Unlike a clinical trial, treatment is ongoing and open ended, accordingly, data can vary slightly over prolonged time.
Database at end of 2019
Data is harvested in real time as every patient’s monthly monitoring report is submitted on-line.The progression of the condition and its status is calculated by the ALS Functional Rating Scale-Revised (ALSFRS-R) which has 12 headings each with a score from 48 to 0, i.e. a maximum of 48 points. A normal person would score 48, whereas total paralysis would be 0.
RCH4 database
Datum points 14,608
Years of continuous-patient-treatment with RCH4
82.4 years
ALSFRS-R points
Average slowing of the disease decline rate when non-responders (14%) are excluded = 72.56%
Average slowing of the disease decline rate in whole treated population = 63.28%
Median slowing of the disease decline rate in the whole treated population = 53.83%
Average ALSFRS-R score when starting RCH4 is 34 points
Median ALSFRS-R score when starting RCH4 is 37 points
ALSFRS-R score range when starting RCH4 is 12 to 45 points out of a maximum of 48
Average historic functional decline over 14.17 months BEFORE starting RCH4 = -1.28 points per month
Average monthly decline over 16.44 months AFTER START of RCH4 treatment = -0.47 points per month
Since 2007, there have been more than 80 trials in ALS. None have demonstrated such, if any, measurable efficacy, short or long term, and further, all trials had carefully selected patients.*
Average starting score in PRO-ACT clinical trials database [>10,000 ALS subjects] is 40 points, i.e., disease less advanced when starting in those trials. Some 90% of patients are not accepted in ALS trials due to onerous exclusion criteria.Being a humanitarian charity there are no exclusion criteria for RCH4, first come first served, treatment is ongoing as previously stated.Comparison: Edaravone 6-month trial subjects start at 44 points & with onerous exclusion criteria
* Technical comment: the RCH4 analysis would equate to ITT as there is no exclusion or selection criteria, first come first served. Everyone asking for help is accepted only subject to paperwork. e.g., formal written diagnosis, case file, informed consent, doctors permission etc., and funds being available to treat the person for some years.
Decline rate excluding non-responders 14% (Responders 86%)
At three years of continuous RCH4 treatment, their median decline rate is slowed by 76.12%
At four years of continuous RCH4 treatment, their median decline rate is slowed by 93.50%
Average treatment length
16.64 months
Median treatment length
13.00 months
Length of treatment range
4 to 58 months
Highest number of RCH4 doses in one subject
564
Average number of doses per subject
131
Median number of doses per subject
104
Treated age range
Youngest 31 years, Oldest 83 years
Average age at start of treatment
53 years. 53% male
Median age at start of treatment
55 years
Disease onset
Limb 74%, Bulbar 15%, Unclear 11%
Sporadic or Familial
Sporadic 91%, Familial: 9%
Miscellaneous
12% of the subjects have PhD’s, 4% are medical doctors with independent neurologist’s diagnosis
RCH4 subjects concomitant ALS drugs
Riluzole 33% Edaravone 5% Both Riluzole and Edaravone 4%
RCH4 subjects taking no other ALS drug
i.e., do not take Riluzole or Edaravone 67%
Here, the definition of an ALS drug does not include medications to alleviate the consequential effects of the condition, e,g, salivation, pain relief, Botox, Nuedexta, etc., as previously stated*
Ethnicities
4 - Caucasian, African, Arab, Asian
Safety
No RCH4 related SAE reported
Monthly monitoring report compliance
100%
We insist on reports being submitted on the designated day, or if unavoidable exception, at least within 7 days from the designated reporting day
Confounding issues
The customary confounding issues, e.g., inclusion criteria, study design, placebo effect, cohorts, randomising, etc., are not applicable due to no exclusion criteria – first come first served basis - and far longer treatment than most clinical trials, i.e., continual open ended treatment for as long as charitable funding is available.Factors which affect the progression of the disease and the ALSFRS-R score are known, noted and factored for, e.g., Tracheostomy, NIV, Gastrostomy, Botox, Nuedexta, etc. The latter two do not address the progress of the disease itself - life extension - only alleviate consequential side effects.
Data mining
All ALS trials have failed to slow the progression long term. The sponsors of clinical trials inevitably search through their trial data to try find something - anything - that shows a trend towards efficacy, i.e., numerous end points. This can be misleading. Examples: Grip strength, lifting, fasciculation or FVC are highlighted if there is any positive indication or trend. Trends in these measurements are of no significance in the overall outlook. What truly matters is slowing the overall decline rate of the Functional Rating Scale (ALSFRS-R for which there is no substitute) and thereby increased life expectancy.
For RCH4 there is no data mining and no obfuscation. We offer only one end point: The ALSFRS-R - i.e, the slowing of the disease progression compared to the rate of progression prior to commencement of RCH4 treatment.
Bias
Due to monthly reporting, bias would rapidly exceed the envelope of credibility. As treatment is open ended, long term and ongoing, that fact further excludes it, as bias in decline rate reporting cannot continue.
A peer reviewed paper confirms that self-evaluation of the ALSFRS-R score concurs almost precisely with the same evaluations done in clinic. https://www.tandfonline.com/doi/full/10.3109/17482968.2011.633268
Controls
There is a potential confounding aspect to historic controls, which is the determination of the time of onset. Before starting on RCH4, a discussion takes place with the subject to review his or her history and from that information, and information contained in the subjects diagnosis file and the neurologists clinical notes, the time of onset is estimated. Where the information is unreliable, unavailable, or confused, decline rate since diagnosis is used as a baseline. Time since diagnosis averages 1.25 years before starting RCH4. The historic decline prior to RCH4 treatment start is almost exactly the same as the the decline rate in the placebo arms of untreated ALS subjects in the ALS clinical trials PRO-ACT database (again, >10,000 subjects). Historic control data is reliable due to being an average of more than one year of decline tracked for each subject before commencing that same subject’s treatment.
Placebos
Placebo effects do not normally last more than days or weeks - not years. In any event, PALS taking RCH4 never get a placebo (a dummy drug).