Updated October 12, 2020
a. “Since our review, we found a paper suggesting that serum IGF-1 concentrations in PALS were related to their survival (Sci Rep 2020;10:736). Thus, we change our “Mechanisms” grade from “D” to “C.” We found another relevant preclinical study showing that this drug can help a mouse model of motor neuron disease (Mol Med 2012;18:1261-1268). There are now multiple well-designed studies showing benefit of this or similar drugs in pre-clinical motor neuron disease models. Thus, we change our preclinical grade from “B” to “A.” Unfortunately, we found no new human cases or trials suggesting benefit. Thus, our conclusion is unchanged as follows:
“There remains no convincing evidence that any form of IGF-1, including Iplex can significantly slow progression in human ALS. We do not recommend that PALS pursue off-label IGF-1 in any form at this time outside of a well- designed trial.”
Updated July 24, 2023
As of July 2023 we found no new information that would warrant any TOE grade changes
Updated April 18, 2022
Since October 2020 (the date of our last update), we found no new publications that warrant TOE grade changes or changes to our conclusions.
Key Information
Click on any letter grade below for more info:
Preclinical Trials Grade:
A
Published: Aug 2009
The ALSUntangled program is off to a good start, with a number of specific requests from PALS being investigated by a multi-national group of ALSclinician-scientists. PALS and other clinician-scientists who want to become involved in ALSUntangledcan find instructions online (16)
Grade A: Shown in a peer-reviewed publication to act on a relevant mechanism in humans
Grade B: Shown in a peer-reviewed publication to act on a relevant mechanism in pre-clinical model(s)
Grade C: Theoretically and plausibly acts on an ALS-relevant mechanism in humans
Grade D: Acts on a biological mechanism but it is not clear that this mechanism is relevant in ALS
Grade F: Implausible; would violate known principles or laws of biology
Grade U: No useful information was found for this category
Grade A: Two or more peer-reviewed publications reporting benefits in well-designed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade B: One peer-reviewed publication reporting benefits in a well-designed study.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade C: One or more peer-reviewed publication(s) reporting benefits in flawed studies.
Animal studies are assumed to be ‘well designed’ when they follow published guidelines. When they deviate from these they are considered ‘flawed’.
Grade D: One or more non-peer reviewed studies reporting benefits (published on a website or in an abstract)
Grade F: The only studies available show no benefit
Grade U: No useful information was found for this category
Grade A: One or more peer-reviewed publications reporting benefits with validated diagnosis and benefits
Grade B: More than one unpublished report of benefit with validated diagnosis and benefits
Grade C: One unpublished report of benefit with validated diagnosis and benefits
Grade D: Subjective report(s) of benefit without validated diagnoses and/or benefits
Grade F: The only reports available show no benefit
Grade U: No useful information was found for this category
Two or more peer-reviewed publications describing benefits in well-designed randomized, blinded placebo-controlled phase III trials
Grade C: One or more peer-reviewed publications reporting benefits in a well-designed randomized, blinded, placebo-controlled phase I or II trial
Grade D: One or more peer-reviewed publications reporting benefits in a flawed trial.
Flawed trials means those in which there are identifiable problems with patient selection, randomization, blinding, controls or follow-up. These have ‘high or unclear risk of bias’ according to published criteria. Well-designed trials are those that have ‘low risk of bias’.
Grade F: The only trials available show no benefit
Grade U: No useful information was found for this category
Grade A: No exposed patients appear to have experienced harms
Grade B: More than 0% but less than 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade B (oral): More than 0% but less than10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D (intravenous): More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade C: At least 10% of exposed patients experienced harms (no hospitalizations or deaths)
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade D: More than 0% but less than 5% of exposed patients experienced death or hospitalizations
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade F: At least 5% of exposed patients experienced death or hospitalization
Grade U: No useful information was found for this category
