What Happens in Phase I, Phase II and Phase III of a Clinical Trial?

With much of the country carefully following drug and vaccine trials for COVID-19, the stages of drug and vaccine testing and approval have been drawn into the spotlight from their usual place behind the scenes of drug development. Understanding the different phases of a clinical trial can help with deciphering the mass amounts of publicity surrounding COVID-19 treatment and vaccine advancements.

Before a clinical trial can be conducted, researchers must first create a drug or vaccine and conduct preliminary research in the laboratory, including cellular and possibly animal models. This can take anywhere from a few months to years depending on the amount of research required. In order to begin a clinical trial, preclinical studies, drug development and manufacturing documentation and a plan for conducting the clinical trial must be submitted to the FDA for clearance. The goal is to weed out dangerous drugs or vaccines before even one person receives it. Once the FDA (or other regulatory agencies in foreign countries) clears a drug or device for human studies, Phase I clinical trials can begin.

During Phase 1, a drug or vaccine is administered to a small number of people, usually less than 100, in varying doses. The goal of this phase is to determine safety and establish if safety varies according to dosage and type of patient. If a significant safety concern is found with the drug across all doses, then it will not be cleared to move to the second phase (in fact, phase 1 can be stopped). However, if a certain dose or doses are deemed safe and with acceptable and manageable side effects, then the clinical trial can proceed to phase 2. Because of tests run prior to the commencement of a clinical trial, the majority of new drugs and vaccines are cleared to move to Phase 2.

In Phase 2, several hundred people are usually given the new drug. Again, these people are typically healthy adult participants (in the case of a vaccine) or people who have the disease or condition (for a drug). However, the goal of this phase is to determine the efficacy of the new drug for its intended purpose and to obtain additional information about safety and the adverse-effect profile. A vaccine is tested to see if it prevents infection, while a drug is tested to see if it offers adequate treatment for a disease or condition. Another purpose of the second phase is to see if any side effects are uncovered in a larger group of people or are revealed over time or extended treatment. Only about one third of drugs make it past Phase 2.

If a drug makes it to Phase 3, the group of participants is usually expanded to a few hundred or thousand patients depending on the anticipated indication. This group typically includes people of diverse backgrounds, especially in age and health status. Phase 3 is how researchers confirm the efficacy of a drug or vaccine in varying circumstances. Phase 3 also allows for monitoring of a drug or vaccine for adverse effects over several years in typical circumstances. All of these numbers of subjects and patients is, of course, dependent on the type of disease.  In new drugs for rare diseases (e.g., genetic diseases or cancers), where there may only be a few hundred or thousand patients in the world, the size of trials may be scaled back dramatically.  

In a health crisis (e.g., a pandemic) or where there are no available treatments for a life-threatening disease (e.g, cancer), the FDA may grant researchers the ability to accelerate development and apply for fast track status or receive an emergency authorization based on less data than usually required.

If all phases of a clinical trial are successfully completed, the drug can be marketed and distributed to all patients who are indicated for treatment, but the FDA continues to monitor the new drug or vaccine for reports of adverse effects. If there are a significant number of new or unexpected adverse effects, the FDA may require additional warnings, studies or even remove the drug from the market. While this process is extensive, it ensures that new drugs and vaccines are held to the highest possible scientific standard for safety and efficacy.

Are Robots the Future of Surgery?

Robotic surgery was created to assist surgeons with routine, minimally invasive procedures. Robot-assisted surgeries tend to take less time and result in decreased pain for the patient. However, some surgeries, including certain heart surgeries, have remained very invasive, open procedures. Now, more surgeons than ever are able to complete advanced and difficult surgeries with the assistance of robots.

While the first use of robot-assisted surgery occurred in the 1980s, and laparoscopic surgeries have been common for years, the use of robotic technology has ramped up in recent years due to technological advances. The advantages of robotic technology for surgery exist for both the patient and the surgeon. Advanced cameras help surgeons gain greater visibility, robotic arms remove tremors that could cause tissue damage and robotic technology allows for surgery with less cutting. For the patient, this means a shorter recovery and can even mean fewer complications.

The Da Vinci System is one of the most famous robotic surgery systems, offering options for cardiac, gynecological, colorectal, urological, thoracic and general procedures. Other popular robotic surgery systems include Mako by Stryker, NAVIO by Smith & Nephew and Monarch by Auris Health, but each of these systems are more limited in their potential uses than the Da Vinci.

However, while robot-assisted surgery may be the future of many surgical procedures, no robot can replace the role of the surgeon in any procedure. While robots can reduce recovery times and improve outcomes by assisting surgeons with visibility and performing less invasive procedures, the knowledge and craft of doctors is irreplaceable. The future of robotic surgery is promising, but doctors are the future of surgery.

Sources: Yale Medicine, Da Vinci, Britannica