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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.

  1. What are PaCTD ratings?
  2. PaCTD Rating Helpful Definitions
  3. PaCTD Ratings for Individual Trials

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 includes the following elements:
    • Consideration of disease heterogeneity
    • Use of scientifically justified eligibility criteria
    • Investigation of one or multiple biomarkers
    • 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.

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 [email protected]

Helpful Definitions

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 below to view a PaCTD Rating for: 

I AM ALS Patient-Centric Trial Design (PaCTD)

Brainstorm 

NurOwn

Open Label Extension No 0
Minimize placebo usage - 33% or less No (50%) 0
A side by side Expanded Access Program No 0
Part 1 Total 0
Part 1 Rating-Seats at the Table 0
Consideration of disease heterogeneity: e.g., Cross-Over Design or Delayed Start Design Yes 1
Use of scientifically supportable inclusion criteria, pre-defined subset analysis, re-randomization at trial conclusion to equalize outlier progressors between trial arms, or alternative controls (historical, algorithmic etc.) 24 months from onset, no older than 60 years of age. Some were scientifically justified. 0.5
Investigation of biomarker Yes 1
Independent Unblinded Review Panel that can communicate with FDA where substantial proof of “efficacy” emerges before end of trial No 0
Part 2 Total 2.5
Part 2 Rating-Advancing Science Quickly 0.1875
Use of Run-In Observation Period - 3 months not acceptable -1 month ideally Yes (3 months) 0
Use of novel methods: wearables, telemedicine visits, financial burden Telemedicine visits through COVID-19. 0.5
Part 3 Total 0.5
Part 3 Rating-Patient-Friendly 0
Total Rating 0.1875
x5 1.0625
I AM ALS PaCTD 5-Star Rating: 1-Star

Brainstorm’s clinical trial design was created before the FDA updated its ALS clinical trial guidance in the Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry in September 2019.


I AM ALS Patient-Centric Trial Design (PaCTD)

Orphazyme 

Ariclomol

Open Label Extension Yes-18 months 1
Minimize placebo usage - 33% or less Yes (33%) 1
A side by side Expanded Access Program No 0
Part 1 Total 2
Part 1 Rating-Seats at the Table 0.4
Consideration of disease heterogeneity: e.g., Cross-Over Design or Delayed Start Design Yes 1
Use of scientifically supportable inclusion criteria, pre-defined subset analysis, re-randomization at trial conclusion to equalize outlier progressors between trial arms, or alternative controls (historical, algorithmic etc.) 1
Investigation of biomarker Yes 1
Independent Unblinded Review Panel that can communicate with FDA where substantial proof of “efficacy” emerges before end of trial No 0
Part 2 Total 3
Part 2 Rating-Advancing Science Quickly 0.225
Use of Run-In Observation Period - 3 months not acceptable -1 month ideally No 1
Use of novel methods: wearables, telemedicine visits, financial burden telemedicine visits, travel reimbursement, drug shipped to home, home nursing visits 1
Part 3 Total 2
Part 3 Rating-Patient-Friendly 0.1
Total Rating 0.725
x5 3.625
I AM ALS PaCTD 5-Star Rating: 4-Star

Orphazyme’s clinical trial design was created before the FDA updated its ALS clinical trial guidance in the Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry in September 2019.


I AM ALS Patient-Centric Trial Design (PaCTD)

Alexion 

Ultomiris

Open Label Extension Yes - 2 years 1
Minimize placebo usage - 33% or less Yes (33%) 1
A side by side Expanded Access Program No 0
Part 1 Total 2
Part 1 Rating-Seats at the Table 0.4
Consideration of disease heterogeneity: e.g., Cross-Over Design or Delayed Start Design Subset Analysis & NFL 1
Use of scientifically supportable inclusion criteria, pre-defined subset analysis, re-randomization at trial conclusion to equalize outlier progressors between trial arms, or alternative controls (historical, algorithmic etc.) No age restriction, symptom onset 36 months, Riluzole and Radicava fine 1
Investigation of biomarker Yes 1
Independent Unblinded Review Panel that can communicate with FDA where substantial proof of “efficacy” emerges before end of trial No 0
Part 2 Total 3
Part 2 Rating-Advancing Science Quickly 0.225
Use of Run-In Observation Period - 3 months not acceptable -1 month ideally No 1
Use of novel methods: wearables, telemedicine visits, financial burden telemedicine visits, travel reimbursement 1
Part 3 Total 2
Part 3 Rating-Patient-Friendly 0.1
Total Rating 0.725
x5 3.625
I AM ALS PaCTD 5-Star Rating: 4-Star

