I. What is wrong with the current ALS clinical trial landscape?
I am going to answer this question with a vignette: An individual with ALS decides to enroll in a clinical trial that they found on ClinicalTrials.gov. They check to see if they meet the trial requirements and are pleased to learn that the trial includes their type of ALS. Not only that, but the trial site is located close to their home and only requires one visit every two weeks.
This story is invented. It rarely happens that way.
Information about enrolling in ALS clinical trials is not readily available to recently diagnosed ALS patients. The trial information that is available, is not easily comprehensible for those not in the clinical research field. Even if a patient knew what a clinical trial was and started looking on clinicaltrials.gov, they would spend months sifting through phases, mechanisms of action, enrollment criteria and maybe, just maybe, they would find a trial that does not exclude them. How can you be excluded from a trial? Below is the exclusion criteria for a ALS dietary supplement trial that started in 2017:
- Forced vital capacity <40% of predicted
- Dependence on mechanical ventilation for more than 12 hours per day
- Exposure to any experimental agent within 30 days of entry or at any time during the trial
- Women who are breastfeeding, who are pregnant or are planning to become pregnant
- Women of childbearing potential not practicing a medically accepted form of contraception
- Enrollment in another research study within 30 days of or during this trial
- Mini-Mental State Exam (MMSE) score <20
- Patients with symptomatic cardiac disease or hypercholesterolemia
- Patients with myocardial infarction within 6 months of this trial
- Renal dysfunction defined as BUN and creatinine >2xULN
- Known mitochondrial disease
- BMI<18.5
- Prior use of a 4:1 ketogenic diet or Atkins diet within 1 month of this trial
- Impaired liver function, defined as AST or ALT of 3xULN
- Patients who have a pacemaker or other internal electronic medical device
- Known allergy or hypersensitivity to milk or soy products.
Yes, if you are allergic to soy you are disqualified from this trial…you get the point.
Exclusion criteria is only one of the many hoops ALS patients must jump through before they find the trial that is right for them. The length of ALS trials usually prevents the majority of patients from being able to complete them due to their rapid disease progression. Not only that, but what if you spent 6 months in a clinical trial in which you were a part of a placebo group? At that point, you spend 6 months not receiving an active drug, and you are probably disqualified from joining other trials. Okay, what if you are receiving the active drug? There probably weren’t any biomarkers that tracked your disease progression, so you would never know if your disease stopped progressing due to the drug or if you just had a slow progressing form of the disease. The list goes on…
II. What is I Am ALS?
I AM ALS is a patient-led ALS organization that was co-founded by Brian Wallach and his wife, Sandra Abrevaya, in 2019. Brian was diagnosed with ALS when he was 37 years old. He has an incredible story that has been told on several platforms. This video is a does a great job of visualizing it. I AM ALS empowers and enables people living with ALS. They are inserting the patient voice into politics and drug development and making sh*t happen. What exactly are they doing? I AM ALS has 3 key focuses: Advocacy, Patient Services (Navigation Program) and Research. This blog post focuses on their advocacy work.
III. What is I AM ALS doing to fix ALS clinical trials?
I AM ALS is visiting drug developing companies and introducing their Patient Centric Trial Design (PaCTD). What is PaCTD? It is a five star rating system that demands the following (this list is not exhaustive):
- Scientific justification for all exclusion criteria
- Minimization or elimination of placebo controls (e.g shared placebo group)
- Use of biomarkers
- Open label extension available for all trial participants
- Use of novel methods for data capture
- Unblinded Independent Intern Efficacy Review Board” (IRB) to review trial results while in progress to identify subsets of patients who are benefitting
- Significant consideration for access to Compassionate Use (e.g Expanded Access)
The companies’ trial designs are rated according to how well they address the requirements in the PACTD. It is important to note that this rating scale does not in any way comment on the efficacy of the ALS trial. It is simply a way for people living with ALS to select the trial that most humanely considers their trial participants.
The PACTD requirements have the potential to impose serious financial strain on drug developing companies. They also have implications in the IND-enabling studies which happen well before Phase I clinical trials. That is why the I AM ALS constituents are meeting with drug developers early in their development process.
This is a time of true clinical trial innovation. I AM ALS is making drug development companies uncomfortable, but in the best way. In a way that demands critical thinking and promotes improvement. Patient centricity is not the end to profitability.
