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Clinical Trials in OI: Participation, Results, and What They Mean
Clinical trials are an essential part of developing new treatments (like medications and vaccines) and testing whether a specific treatment under consideration is effective and safe.
Trials start with a small number of volunteer test subjects, and can grow to include thousands, or tens of thousands, of participants. Many clinical trials are controlled, randomized, and double-blind
- Controlled: a clinical study with a group who receive the new treatment being studied is compared to a matching set of people who instead receive another treatment like a placebo, a harmless “fake” treatment (a placebo-controlled trial), a comparator drug (often a drug that is already approved for the condition under study), or different dosages of the study drug
- Randomized: participants are randomly assigned either to receive the new treatment or to be in the control group
- Double-blind: both the medical practitioners and the clinical study participants do not know who is receiving the new treatment and who is receiving a placebo (either the sponsor of the study knows the “key” to who is receiving the study drug or a designated person not directly involved in the study has the key)
Overall, these design features help reduce bias in a clinical study and increase confidence that the results are reliable. In the United States, the National Institutes of Health (NIH) and the Food and Drug Administration (FDA) oversee clinical trials to help ensure they are conducted safely and appropriately. Although clinical trials for OI and other rare diseases may differ in size or specific details, they follow the same basic structure. At every phase, volunteers are enrolled and researchers follow a pre-established study plan, called a protocol, that outlines exactly how the trial will be conducted.
The phases of a study include:
- Preclinical or Non-clinical testing: scientists give the treatment to animals (like mice) to see if it produces a response and is safe
- Phase 1: a small group of human participants is examined, looking for safety, proper dosage amounts, and confirmation that it has some response in humans. Phase 1 may be done in healthy volunteers or in patients with the disease, or at risk for the disease, under study.
- Phase 2: hundreds of people; further tests safety and whether it stimulates a response in different types of people
- Phase 3: thousands or tens of thousands of people; determines if a vaccine or treatment is effective; a vaccine needs to be at least 50%-70% effective in protecting people. These are large enough to find relatively rare side effects that might be missed in earlier studies
- Phase 4: sometimes used after a treatment has been approved, this phase follows thousands of individuals and is used to find any long-term effects of the treatment
Individuals with OI play an especially important role in the outcome of clinical trials because they have a rare condition. Compared to more common conditions, rare disease-based clinical trials usually have far fewer participants than in the example listed above, making every volunteer even more valuable to the research process.
Questions about OI and Clinical Trials
The OI Foundation is committed to sharing clinical trial information with our community in clear, accessible language. We recognize that trial results can be complex. Our goal is to help individuals and families understand what the results mean, what they do not mean, and what next steps may follow.
How do clinical trials focused on treating people with OI differ from trials focused on a more general population?
Since OI is a rare disease, it is difficult to find hundreds, let alone thousands, of participants. Therefore, rare disease clinical trials involve fewer participants at each phase. More information on clinical trials and how they differ for rare diseases can be found in Dr. Adam Hartman’s “An Introduction to Clinical Trials” presentation from July 23, 2020.
Are clinical trials safe to participate in?
While potential risks differ from trial to trial and from person to person, participating in clinical trials is generally safe overall. Due to regulations in the US, volunteers are monitored at every stage of their involvement. Each participant in a clinical trial is informed about known and potential risks of the treatment being studied and will need to make an informed decision about whether those risks outweigh the benefits to themselves and the community when deciding whether to join the study.
Understanding Clinical Trial Results
How are clinical trial results evaluated?
When researchers design a clinical trial, they identify specific goals they want to measure. These are called endpoints.
- A primary endpoint is the main goal of the study. This is the most important outcome researchers are testing.
- A secondary endpoint includes additional outcomes that provide more information about how the treatment works.
For example, a study in OI might look at:
- Reduction in fracture rate (primary endpoint)
- Improvement in bone mineral density (secondary endpoint)
- Other measures of bone health or quality of life
Sometimes a study may show improvement in some areas but not meet its main goal.
What Does “Statistical Significance” Mean?
You may hear the term “statistical significance” when clinical trial results are announced.
This term does not mean that something is “important” or “unimportant.” Instead, it refers to whether researchers are confident that the results were caused by the treatment and not by chance.
If a study does not meet statistical significance for its primary endpoint, it means the data did not show strong enough evidence to confirm the treatment met its main goal under the study’s predefined rules.
This does not mean:
- The treatment had no effect.
- The research failed.
- The results are not valuable.
It means researchers must look more closely at the data to understand what happened.
Why Some Results Can Be Complex in Rare Diseases
Clinical trials in rare diseases like OI often include fewer participants than trials in more common conditions. Because of this:
- Every participant plays a critical role.
- Small differences can have a larger impact on results.
- It may be more challenging to reach statistical thresholds.
Researchers may continue analyzing data after initial results are released to better understand patterns, subgroups, or additional outcomes.
What Happens After Results Are Released?
When clinical trial results are announced:
- Researchers may conduct additional analyses.
- Findings may be shared with regulatory agencies like the FDA.
- Participants in open-label extension studies may continue treatment while data are reviewed. An Open-Label Extension (OLE) is a period after the main trial ends where all participants are given the active treatment. During this phase, both the researchers and the patients know which drug is being administered (the “blindfold” is removed).
- Patient advocacy organizations, like the OI Foundation, work to share clear and accurate information with the community.
Clinical research is a process. Each study contributes valuable knowledge that helps inform future research and treatment development.