Patient-Centric Trial Design (PaCTD) Rating Criteria
The PaCTD rating system was created by a group of patient and caregiver volunteers on the I AM ALS Clinical Trials Team. Their goal is to outline criteria for humane and efficient trial design. This rating system objectively evaluates trials based on select trial design elements in three key categories: optimizing access to investigational therapies, advancing scientific progress and if the trial is patient-friendly.
What are PaCTD ratings?
The PaCTD rating system is a 5-star rating system. The I AM ALS Clinical Trials Team used nine elements to assess clinical trial design. For definitions of the nine elements, see the definition section below. These elements fell into three primary categories and were given percentage weighting for the overall rating as listed below:
- Optimizing access to investigational therapies (60%). This category addresses whether a trial includes the following elements:
- Open-Label Extension
- Minimizes placebo usage
- An Expanded Access Program
- Advancing scientific progress (30%). This category addresses whether a trial incorporates design elements that may increase the chance of producing definitive trial results and advance the science of clinical trials in ALS. The following list provides examples but is not exhaustive.
- Consideration of disease heterogeneity such as using a predictive algorithm for trial inclusion or a crossover design
- Investigation of potentially regulatory grade biomarkers such as neurofilament light or digital biomarkers such as accelerometers
- Independent unblinded review panel for interim efficacy check-ins if warranted
- Being patient friendly (10%). This category addresses whether a trial includes the following elements:
- Use of run-in observation period
- Reduce travel burden by use of novel methods
PaCTD ratings do not measure or evaluate the treatment’s safety or efficacy. A high rating on this scale does not indicate promising science and a low rating on this scale does not mean the treatment is ineffective — it purely measures the design of the trial from the patient and caregiver perspective across the criteria outlined.
Note: As we learn more about ALS and potentially beneficial clinical trial design elements, the PaCTD rating criteria will be reevaluated for any necessary changes.
Within the ALS Signal dashboard you can hover your mouse over an individual PaCTD rating to see the specific elements included in a particular trial. If you have any questions about this rating system, please contact firstname.lastname@example.org.
The document referenced throughout this page as “FDA” is the FDA ALS Clinical Trial Guidance Document. It can be found here.
Open-Label Extension: The trial allows for trial participants to continue to access the treatment after the participation commitment in the trial has ended through Open-Label Extension (FDA p.5).
Minimize placebo usage: The clinical trial design seeks to minimize placebo administration to 1/3 of trial participants or less (FDA p.4 B1).
An Expanded Access Program: The drug sponsor provides access for patients who do not meet trial inclusion/exclusion requirements through an Expanded Access Program (FDA p.4).
Consideration of disease heterogeneity: The trial utilizes novel design features to sort out the effects of disease heterogeneity (e.g. crossover design; delayed start design; re-randomization of outlier disease progressors as part of a post-trial subset analysis) (referred throughout the FDA guidance). For more on ALS disease heterogeneity, click here.
Use of scientifically justified eligibility criteria: All trial inclusion/exclusion requirements are scientifically justified and do not reflect a cut and paste attempt to copy prior unsuccessful trials (FDA p.3).
Investigation of biomarker: The trial attempts to identify and substantiate novel disease-related biomarkers (FDA p. 3 and 7).
Independent Unblinded Review Panel: The trial utilizes an Independent Unblinded Review Panel. This panel has the ability to halt a trial due to patient safety concerns. It also has the ability to identify early indicators of success so that there can be an adjustment to the trial to speed consideration of review (FDA p.3).
Use of minimal run-in observation period: The trial utilizes a run-in period of one month or less. A run-in period is a period of time between when a patient is accepted into a clinical trial and undergoes initial tests/screening and when the investigational drug/treatment is administered to a patient (FDA p.6 #3).
Reduce travel burden by use of novel methods: The trial design utilizes telemedicine, wearable technologies, financial reimbursement and/or other novel methods to limit patient travel and the number of clinic visits throughout the trial (FDA p.7).
PaCTD Ratings for Individual Trials
- Click to view a PaCTD Rating for current trials:
- Click to view a PaCTD Rating for non-enrolling trials:
- Alexion (Ultomiris)
- Apellis (Pegcetacoplan)
- Biogen (BIIB067 (SOD1))
- Brainstorm (NurOwn)
- Orphazyme (Arimoclomol)
- Healey Platform Trial (Regimen A, B and C)
- Clene Nanomedicine (CNM-Au8)
- Biohaven Pharmaceutical Holding Co (Verdiperstat)
- Ra Pharmaceuticals (Zilucoplan)
- Reldesemtiv (Cytokinetics Courage)