The following had been sent for posting on the Proventus website last week but, owing to email rather than phone communication, I was unaware that our web designer was out of the country for 2w and therefore out of the loop. As the lack of fresh content on the site has caused disquiet in some quarters, I have opted not only to try an find another work-around but also to put this posting directly onto the forum. It may not be the full outcome of the MHRA's discussions with Daval as that is still to be pronounced upon by the MHRA but it is at least of relevance. The posting is to be linked from the news page and reads as follows: -
Abstract from the Optic Neuritis trial paper
(with additional comments in italics).
The evaluation of a novel ‘goat serum’ therapy (Aimspro) in multiple sclerosis
Background: Anecdotal reports suggest dramatic immediate clinical improvement when HIV / B3 cell supernatant inoculated goat serum (Aimspro) is given to patients with Multiple Sclerosis (MS).
Objectives: This is the first randomized, double-blind, placebo-controlled study of this treatment and was designed to explore the effect of short-term administration of Aimspro in MS patients with fixed optic nerve dysfunction.
Methods: Twelve subjects (mean age 40.4 years, range 27-50, median EDSS 4, 7 females and 5 males) with clinically definite MS (6 RR, 5 SP and 1 PP) and a history of optic neuritis more than three months prior to the study, with residual visual impairment were recruited. Objective neurophysiological, functional magnetic resonance imaging and visual field assessments were performed and results compared between the two groups (Aimspro versus placebo). The study was powered to detect a 0.5% change in the fMRI primary outcome, with an estimated standard deviation of 0.4%, allowing for 10% subject dropout.
Results: Both Aimspro and placebo were well tolerated and there were no serious adverse events. Treatment with Aimspro showed no significant benefit in the primary or secondary outcomes: visual evoked potential amplitude or latency, or the amplitude of the BOLD response in the fMRI experiments. There was a significant treatment effect in the tertiary outcome of visual field function (p=0.02).
Conclusions: This study was exploratory and only measured immediate change after three treatment doses. The major visual deficit in most patients was peripheral and the only outcome that assessed this area significantly improved with treatment. These results are encouraging and support the need for further clinical trials.
J. A. Palace, G. Burke, A. Cavey, P.M. Matthews
University Dept. of Clinical Neurology
Oxford. OX2 6HE, UK
(Funding for the study was provided by Daval International Ltd., who own the patent on Amispro. However, the study was designed independently by the investigators, who were responsible for the conduct, analysis and interpretation of the results.)
Essentially there were 3 outcome measures in the trial but these were not necessarily in order of importance, just convention. Certainly the primary and secondary ones (VEP & fBOLD measurements) showed no change in response to treatment and the tertiary one (visual fields, which was "the major visual deficit" in the test subjects) was clearly improved but without being "dramatic" or "outstanding". These were objective and scientifically measurable features - what wasn't measured or reported on were the subjective results as perceived by the test subjects themselves.
It says in the discussion of the results towards the end of the full paper,
"For these reasons, only a dramatic improvement in visual function would be expected to show a significant treatment effect in these parameters."
- VEP & BOLD (ie. you can still have definite subjective improvement without a correspondingly good objective measurement) and,
"Furthermore, since fewer fibres originate from the periphery, reducing damage to just a few fibres may result in a detectable improvement in peripheral visual function."
- (ie. beneficial effects in a lower number of fibres - and therefore harder to measure - can still give an important change for the better to the patient).
In other words there are very good reasons why the correlation between the first two outcome measures and the subjective benefits in sight to the test subjects is not direct and linear. In plain english this means that any improvement that a patient may notice is not automatically reflected in what the scientists can measure. Vice-versa, a "no improvement" outcome measurement can still be experienced as a very worthwhile improvement to the patient. The choice of outcome measures doesn't seem to have been especially intuitive in hindsight but then again these have to be chosen in the design stage of the trial and not once the effects have been seen.
Other comments on these results posted elsewhere on the web seem to focus on the key statement of "no improvement in the primary and secondary outcome measures" rather than on what was experienced by the subjects, who apparently all reported a subjective improvement in vision on Aimspro. It would seem, at least in some regards, better to have a treatment that enabled a patient to "see" an improvement (irrespective of what the scientists' measurements said) than one which showed results in the laboratory but left the patient unaware of any change in their sight.
Proventus accepts the vital role of clinical research in assessing Aimspro but it should not be forgotten that patients are the ultimate beneficiaries of any success and not scientific instruments. Nor should an understanding of any research results be based on phrases taken from articles quite out of context - it must be made in the round and with a reasonably full comprehension.
- Finally, a comment from one of Proventus' members on the informed consent list...
"Furthermore, this trial was carried out over a very short time span (3w) and, from our own personal experience, I feel there was insufficient time to evaluate the true potential of the treatment, i.e. although my wife had an almost instant recovery with respect to the squint in her left eye, it was only after eight weeks of treatment that the visual blurring had cleared and it was several months more before she could tolerate bright sunlight."