Following that, researchers will attempt to identify promising molecular compounds that can affect the target and possibly become a drug treatment for the disease. Up to this point, all the research only involves studies in cells or small animals. When researchers identify the most promising drug, they will undergo additional studies called pre-clinical development. At this point, preclinical studies focus on testing in cells and animals at different doses and for different durations to find out details about how the drug is processed in animals and how it affects them. The goal of pre-clinical testing is to assess whether the drug will be safe to study in humans and to find the ideal starting dose to study for testing in humans.
If pre-clinical studies indicate that the drug is safe for further research, then it is ready to be studied in humans, and clinical trials can start. The goal of clinical trials is to study the efficacy and safety of the drug in humans. These studies are conducted under the close supervision of doctors and researchers in controlled conditions. There are four sequential phases of clinical testing and each phase is focused on evaluating a different aspect of the drug. A phase I clinical trial is the first time that a drug is tested in humans and their main goal is to assess its safety and also to find out how the human body processes it (also called metabolism). These studies only involve a small number of healthy or patient volunteers (less than 100 participants usually) and help researchers find out the side effects and safe dosing range in humans. Following that, if researchers deem the drug to be safe, it can progress to phase II clinical trials. About 70% of drugs tested in phase I are retained for further phase II testing. At this point, studies involve a bit more patient volunteers (up to several hundreds) to assess the efficacy and gather more safety data. From the range of safe doses established in phase I, researchers try to find the optimal dose for the best therapeutic effect while having acceptable side effects. Only about a third of drugs studied in phase II still show promise and move along to larger-scale phase III clinical testing. These phase III trials typically enroll many patient volunteers (up to several thousand) at many different places in the world and can take several years to complete. These phase III trials are considered pivotal studies and attempt to show that the drug is effective and safe in a large group of patients.
All clinical trials in phase I, II, and III are regulated and monitored by Health Canada to ensure the safety and well-being of the all participants and that they are conducted properly. When the phase III trials are completed, the drug is ready to be reviewed for approval by regulatory health agencies. In Canada, that is the role of Health Canada. Part 2 of the blog will cover the approval process..
References
Takebe, T., Imai, R., & Ono, S. (2018). The Current Status of Drug Discovery and Development as Originated in United States Academia: The Influence of Industrial and Academic Collaboration on Drug Discovery and Development. Clinical and translational science, 11(6), 597–606. https://doi.org/10.1111/cts.12577
How Drugs are Reviewed in Canada, Health Canada, 2015. http://www.hc-sc.gc.ca/dhp-mps/prodpharma/activit/fs-fi/reviewfs_examenfd-eng.php. Retrieved: April 12, 2020.
It’s Your Health: Clinical Trials and Drug Safety, Health Canada, 2013. http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/clinical_trials-essais_cliniques-eng.php. Retrieved: April 12, 2020.
Biopharmaceutical Research and Drug Development: The Process Behind New Medicines. PhRMA, 2015. http://phrma-docs.phrma.org/sites/default/files/pdf/rd_brochure_022307.pdf. Retrieved : April 10, 2020.
Cancer Drug Development: How Therapies Move Through the Pipeline, Cancer Therapy Advisor, 2019. https://www.cancertherapyadvisor.com/home/tools/fact-sheets/how-cancer-drug-development-pipeline-treatment-patient-fact-sheet/. Retrieved: April 10, 2020.