 


I AM ALS Patient-Centric Trial Design (PaCTD)

Biogen

BIIB067 (SOD1)

Open Label Extension Yes 1
Minimize placebo usage - 33% or less Yes (33%) 1
A side by side Expanded Access Program No 0
Part 1 Total 2
Part 1 Rating-Seats at the Table 0.4
Consideration of disease heterogeneity: e.g., Cross-Over design or Delayed Start Design SOD1 1
Use of scientifically supportable inclusion criteria, pre-defined subset analysis, re-randomization at trial conclusion to equalize outlier progressors between trial arms, or alternative controls (historical, algorithmic etc.) 1
Investigation of biomarker Yes 1
Independent Unblinded Review Panel that can communicate with FDA where substantial proof of “efficacy” emerges before end of trial No 0
Part 2 Total 3
Part 2 Rating-Advancing Science Quickly 0.225
Use of Run-In Observation Period - 3 months not acceptable -1 month ideally No 1
Use of novel methods: wearables, telemedicine visits, financial burden telemedicine visits, state travel reimbursement 1
Part 3 Total 2
Part 3 Rating-Patient-Friendly 0.1
Total Rating 0.725
x5 3.625
I AM ALS PaCTD 5-Star Rating: 4-Star

Biogen’s clinical trial design was created before the FDA updated its ALS clinical trial guidance in the Amyotrophic Lateral Sclerosis: Developing Drugs for Treatment Guidance for Industry in September 2019.


I AM ALS Patient-Centric Trial Design (PaCTD)

The HEALEY ALS Platform Trial tests multiple treatments in one trial. This listing will be updated if additional drugs are added to the trial. 

Platform Trial 

Clene Nanomedicine

CNM-Au8

Biohaven Pharmaceutical Holding Co

Verdiperstat

Ra Pharmaceuticals

Zilucoplan

Open Label Extension Yes - up to 1 year + 1
Minimize placebo usage - 33% or less Yes (25%) 1
A side by side Expanded Access Program CNM-Au8 - Yes

Verdiperstat - Yes

Zilucoplan - Pending

1
Part 1 Total 3 3
Part 1 Rating-Seats at the Table 0.6 0.6
Consideration of disease heterogeneity: e.g., Cross-Over Design or Delayed Start Design Yes 1
Use of scientifically supportable inclusion criteria, pre-defined subset analysis, re-randomization at trial conclusion to equalize outlier progressors between trial arms, or alternative controls (historical, algorithmic etc.) Yes (36 months from symptoms). 

No upper age limit.

1
Investigation of biomarker Yes 1
Independent Unblinded Review Panel that can communicate with FDA where substantial proof of “efficacy” emerges before end of trial  No 0
Part 2 Total 3 3
Part 2 Rating-Advancing Science Quickly 0.225 0.225
Use of Run-In Observation Period - 3 months not acceptable -1 month ideally No 1
Use of novel methods: wearables, telemedicine visits, financial reimbursement Yes 1
Part 3 Total 2
Part 3 Rating-Patient-Friendly 0.1
Total Rating 0.925
x 5 4.625
I AM ALS PaCTD 5-Star Rating: 5-Star

Ra Pharmaceuticals’ Zilucoplan Expanded Access Program is pending.

Ra Pharmaceuticals’ Zilucoplan receives a 4-Star rating until the Expanded Access Program begins. A 5-Star rating is an average of the three drugs in the trial.

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