NewsSpeak & OffLabel: maybe off-label prescribing will be come a global reality?

 When it comes to putting your money where your mouth is the US is right up there! #NewsSpeak #OffLabel

“The Patient-Centered Outcomes Research Institute (PCORI) will fund four comparative clinical effectiveness studies in MS (see below). Well done to all the successful PIs.”

“Let’s hope the rituximab data is good enough for NHS England  to adopt off-label prescribing in MS; at present they won’t. At last, we will know which of the two heavy-weight orals, fingolimod or DMF, is superior. It is good news for the field that someone is prepared to fund an independent head-2-head study. The importance of this trial cannot be underestimated; with fingolimod coming off-patent we need new data to over-turn the 2nd-line indication we have for prescribing fingolimod in Europe. A cheap small-molecule oral therapy, with high-efficacy, will almost certainly lower the entry level price for treating MS. However, I am a bit disappointed that teriflunomide was not included in this head-2-head study; when you look at the subgroup analyses I think teriflunomide is more efficacious long-term than the headline results of the phase 3 trials indicate. I predict teriflunomide would have a reasonable chance of holding its own in terms of efficacy against both DMF and Fingolimod. Another point is that teriflunomide is also coming off-patent soon; so another cheap entry level drug to mix it up.”

Four Studies to Assess Effectiveness of Multiple Sclerosis Treatments Receive $19.6 Million in Funding from PCORI: Studies will give patients evidence to help them choose among therapies. PCORI July 19, 2016

Press release

WASHINGTON, D.C. (July 19, 2016) – The Patient-Centered Outcomes Research Institute (PCORI) Board of Governors today approved nearly $20 million to fund four comparative clinical effectiveness research (CER) studies that will assess several therapies used to treat multiple sclerosis (MS) or its symptoms.

Two studies will compare the benefits and harms of various treatments collectively known as disease-modifying therapies (DMTs) that aim to reduce MS attacks or slow the disease’s progression. Another will evaluate the effectiveness of medications used to treat fatigue, a common, often debilitating problem for people with MS. The fourth will assess whether people with MS in rural and low-income areas can get similar benefits from rehabilitation therapies if they are provided via telehealth versus in a clinic.

The studies will be designed and conducted with significant input from patients, family caregivers, and other healthcare stakeholders. Each will include people with MS; nurses, physicians or other clinicians; or representatives of other stakeholder groups on their research teams. The four awards were among 35 totaling $153 millionapproved today by PCORI’s Board.

“PCORI is delighted to make these new awards addressing crucial evidence gaps and questions of vital interest to the more than 400,000 people in the U.S. living with multiple sclerosis,” said PCORI Executive Director Joe Selby, MD, MPH. “These studies will provide significant new evidence to help patients, their families and their clinicians decide more confidently which of the therapies available to them will work best given their needs and preferences.”

“These PCORI awards are a welcome and much-needed infusion of new MS research funding for important real-world questions about treatment strategies and their effectiveness,” commented Bruce Bebo, PhD, Executive Vice President, Research, at the National Multiple Sclerosis Society, a group representing patients that will be an engaged stakeholder partner in several of the studies. “The projects should provide important evidence for the best ways to address troubling symptoms like fatigue, and the potential for using technology to deliver needed rehabilitation approaches to people in remote areas,” he added.

The four projects approved today are:

Rituximab: An $8.5 million study comparing the effectiveness of rituximab, a biologic drug, to other commonly used disease-modifying therapies in individuals with the relapsing-remitting form of the disease. Rituximab is increasingly being used as an MS therapy in Sweden and the United States. The study will be based at Karolinska Institute in Sweden and conducted in collaboration with Kaiser Permanente Southern California. In particular, it will assess the comparative safety outcomes of the medications.

Excercise -based rehab: A $5.8 million study of whether patients get as much benefit from an exercise-based rehabilitation program delivered via Internet or telephone as when the therapy is provided in a clinic. Evidence shows that exercise, yoga, and other such therapies can alleviate symptoms and improving function, but clinics that can provide such services are scare in rural and low-income areas. The trial, led by a research team based at the University of Alabama at Birmingham, will be conducted in Alabama and Mississippi.

