A
clinical trial must go through many layers of review before it can start enrollment. Every layer of the process is intended to protect patient safety.
U.S. Food and Drug Administration
Before a potential medication or therapy can be tested in people, it must be reviewed and approved for further study by the
U.S. Food and Drug Administration (FDA). The sponsor of the study -- usually the drug company -- must submit an application for an investigational new
drug. In this application, the FDA reviews the results from initial laboratory studies to determine that the potential drug poses very few risks to people and that any risks are worth the possible benefits.
Once the FDA approves the application for an investigational new drug, it must approve all clinical trial plans (protocols) and make sure all required guidelines are being followed.
When a drug or therapy has finished three phases of research, the FDA determines whether the new drug or therapy will be approved for use by other people with cystic fibrosis.
To approve the new drug, the FDA requires that the study results show that the new therapy will be as effective as or better than medications or therapies that are already available. The potential financial cost to patients is not a factor in approval.
As part of the patient safety process, there are many other people who review clinical trials to make sure the possible benefits outweigh the risks. They include:
- Study sponsor and medical monitors
- Therapeutics Development Network (TDN) compound review, Protocol Review Committee and Clinical Research Executive Committee
- Institutional review boards (IRBs)
- Data safety monitoring board (DSMB)
- Site principal investigator
Study Sponsor and Medical Monitors
The study sponsor, often the pharmaceutical company that developed the drug, develops a protocol, which includes a guide for how safety will be monitored. During the study, medical experts hired by the sponsor monitor adverse events in real time. Adverse
events are considered negative
side effects that one may experience, whether it's related to the drug or not. For example, an increased cough during a clinical trial would be considered an adverse event,
and it would be monitored throughout the study.
Therapeutics Development Network
After the FDA approves the clinical trial, the sponsor submits the trial to the
Therapeutics Development Network. The TDN is a collaborative
network of more than 80 care centers that conduct CF clinical trials. The CF Foundation is the primary source of funding for the TDN.
The
TDN Coordinating Center, based in Seattle, conducts several reviews before approving a trial for centers within the TDN. In some
cases, this starts with a compound review.
A
compound review is conducted when different
drug compounds in the same treatment category (such as anti-inflammatories) are being developed for clinical trials. The goal of this evaluation is to independently assess
whether the compound being considered is likely to be more effective than other compounds in the category. If it isn't, the compound will not move forward into clinical trials within the TDN.
All multicenter clinical trials that are conducted within the TDN are required to go through the network's two-step
protocol review process, consisting of reviews by:
- The Protocol Review Committee, which is made up of experienced adult and pediatric CF investigators, research coordinators, at least one biostatistician, and a patient representative. The committee conducts a thorough review of the protocol and generates
a detailed critique, as well as ratings for scientific merit, feasibility, and study design.
- The Clinical Research Executive Committee, which includes CF Foundation executives and senior CF researchers, assesses how the protocol fits within the overall priorities of the Foundation for clinical research and assigns a numerical rating for strategic
fit.
The protocol reviews help clinical trial sponsors and principal investigators:
- Enhance study design
- Ensure efficient conduct within the CF center network
- Protect patient safety
- Maintain the accuracy of study data and specimens
- See how their studies fit with the priorities of the CF Foundation
Institutional Review Board
After a clinical trial has been approved by the FDA and the TDN, the company developing the potential drug identifies the research institution(s) where it will test the drug.
The next level of approval must come from each research institution's institutional review board (IRB), an independent committee that reviews the entire study proposal to make sure that the benefits of the trial are greater than the risks and that volunteers
will be monitored closely for any complications and safety. The IRB also ensures that anyone enrolling in the clinical trial has been given information that is easy to understand and allows them to make an informed decision about participation.
IRBs will approve only research that deals with medically important questions in a scientific and responsible way. The IRB continues to monitor study conduct throughout the trial and is notified of any adverse events.
Data Safety Monitoring Board
All clinical studies must have a
data safety monitoring board (DSMB), an independent committee of experts in clinical care, clinical and
basic science research, bioethics, and biostatistics.
“My patients are my heroes … And when they volunteer to do this research, they need to be protected and that's what we do.”
- Wayne Morgan, M.D., chairman of the Data Safety Monitoring Board funded by the Foundation
Although both the TDN and DSMB are sponsored by the Foundation, the two entities are not only organizationally separate from each other, the are separate from each other and have separate review processes. The protocol reviews complement each other and
are done in parallel.
The primary responsibility of this board is to protect the safety and welfare of patients who participate in the TDN and other Foundation-sanctioned clinical trials and to ensure the accuracy and consistency of those trials.
Each CF clinical trial is assigned a data monitoring committee, which reviews the protocol before volunteers enroll to ensure it includes appropriate testing and monitoring to protect participants' safety.
An important feature of each data monitoring committee is that it monitors the clinical trial in real time and is able to see what is called “unblinded” data. In other words, when reviewing the data, the committee members can find out if a participant
is being treated with the study drug or with a placebo. This close monitoring allows the committee to pick up early signs of potential side effects. If necessary, the committee
will suggest changes or even stop the clinical trial to protect participants' safety.
Many of the risks for people with CF who participate in clinical trials are inherent to the disease, and thus are shared across different clinical trials. Maintaining a core of expertise specifically related to CF makes the DSMB very effective at monitoring
CF clinical trials and protecting CF research participants as new drugs are developed.
Site Principal Investigator
The study site principal investigator (PI) is a doctor who specializes in the care of people with CF and is responsible for the oversight of a study at a particular site. The most important part of the PI's responsibility is to monitor the safety of the
study participants at the PI's site.
Before enrollment, the PI reviews your or your child's health to see if you or your child can safely participate in the study. During the study, the PI reviews all safety measurements including pulmonary function testing and blood work, watching for any
changes in health. The PI also reviews any changes in symptoms.
The PI's first priority is always the participant's safety. If at any time the PI feels the study is not in your or your child's best interest, the PI has not only the right -- but also the duty -- to remove you or your child from the study.
“Your care team isn't going to intentionally put you at risk or weigh the odds when it comes to your health -- it always comes first. I think trusting that is important.” -- Jodi Marquez, an adult with CF, who has participated in two clinical trials
Study Participant's Role
In the
informed consent process, a participant is given all the available information about the study process as well as possible risks and benefits. It is important for you to
ask as many questions as needed so that you can feel comfortable about participating.
During the study, you keep your doctor informed about how you or your child are feeling and any concerns you may have, and you follow the study plan as explained to you during the informed consent process.
We call people with CF who participate in clinical trials, and all those who support them, trailblazers. Help us
blaze a trail to better treatments and a cure for CF.