April 2023
Dr. Andrew Darke
ALS Action Canada
The diagnosis of ALS involves evaluation of Upper and Lower Motor Neurone signs and symptoms (UMN, LMN). The first diagnostic criteria were established by the World Federation of Neurology in 1994 at a conference in El Escorial, Spain.
These El Escorial (EE) criteria were revised in 2000 (the Airlie House, rEE Criteria) and again in 2007 (the Awaji Criteria, also rEE).
They include evaluation of both UMN and LMN involvement–and in how many body regions – to establish a diagnosis of Definite, Probable or Possible ALS.
However, there is now a substantial academic consensus that the EE/rEE criteria may be a barrier to appropriate diagnosis of ALS because of their lack of adequate sensitivity for making the diagnosis across all forms of ALS, and the erroneous implication that the criteria indicate varying levels of clinical uncertainty about the diagnosis.
A number of publications are arguing for their replacement by the Gold Coast Criteria formulated in 2019, which have been shown to have greater sensitivity than the EE/rEE criteria with a similar level of specificity. However, the EE/rEE criteria remain fairly standard in clinical trial protocols. This may be because trial designers are reluctant to depart from an accepted “standard” for ALS trials. It also has the advantage of enrolling a faster-progressing study population to provide a measurable efficacy signal (ie. a difference from placebo) over a conventional study duration of, say, six months.
But this leads to two types of problems:
- “Slow Progressors” are often excluded from clinical trials.
- CADTH uses a simplistic approach to establish reimbursement criteria, based on
the criteria used in clinical trials.
Consider the example of Albrioza, for which CADTH criteria require patients to have a diagnosis of definite ALS (El Escorial) and have had symptoms for 18 months or less. Analysis undertaken by the Calgary ALS Clinic indicates these criteria will restrict reimbursement eligibility to fewer than 10% of patients with ALS (206 patients with clinically confirmed diagnosis of ALS – 93% of patients who met the El Escorial definition of definiteALS had time since symptom onset exceeding 18 months (Jewett et al, Muscle & Nerve. 2022;1–2 ).
As a further example, consider the reimbursement criteria for Radicava under ODB, which include the EE/rEE criteria, plus restrictions on time since disease onset, plus criteria based on the ALS Functional Rating Scale (ALSFRS-R), plus some others, as follows:
“Diagnosis of definite ALS or probable ALS; and ALS symptom onset occurred within the past two years or less; and has a score greater than or the same as two (2) points on each of the 12 items of the ALS Functional Rating Scale – Revised (ALSFRS-R); and forced vital capacity (FVC) is greater than or equal to 80% of predicted; and does not require permanent non-invasive or invasive ventilation; and is under the care of a specialist with experience in the diagnosis and management of ALS.”
Many people living with ALS will complete the ALSFRS-R during clinical trials or in routine visits to the ALS Clinic.
The following are examples from my own experience as a person living with ALS that demonstrate the inappropriateness of using single item ALSFRS-R scores as a criterion for access to drug therapies under the Ontario Drug Benefit Plan (as one provincial example).
Such scores are neither an adequate indicator of overall function, nor of an individual’s capacity for response to an effective treatment:
Item 9: CLIMBING STAIRS
4 – Normal; 3 – Slow; 2 – Mild unsteadiness or fatigue; 1 – Needs assistance; 0 – Cannot do
If you are living with ALS and can climb stairs reasonably well but need to hold the handrail to do so (and who doesn’t), that may be defined as “needing assistance,” which would give you a score of “1,” which will eliminate you from accessing Radicava under ODB criteria.
Item 5a: CUTTING FOOD AND HANDLING UTENSILS
4 – Normal; 3 – Somewhat slow and clumsy, but no help needed; 2 – Can cut most foods
(>50%), although slow and clumsy, some help needed; 1 – Food must be cut by someone, but can still feed slowly; 0 – Needs to be fed.
If you are living with ALS and can walk, talk and more or less look after yourself but have difficulty in cutting food, you will be given a score of “1” and that alone will exclude you from drug access under ODB.
Two more examples:
Item 9: Handwriting – What if you can walk and talk and can grip a pen but cannot write?
Item 2: Salivation – What if you have too much saliva and often drool in the day?
In both cases you will score less than a “2,” so ODB will not pay for your Radicava.
We often focus on the problem of exclusion of Slow Progressors from clinical trials, but the problems with these linked criteria go beyond that. Any person who does not meet the EE/rEE criteria for Definite or Probable ALS; or any person for whom it who took more than two years (or 18 months) to receive a diagnosis; or anyone who scored a “1” on any of the 12 ALSFRS-R items may be excluded from access to drugs under provincial drug benefit plans.
The arbitrariness of these criteria make no sense. They are excluding thousands of Canadians living with the terrible disease of ALS from accessing drug treatments to which they are likely to respond, thus hastening their painful deaths.
ALS Action Canada has made several submissions to the Canadian Agency for Drugs and Technology in Health (CADTH) in an attempt to get it to remove the link it has implemented between the criteria for reimbursement of drugs for ALS and the inclusion criteria used to enroll patients in the clinical trials for these drugs.
But patient access to the three drugs currently approved by Health Canada for the treatment of ALS remain restricted under the current CADTH criteria for these drugs.
We are therefore calling upon the federal government, through Health Canada’s National Strategy for Drugs for Rare Diseases, to establish a framework for the review of drugs for ALS that is independent of the current CADTH framework.
This new framework would be scientifically valid, clinically appropriate and centred on the expertise and decisions of neurologists and neuroscientists in ALS clinics to determine the appropriate drug treatment for ALS patients on an individual basis and the associated reimbursement of drug costs.