Before any drug is approved for human use by the FDA, and other regulatory agencies around the world, it must be proven to be both safe and effective.
A clinical trial (or study) involves research using human volunteers (also called participants or patients) that is intended to add to medical knowledge. In a clinical trial, participants receive specific interventions, most commonly drugs, according to the research plan or protocol created by the investigators. Clinical trials may compare a new medical approach to a standard one that is already available, to a placebo that contains no active ingredients, or to no intervention. Some clinical trials compare interventions that are already available to each other. When a new product or approach is being studied, it is not usually known whether it will be helpful, harmful, or no different than available alternatives (including no intervention). The investigators determine the safety and efficacy of the intervention by measuring certain outcomes in the participants.
Every clinical trial follows an action plan or protocol. It describes in detail how the research will be conducted, including, who can participate, the length of the study, details about tests and medications, and what information will be collected.
All patients will go through an “informed consent” process, where researchers provide potential and enrolled participants with information about a clinical study. This information helps people decide whether they want to enroll or continue to participate in the study. The informed consent process is intended to protect participants and should provide enough information for a person to understand the risks of, potential benefits of, and alternatives to the study.
A clinical trial that is well planned and well conducted offers participants the chance to:
The clinical trial protocol, developed by the researchers and other highly trained medical professionals, provides a list of characteristics to determine who can and cannot participate in a clinical trial. Examples of these characteristics, sometimes called eligibility criteria or inclusion/exclusion criteria, include items like age, what other medications someone might be taking, having high (or low) levels on various laboratory tests, and a number of other considerations that enable the researchers to make sure that they are testing the new drugs in the most appropriate patient populations.
The screening process is an important step to determine who can be selected to be part of a clinical trial. During this process, there are typically a number of tests and interviews to find out if the person is truly eligible for the clinical trial. The doctor or researcher in charge of the study (the principal investigator) usually does the screening, although some tests may be performed by other members of the staff, or even at separate locations.
The reason there are so many requirements is to ensure that the testing is performed as uniformly as possible. Selection can be very specific, based on the trial design. Unfortunately, that means that not everyone who applies for a clinical trial will be selected. People may not be selected if they do not meet all the eligibility criteria or if researchers already have enough people to complete the study. This does not mean that their contribution and willingness to participate is unimportant, quite the contrary, being open to the possibility of participation is critical for successful completion of these investigations and bringing new medicines to patients.
By contributing to the evaluation of volanesorsen (formerly ISIS-APOCIIIRx), participants may be involved in an effort that changes the
treatment landscape for generations to come.
In Phase 1 trials the new drug is usually tested in a small group of healthy volunteers. The main goal is to evaluate how safe the new drug is in humans. Researchers gather data in order to learn about how the human body metabolizes the drug, to identify common side effects and to determine a tolerated dose range.
In Phase 2 trials the drug is tested in a small group of patients with the condition being studied. The goal is to further evaluate the safety and efficacy of the drug, and to determine the best dose and regimen for Phase 3 trials.
After a Phase 2 trial has shown that a new drug is effective and safe in small numbers of patients, Phase 3 trials test the drug in a larger group of patients. Hundreds or even thousands of participants may be recruited from several different places. When the disease studied is rare, like Familial Chylomicronemia Syndrome (FCS ), the drug development process may involve a single Phase 2/Phase 3 study due to the rarity of the disease and limited patient availability.
The goal of Phase 3 trials is to confirm the preliminary evidence that the drug is safe and effective. The large number of participants enable researchers to assess how common and how serious any side effects are, to gather more extensive information on the extent to which the drug benefits patients and to determine dose and regimen schedules.
The data gathered from Phase 3 trials can then be used to apply for marketing approval from the licensing authorities. If the application is successful, this data is then used as the basis for the official drug information.
After the licensing authorities have approved the marketing of a new drug, post-marketing trials called Phase 4 trials are carried out. The goal is continued safety and efficacy monitoring when the drug is used more widely, in order to identify long-term risks and benefits and to identify any rare side effects.
The guidelines determining who can take part in clinical trials are called eligibility criteria. These criteria are designed to ensure that the type of patients most likely to benefit from the new drug take part and to reduce the chance that participants are put at risk. Sometimes researchers conduct early trials in a group of patients who are relatively similar, so that the outcomes can be reliably compared. If the results are encouraging, later trials may include a more varied patient population.
Volanesorsen (formerly ISIS-APOCIIIRx) Inclusion & Exclusion Criteria
Inclusion criteria state who may participate in a clinical trial. They may include a list of characteristics such as age, gender, diagnosis or disease stage.
Exclusion criteria state who may not participate in a clinical trial. For example, people who have taken a particular drug prior to the trial may be excluded. Pregnant women are often excluded from clinical trials because there is usually insufficient information available on possible risks the new drug may pose to the unborn baby.
The researchers who design clinical trials take great care to maximize the chances of benefits and to reduce the risks to participants. New drugs are always tested in the laboratory and in animals before they are tested in humans. Nevertheless, they may cause unexpected, unpleasant side effects. Before the trial starts, the researchers inform participants about any side effects that they know about, such as those that patients in earlier phase trials have experienced. All participants are monitored very carefully throughout the trial and sometimes also after the trial is completed. This enables the researchers to quickly identify any side effects and to take action to minimize them.
There may be some inconvenience to participants, including the need to attend the trial center regularly, to fill in questionnaires, keep a symptom diary or undergo extensive interviews and physical examination. Travel costs can usually be claimed back.
Benefits of participation in clinical trials include gaining access to potentially beneficial new drugs before they are widely available. In addition, patients may benefit from the extra medical attention as any changes in health status are picked up and acted on early. They may also feel empowered by the knowledge that they are taking an active role in their own health care and helping other patients by participating in the development of new treatments.
Each clinical trial is conducted according to a detailed study plan called a protocol. This is carefully designed by the researchers to ensure that participants’ health is safeguarded and that the trial will yield answers to specific research questions. The protocol includes the eligibility criteria, the proposed dosing and testing schedule and the trial duration.
Participants in RCTs are randomly assigned to two or more groups at the start of the trial. One group is given the trial drug and the other group is given an inactive treatment (placebo), an alternative treatment or no treatment. The group receiving the trial drug is called the experimental group and the other group is called the control group. Researchers follow both groups to compare the outcomes.
A placebo is a pill, powder or liquid with no treatment value (a “sugar pill”). It is given to patients in the control group of a controlled clinical trial. The placebo should have the same appearance as the active drug received by the experimental group, and should be administered in the same manner and with the same schedule.
In double blind trials neither the participants nor the researchers know who is receiving the trial drug and who is receiving a placebo. An independent third party codes the trial drug and the placebo materials and holds the code secretly until the study is completed or a significant adverse effect requires ‘unblinding’ where participants and researchers are informed as to which they received.
Participants and researchers all know what drug and what dose is being received.
Multi-center trials include patients and researchers in a number of different locations, often from different countries all around the world.
Before trials start, researchers are legally required to explain all the important information about the study to the participant. They must ensure that the participant understands the risks and benefits, that enrollment is voluntary and that if the trial is placebo controlled, they may not receive the active treatment. Once the participant agrees to participate in the study they would then sign an informed consent form.
Find out more about the volanesorsen (formerly ISIS-APOCIII Rx) trial or have your questions answered by contacting a trial location.Contact Us