Clinical trials inevitably require overcoming a series of challenges. Behind these breakthroughs, there’s always an untold tale of scientific prowess and human persistence, creativity and empathy.
In the first Trial Trailblazers podcast initially hosted on BioPharma Dive, Nicole Latimer, CEO of Medrio, is joined by Dr. Gurdyal Kalsi, Chief Medical Officer at Asklepion Pharmaceuticals. They discuss the unique aspects of pioneering treatments for rare pediatric diseases.
In this conversation, Nicole and Gurdyal covered a range of topics, including:
- Designing rare disease research
- Selecting endpoints
- Developing protocols
- Working with patient community and the advocacy groups
- Understanding the role of patient-reported outcomes
- Using patient advocates to optimize the consent process
- Consenting in emergency settings
- Working with teenage patients and their caregivers
- Advising other rare disease researchers
Note: Not all questions are included below and responses have been edited for conciseness. We’ve included time stamps so you can check out the recorded audio to hear more.
What are the main study design components you consider?
[01:57]
A lot of the trials, particularly in rare disease areas, suffer from many challenges. Certainly, the size of the population is a big one. The other one is how you design a trial in order to recruit the patients you want included.
We conduct a fair amount of early work in identifying epidemiologically relevant populations, then examining their genotypes and performing various evaluations that will inform the execution of a trial.
The other key challenge is selecting endpoints. A lot of the time, with rare diseases, there is no consensus amongst the various specialty areas.
How do you select endpoints in your trials?
[6:11]
We start with a comprehensive evaluation of literature. When we start formulating the options that we might have, then we start looking at the do-ability of that particular endpoint. If we’re looking at time to event as an example, we will be looking at how many events do we need? What’s the sample size? Do we have that population available for us?
And then, we try to test it out in a smaller study. We would examine how the endpoint actually unfolds practically. If an endpoint is not available in an area, we then start looking for a potential surrogate endpoint. We start looking at the pathology, physiology, and biology of that disease.
Once we have those endpoints, we test them out. We also have to be aware that sometimes things don’t work out the way you plan them. Therefore, in the next phase, you change your endpoint to what you think is more likely to deliver the efficacy endpoint, considering any safety concerns.
How much time do you spend refining endpoints during protocol development?
[9:06]
Nearly 50% of my time is about getting the endpoints right. Getting them right takes a lot of thought. Sometimes, if it’s an international study, you need to determine whether this endpoint will be well-received in another region. So, it’s important to do a road test once you do have these endpoints.
How early did you engage with advocacy or community groups before starting a trial?
[17:47]
It all requires at least three or four years before you know your targets in community-based organizations. It also takes time to make inroads with associations, CEOs, presidents, and other medical community-based individuals, like patient advocates. These are the people who will tell you how to prepare the patient voice inclusion in your protocol.
It’s about bringing them on board early on so that they’re collaborating and actually telling you what the patient wants. And these days, when you select endpoints, you’ve got to make sure that the patient’s personal views are taken into account in what you’re going to measure.
Are patients more engaged when a primary or secondary endpoint is a patient-reported outcome?
[19:05]
Absolutely. If you bring a patient group together and are just an observer, you enable them to discuss among themselves what matters. When I hold a congress of patient advocates, you learn more sometimes by not speaking. We have to be cognizant of the emotional side that also plays a part when it comes to designing trials.
How do patient advocates and groups participate in your pre-consent or consent process?
[22:28]
They let us know whether patients are likely to be disturbed by what they’re reading. Are they likely to find it relevant information? Is it tailor-made to the audience? Are you presenting risks in the correct fashion and the benefits in the right fashion in the consent process?
Patient advocates tell us what the touchpoints are in the whole pathway of bringing the patient on board. And consent development is a key part where patient advocates should play a role.
How do you ensure the consent process is thorough and accurate in an Emergency Room setting?
[25:12]
A lot of the work that we do is guiding our sites to initiate conversations as early as possible. For example, you may be looking to recruit a patient who is going to present to an emergency room.
Before then, these patients do come for their routine care, and in those satellite clinics, outpatient clinics, infusion clinics, you can see whether they have the genotype that you’re looking for. If so, you start the conversation with them at that time about the possibility of participating in research.
How do you work to educate both adolescents and parents?
[29:01]
It’s just a good idea to bring the parent to a point where they also see that their adolescent kid is actually considering everything in a mature way.
Parenting is a hard situation, as we all know, particularly with teenage kids, and so a parent needs to be brought on board. Otherwise, there could be a conflict later on. And that conflict can lead to disruption. So to avoid that, we try and make sure that we have heard the parents’ point of view, and they have heard the adolescent’s point of view.
What advice do you have for those running rare disease clinical trials?
[31:06]
Know the target population that you want to serve. Know your population and everything that’s been done for them to date.
Put a lot of time and thought in knowing what the patients want. Prepare the target product profile, and within that target product profile, look at what the elements are that are desirable from a scientific, regulatory, and patient point of view.
Begin with the end in mind. Create the label that you want to use for the in-market experience, and then work backwards and create your clinical development plan from there.
Where can our listeners find you?
[37:14]
I am very much visible on LinkedIn so they could easily connect via my LinkedIn profile.
I would end by saying that picking your partners is equally important as picking the right population and endpoints. Once you have the right partner, collaborator, CRO partner, and any other required vendor, stick with them throughout your program.
Want more resources on running clinical trials? Read our eBook, “How to Run a Nimble, Cost-Effective Trial.”