Guest Post: Prof George Ebers

Dear Prof Ebers
You have been given star billing by people proporting the CCSVI lobby as a person who is not tainited by the pharma industry and are happy to report that

"That clinical trials of the MS drugs are basically worthless"

One of the bloggers asked "Are his comments regarding flawed outcome measures for DMDs, proof against using DMDs? The CCSVI activists certainly think so"

I was wondering if you had any time to write a post for our MS blog site on the above for lay people. Maybe you could pass comment on whether the same holds true, post the active immunosuppressives like tysabri. 

Prof Ebers Wrote

"David Baker kindly sent me some comments attributed to me to which I have pleasure in replying.

The comments are slightly out of context coming from a debate where I was taking the polarised side of there being major doubts about the outcomes used in MS trials. This is not a matter of opinion really since they have been subjected to careful study by the Sylvia Lawry Centre in Munich using results from some 40 trials, and have also been carefully evaluated in our studies on the natural history of MS where approx. 1000 patients were followed untreated for nearly 30 years on average. This population evaded so-called disease-modifying drugs as accrual ended in 1984 and by the time they were being promoted they were either too disabled to be considered or had done too well to want them.

In the first instance relapses were unrelated to long term outcome and surely no study should now be published with this as the outcome nor should studies be done in which patients are subjected to risk where this is the primary outcome. It is clearly unethical by consensus criteria, which reasonably insist that the outcomes have to be meaningful for risk to be taken on, otherwise no result of value to patients can come out of such trials. This result is supported by there being little from long term followup of the original treatment trials to indicate that relapses are a meaningful indicator of treatment effect when long term disability is considered. After all Long Term disability is the overwhelming medical social and economic impact of MS.

When the Sylvia Lawry results became apparent the response of the International Federation of MS Societies was to withdraw their funding. As contrary to the goals of MS patients and families this might have been, the following points need be made:

1) It was the only databank capable of assessing the results of all clinical trials leading to drug approval at the time and the only one with the raw data – only the placebo arms

2) Contrary to consensus recommendations by journals, almost all the large studies had been carried out with the investigators never having been given the raw data

3) The pharmaco-economics data from Scharr leading to the UK risk-sharing scheme had shown the outcomes were flimsy at best.

So I stand by what I said in the debate but rather than saying the outcomes are worthless it seems more appropriate to say they have not been validated. Frankly this is damning enough and if patients have been promised benefit in the long term, this is overstating the evidence.

Turning to disability, it was clear from the Sylvia Lawry Centre analyses that the definitions used for disability in the trials could not be validated either.

The response of the companies in general was to ignore these findings and continue to execute studies using unvalidated outcomes primarily because they were outcomes they knew they could beat. The Lancet has published several studies using unvalidated outcomes having had its industry funded reviewers reject the papers clearly showing these outcomes have little meaning in the context of the real disability patients fear.

If anyone wants the primary documents showing the flimsiness of the trial outcomes then please have someone who is prepared to distribute them email me for copies of the key papers, almost all of which have attracted editorial commentary, something indicating the editors thought them important.

I think the lesson from CCSVI which cannot be ignored is that the price of losing confidence in the medical system can be great and damaging on both sides of this debate. Physicians who are mystified by all this should keep this obvious conclusion in mind.

Best wishes

Prof GC Ebers

University of Oxford"

Sylvia Lawry founded the US National MS society USA in 1946 and by 1967 the worldwide Multiple Sclerosis International Federation (MSIF) with headquarters in London. The Sylvia Lawry Centre is a repository for clinical trial placebo data, because at some stage it will not be ethical to do any placebo arm to trials, when you have active drugs.