Fatigue: A $1.9 million study of three medications frequently used to relieve fatigue in people with MS. There is little evidence about how well these drugs – amantadine, modafinil, and methylphenidate — work compared to one another in providing relief for MS-related fatigue. The trial will be led by a team based at the University of California at San Francisco.

Fingolimod vs. DMF: A $3.3 million award for the first pragmatic trial comparing the benefits and harms of the oral DMTs fingolimod and dimethyl-fumarate. These drugs are commonly used to treat MS and are believed to be similarly effective, but both have side effects and they have not been compared directly to one another. The trial will be led by a research team based at the Foundation of the Carlo Besta Neurological Institute in Milano, Italy, and include sites in the United States, Europe, and Israel.

The new studies address evidence gaps and questions that people with MS and other healthcare stakeholders identified as their top priorities through PCORI’s process for topic selection. A multi-stakeholder workshop in April 2015 brought together patients and participants representing groups advancing research on the disease as well as clinicians, government agencies, industry, and health insurance plans to refine the questions that became the focus of PCORI’s funding announcements.

All of the awards are approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract.

8 thoughts on “NewsSpeak & OffLabel: maybe off-label prescribing will be come a global reality?”

  1. It is a disappointing selection of studies from my perspective. First, the delivery of care in the EU vs the US and how these are handled are very different and pose some issues. To award over 60% of this US tax money to Italian and Swedish researchers is difficult to understand. The total amount allocated for MS research was $50 MILLION and they only gave out $19.6 Million, claiming the other studies submitted weren't even close.I was part of the 2015 'stakeholder' group and fought to have a DMT study proposal included but it was not meant to look at just two drugs- that is the work of a drug company study. Our community wants to know how all the DMTs stand against each other. The real-world comparison of these drugs has been done initially and reported on at both AAN and CMSC this year . … make the point – "hope the rituximab data is good enough for NHS England to adopt off-label prescribing in MS" while ocrelizumab is up for approval in the US and this off-label use will most likely fall out of practice. We had also asked to see studies on complimentary /alternative therapies and that went no where. For a refresher on what was recommended, the listing of the proposals suggested by the stakeholders is at my blog. i hope you will take the time to read it because it has some excellent questions for researchers. PCORI CER Results – a long-time supporter of PCORI and of MS research, I find the announcements last week a disappointment and little to celebrate. As for the remaining $30 Million, we can only hope they will reissue the call for proposals. BTW – it was not only MS they shorted, they also didn't completely fund opioid abuse studies and several others. Many of us who were part of this process are perplexed by the end results.

  2. The purpose of the studies is to find answers. The money should go to whoever can do it best, wherever in the world they may be

    1. RE: "Why Rituximab and not Cladribine?"Cladribine is an unlicensed drug; this funding is for comparative effectiveness research of licensed innovations. You may be aware that Merck has not submitted oral cladribine to the FDA, so there is a chance it will never get licensed in the US for MS.

    2. I would think that rituximab is unlicensed for MS too, cladribine is licensed for hairy cell leukemia, however rituximab is more likey to be used in US I guess. However, you can only get funded if someone applies to do the work and so I guess someone applied to study rituximab and no-one has applied to do cladribine…it is the scary MS drug avoided by the establishmentGiven the likelihood of ocrelizumab getting approval, rituxan is an obvious cut price option as some may not afford the price Roche will charge, but an odd one given the potential arrival of ocrelizumab, but one would need to see the application as i am sure a case has been made to justify this Counting the number of people getting rituximab on some of the ECTRIMS poster there were well over a 1,000 people recieving rituximab in Sweden and given their registries one may have thought that you would have a fair idea on safety. However being chimeric there are going to be about 20% of people making anti rituxan antibodies compared to less than 1% with ocrelizumab.

    3. I spoke to ProfG apparently Cladribine was suggested…I guess there are too many people that have not read the Pakpoor et al. 2015 paper and are running scared.

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