4. New Drug Application Submission, FDA Approval, & Post-Marketing Surveillance
After successful completion of one or more Phase III trials, the drug’s sponsor submits a New Drug Application (NDA) to the FDA. The NDA contains comprehensive data detailing the drug’s safety, efficacy, tolerability, manufacturing process, and proposed labeling. The FDA carefully reviews the submitted data to determine whether the drug’s benefits outweigh its risks. This review process includes an assessment of the drug’s safety, efficacy, and quality. If the FDA approves the drug, it can then be marketed and made available to patients.
This whole process can be modified and shortened for orphan diseases and some cancers, for example starting Phase 1 trials in patients (often called Phase 1b studies) and potentially allowing for accelerated approval based on a Phase 2b study, with full approval granted after post-marketing studies are completed (if they support approval).
And just when you thought the process was over… Once a drug is released to the market, many companies then conduct post-marketing surveillance studies, which involve ongoing monitoring of the drug’s safety and effectiveness in the real world. Occasionally there are negative side effects that occur in only a small percentage of patients, and these are only discovered once the drug is being taken by a larger number of people than participated in the Phase III trial.
One very serious example of this happening was with the painkiller Vioxx. Despite passing the rigorous FDA approval process, research later published in the medical journal Lancet found that approximately 88,000 Americans had heart attacks resulting from taking Vioxx, and of those, approximately 38,000 people died. If you’d like to know more about what went wrong and how the post-market research ultimately led to Vioxx being pulled from the market (and the many, many lawsuits involved!), we recommend this succinct [OPTIONAL] NPR article that provides a chronology of unfortunate events.
In a more innocuous example, some drugs that were grandfathered into the system prior to more rigorous FDA testing standards remain on the market despite evidence that they are not effective. If you’re curious about this, we recommend this [OPTIONAL] short NPR article on the lack of effectiveness of phenylephrine, a purported decongestant and common ingredient in cold medicine that was FDA-approved before current standards.