At the 2017 Global Genes Advocacy Summit, one of the break-out sessions discusses the drug development process. But it goes beyond this to educate us, the patients, on how imperative our role is to achieve the best outcome.
For those of you who aren’t sure about the general clinical trial process, here is a quick overview:
- There are four phases in clinical trials.
- Phase I is considered the first human trial. Before this is the pre-clinical phase, often animal trials. This is focused mainly on safety, to understand what the body does with the drug. They aim to understand the pharmacodynamics and pharmacokinetics. About 70% of drugs move on to Phase II from here.
- Phase II focuses on both safety and now efficacy, and is bigger than Phase I. It aims to answer the question: is the drug doing what we want it to do? It may include placebos and different dosages of the therapeutic. Only 33% of drugs make it to Phase III from here.
- Phase III is considered pivotal. It can test hundreds to thousands of people and from here, about 70-90% of drugs move forward from here.
- Phase IV is post-marketing, where “real-world” data is collected to make sure that the therapeutic has the same effect in the real world as it does in the clinic.
The amount of time it takes a drug to go to market from the lab is about 6 to 8 years at a cost of $2.5 Billion. Statistically, if you start out with 10,000 compounds in the lab, only one will make it to market. Once the drug is approved by the FDA, it may still take 6 months to 2 years for it to become available to the patient. However, when it comes to rare, the process is often changed a bit, as it tries to address the plethora of different challenges that come with rare.
Some questions researchers have during rare disease research are: How do we reach patients in such a small population? How to we access patients in remote areas, study them and then ensure data integrity?
Performance measures are another hurdle due to unknown natural history, or lacking biomarkers and surrogate endpoints. Then there’s the challenge of keeping patients engaged to stay in the study, so scientists get all of the information possible.
So, to address some of these challenges, scientists made a few adjustments to the process outlined above.
- Sometimes phase I and II (and sometimes even III) are often front-loaded or combined. They do this because quite frankly, testing a therapeutic in a healthy person just isn’t as informative as testing it on a patient. Additionally, sometimes there is such a small number of patients, they have to combine the phases. The lines get blurred here because researchers want to test efficacy as soon as possible- or as soon as researchers are sure of the safety of the drug.
- Phase IV may be required for approval, so the regulatory agency (e.g. the FDA) can see how the drug effects patients, especially if there was a small number in clinical trials.
This adjusted process doesn’t make drug development faster or more accurate, however. But what it does do is reinforces the needs for patients to be involved as early as possible in the process so that together, we can overcome the hurdles to move more efficiently toward treatments. With the help of the rare patient voice in every process of the trial, we can work as a team to make drug development better.
For example, researchers want to know what it’s actually like living with the rare disease, from symptoms to daily burdens. They want to know what a meaningful outcome is to a patient. During the actual clinical process, researchers want patient input in the areas of:
- Self-assessments to determine eligibility for the trial
- Trial awareness and how to best communicate it to the public
- Educational materials
- Informed consent
- Research site recommendations
- Greater representation of the patient community when measuring efficacy and progress of the trial
Patients can help inform researchers through natural history studies, patient registries, focus groups, surveys and patient advocacy organizations.
Researchers recognize that they need to work harder to close the communication loop with patients so that patients know their voices are important.
How serious are they about this? For starters, the FDA wants to know how the therapeutic in question makes the patient feels, functions and survives so much that it is indicated in the 21st Century Cures Act. The patient voice is becoming increasingly important, to the point where it’s becoming mandated and somewhat standardized. In the next few years, the FDA will come up with tools to incorporate patient engagement and experience in most clinical trials. They will then develop metrics around how that happens.
Researchers have already adjusted the trial process for the rare community, but they now realize they need the patient voice and feedback in order to steer them in the direction of truly meaningful results. This is what we want. Our interests are totally aligned here. It’s up to us to meet them half-way and remain active and engaged in helping them achieve positive outcomes. Do this through your advocacy groups and sharing your stories!