Since I am in a clinical trial, I promised to post on this thread, but I never seemed to find the time at a moment when I was sufficiently clear-headed to write anything coherent. I seem to more and more plagued by sleepy brain fog in the afternoons and evenings. I think I need a three-day weekend every weekend.
I thought it was interesting in the article that oncologists take such a financial hit for doing clinical trials instead of chemo, but I don’t have the impression that neuros get that kind of a kickback from the DMD companies. I’m sure they get their share of perks, but even if they do trials, they’re probably still prescribing a lot of DMDs. So I don’t know how much of an obstacle this is in MS. Obviously, there are time and personnel costs necessary for participating in trials, but I wonder if the pharmaceutical companies reimburse some of that (maybe?) and academic MS centers (which is a lot of them) seem to be required to do research by their mission. The place I go is actually trying to increase its participation in clinical trials.
Julie pointed out the time commitment to participate in a clinical trial and this is certainly an obstacle. I live 3 1/2 hours from the place I’m in a study which means I have to take a whole day off work for every follow up, even the short ones. I can only do this because I have a very understanding workplace with excellent (for the U.S.) benefits and time off. The drug company has promised reimbursement for travel time, but it’s been over a year and I haven’t seen a penny yet so I’m not overly optimistic.
Another obstacle is the inclusion and exclusion criteria. The researchers get more reliable results with rigorous inclusion criteria, but if the included population ends up being substantially different from some of the population that uses the drug, they don’t really know what’s going to happen to all those people who are older or younger or have co-morbid conditions. For example, historically, a lot of clinical trials were restricted to men and some of the approved drugs turned out to have unexpected effects in women (see http://www.jci.org/articles/view/19993). Minorities also tend to be underrepresented in clinical trials.
I read somewhere that some surprisingly high percentage of people in MS clinical trials aren’t technically qualified to be there. It’s one of those things that I’ll never find again, but I think it applies to me as I’m pretty sure I’m not technically qualified to be in the trial I’m in (although several neuros have since told me to stay put anyway now that I’m in).
Unlike the cancer trials described in the article, a lot of MS trials still have a placebo arm. There has been debate about whether this is ethical. There are some doctors, like Lulu’s, who think it is unethical to put a patient in a trial with a placebo arm when there are treatments that are known to be effective.
I understand that in the early MS trials, the participants tended to be people with more active and severe disease as they were the ones motivated to join trials with potentially bad side effects. This contrasts with current participants, who tend to have much milder disease, as these are the only people likely to be willing to go in a trial with a placebo arm (well, that and people who have failed the other DMDs, but I’m pretty sure I read that current participants do tend to have milder disease). I wonder if this leads to some differences in results.
There have been some trials without placebos where participants either get (1) a sugar pill and real shot of one of the current DMDs or (2) a real pill and an inert shot. I would think that there would be some difficulties with blinding since the side effects from the current DMDs are fairly obvious. I haven’t particularly noticed any side effects from the drug I’m on, but at my last physical, my PCP looked at my CBC (complete blood count) and was trying to figure out how to ask me if I thought I should consider an AIDS test because my WBC (white blood count) was through the floor. He looked relieved when I told him that it was probably the trial drug, which is supposed to keep the lymphocytes in the lymph nodes so they don’t go to the brain and do mischief there (as a side effect, it also keeps the lymphocytes out of the blood). Anyway, I’m pretty sure I don’t have AIDS as I had to have an AIDS test to get into this trial and the likelihood of my having picked it up in the last year is fairly infinitesimal.
Trials without placebo arms tend to be more expensive (they need more people to prove their point and they also take longer because the difference between the groups is less; they also have to pay for the drug for the placebo arm). Here is how the MSRQ article described below justified placebo arms:
“Trials using placebos are carefully considered and must ethically justify the use of an inactive treatment. On the other hand, using placebos requires fewer subjects and shortens the time frame of the trial, enabling fewer patients to be exposed to potentially ineffective new drugs for a shorter length of time. This occurs since it is easier to see the difference in results of an active drug compared to a placebo than it would be to compare two active treatments. The sample sizes often are 4 times as many patients and thus, up to 4 times the cost. Furthermore, by using a placebo, we get a better idea of just what side effects and serious adverse consequences are due to the active drug compared to consequences of the disease.”
There are risks to trial (or any) drugs, even if they try to minimize them. Two people (maybe three) have died in the trial I’m in, probably for reasons related to the immunosuppressive nature of the drug. The newer drugs, despite being potentially more effective, tend to have worse side effect profiles.
I would think that for all of those reasons, MS trials can have trouble recruiting, especially among people who don’t have severe disease and, therefore, have other options. I went to one of those big pharma-sponsored MS talks and the neuro said that the trials for FTY720/fingolimod (which is what I’m in) have been delayed because they’ve had trouble recruiting enough people. Which means it takes longer to get the drug to market.
I agree with PatientX that there doesn’t seem to be enough ground-breaking research. So much of it is incremental and we need something more dramatic. I also think there’s still too much focus on the autoimmune, inflammatory aspect of MS. There’s a lot of talk about neuroprotection, but I don’t see much concrete coming out of it (or maybe I don’t know where to look). Nor do I think there’s enough work on alternate hypotheses or factors, like the vascular/chronic cerebrospinal venous insufficiency idea (which I talked about at
http://www.medhelp.org/posts/Multiple-Sclerosis/Interesting-takes-on-the-etiology-of-MS/show/986162) or HERV (human endogenous retroviruses). Of course, I may be biased, since these neuros keep telling me that the standard immunomodulatory DMDs aren’t likely to help me since I’m apparently not having acute inflammation.
I like this quote from the article, which mentions attacking important problems as a characteristic of successful trials:
“It is not entirely clear why some trials succeed, but researchers say those that do may have some features in common: patients may be like Dr. Fye, with no or few options, so they are easier to recruit, particularly if the drug promises to make a real difference, not just give them a few days or weeks. Successful trials also typically address an important problem, as opposed to a more marginal one, and involve experienced investigators and patient advocates who push for participation.”