Clinical Trials and Human Participants

Libby Meadows

Senior Editor

Loyola University Chicago School of Law, JD 2021

This past spring the world locked down. Stores were closed, everyone was required to work from home, and masks became the latest fashion trend. This shift occurred because a virus, Covid-19, began making its way around the world. It has been about 4 months since our society locked down for the protection of its people and while it is slowly opening back up there are fears that without a vaccine or cure for Covid-19 it is going to keep spreading and we are going to have to remained locked down. Many pharmaceutical companies are working night and day to create a vaccine that can be widely distributed to help stop the spread of Covid-19. A drug that is for humans needs to be tested on humans to ensure it works before it can be approved and sold.

Food and Drug Administration and Office of Good Clinical Practices

The Food and Drug Administration (FDA) is the United States agency that ensures products like food, drugs, cosmetics, medical devices, animal and veterinary products and much more is safe for US citizen to use and consume. The FDA works with pharmaceutical companies from the US and around the world to ensure that drugs sold in the US meet their standards. Clinical trials must be completed and passed before the drug can be sold. Within the FDA is the Office of Good Clinical Practices (OGCP). The OGCP is the focal point for the FDA for issues relating to the FDA’s clinical trials. It focuses on creating good clinical practices and solving human subject protection issues that arise with clinical trials. The OGCP also serves as a liaison to other governmental agencies to educated them about good clinical practices and human subject protection policies. Ensuring that clinical trials use the best practices and that human subjects are protected during the trials are essential to making sure all clinical trials are ethical and safe for the human participants.

The Belmont Report

In February 1976 the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (Commission) came together and created the Belmont Report. The Belmont Report summarized the basic ethical principles required for clinical trials using human participants. The three basic ethical principles the Commission presented in the Belmont Report were: 1. Respect for persons, 2. Beneficence, and 3. Justice.

Respect for persons is broken down into two ethical convictions. First, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. Respect for persons is also divided into two moral requirements. First, the requirement to acknowledge autonomy, and second, the requirement to protect those with diminished autonomy. These translate into present clinical trials as informed consents. People who participate in clinical trials must be provided adequate information about the clinical trial and their participation must be voluntary.

Beneficence, as used in the Belmont Report, is used to convey two obligations of clinical trials: 1. Do not harm, and 2. Maximize possible benefits and minimize possible harms. Researchers should never injure a participant regardless of the benefits they may find for others. Justice is tricky to define. There are five common formulas for justice: 1. To each person an equal shire, 2. To each person according to individual need, 3. To each person according to individual effort, 4. To each person according to societal contribution, and 5. To each person according to merit. The Belmont Report does not stated than any of those formulas is better than any other, it just offers them as something to think about when conducting clinical trials. The Belmont Report discusses previous unethical trials like the Nazis testing on prisoners in concentration camps or the Tuskegee syphilis study. These studies show that while there might not be a strict definition of what justice in clinical trials is, there are many examples of unjust trials. The Belmont Report was created to help ensure clinical trials like those never happen again.

Timeline of clinical trials

The principles above from the Belmont Report need to be considered through the entire clinical trial process. The process begins long before clinical trials start. Let’s take for example, the timeline for a vaccine to become approved. It can take between 10-15 years for a vaccine to be developed. First, at the exploratory stage, researches must identify antigens that might product an immune response in the human body. An antigen might be able to be used in the vaccine to prevent or fight a disease. If it can prevent or fight the process moves to the preclinical stage. In the preclinical stage the potential vaccine is tested in cells and then in animals. These test are required to show if the vaccine can create an immune response. If it does then the vaccine moves on to the clinical research stage.

At the clinical research stage, the manufacturer of the vaccine will need to submit an application for an Investigational New Drug (IND) to the FDA. The IND asks the manufacture questions like information about the vaccine’s testing and manufacturing, and how the manufacturer intends to test the vaccine moving forward. If the IND is approved by the FDA the vaccine moves into the three phases of clinical testing on humans. In phase one the vaccine is tested on 20-100 health adults to see how the vaccine works. It can take several months to complete phase one and about 70% of drugs move to the next phase. In phase two, it is tested on a larger group of human, up to several hundred participants. This phase can take several months to two years and about 33% of drugs move on to the final phase. In phase three, the vaccine is tested on 300-3,000 participants to determine the safety of the vaccine in a large group of people. It can take one to four years to compete phase three and about 25% to 30% move on to the next phase.

If the vaccine passes phase three, the manufacturer will submit a Biologics License Application (BLA) to the FDA. The FDA evaluates the data from the clinical trial to determine if the vaccine is safe and effective in preventing or fighting the disease it was designed to. The FDA will also go a step further and inspect the facility where the vaccine is manufactured as an additional factor to decide whether to approve it.

While hearing that most vaccines take 10-15 years to complete seems like a nightmare at this moment, the world is trying to work together to make a vaccine for Covid-19 as fast as possible. Having an intense approval process for a new vaccine is a good thing as it ensures our safety. We do not want any vaccine, we want a vaccine we know is going to prevent this virus from spreading. With time comes great things, and a truly preventative vaccine is worth waiting for.