McNicholas N, Patel A, Chataway J. It is better to be in a clinical trial than not: lessons learnt from clinical neurology–the management of acute multiple sclerosis relapses.QJM. 2012 Apr 17. [Epub ahead of print]
OBJECTIVE: To compare being on-, or off-, a randomized controlled trial (RCT) for the same intervention.
DESIGN: Patients experiencing a clinically significant multiple sclerosis (MS) relapse, who received a 3-day regimen of intravenous methylprednisolone as an ambulatory outpatient, were compared with a similar group of patients who had previously been treated exactly in the same way while participating in a RCT. The Multiple Sclerosis Relapse Management Scale (MSRMS) was used to measure patients’ experiences of relapse management in both groups. The two groups were compared under four main headings: interpersonal care, access to care, information and coordination of care.
RESULTS: The principal finding was that interpersonal care was significantly worse in the off-trial group (P = 0.0001), implying a beneficial trial effect on patient experience.
CONCLUSION:The effect observed is likely secondary to trial participation; both groups had similar baseline features, and were treated in the same way. Likely mechanisms for the differences are protocol, care and Hawthorne effects. The findings support the incorporation of structured RCT-style practice into routine clinical management, in order to deliver a more patient-centred care in the treatment of MS relapses.
We have always believed that it is be better to be part of a trial than not as you invariably will get some placebo effect even if you do not get the active drug. The Hawthorne effect is a form of reaction whereby subjects improve or modify an aspect of their behaviior being experimentally measured simply in response to the fact that they know they are being studied,not in response to any particular experimental manipulation.
I'm on a trial for RRMS and I would thoroughly recommend it! My neurologist was quick to discuss trial participation with me after diagnosis (5 yrs ago). I said yes (reluctantly) on the advice of a my neuro and a close friend who is also a medic. I was grumpy about the numerous appointments in the early stages of the trial, but in reality I was very very grumpy about the diagnosis! So ANYTHING associated with MS would invoke serious attitude despite it potentially helping me! However, all the trial nurses and docs were/are brilliant and it became very hard to maintain serious grumpness! The MS has been virtually dormant in me and now four years on I'm down to 6 monthly appointments. I subscribe some of my current good health to the trial and have modified both my behaviour and thinking. I think my trial will be abandoned as the drug hasn't performed that well, but I would definitely participate in another trial if possible.
In addition to my post on Hawthorne effect I would say better care is also likely as Bonnie pointed out
What usually happens to participants when a trial is over?
I heard of somebody who improved a lot while on a trial. Turns out ahe was on the actual drug, and after the trial the treatment was going to stop. In this case the neuro arranged for her to continue getting it for free.
The drug is not yet on sale. When it gets approved and becomes available she probably won't be able to afford it
What happens after the trial?
This varies from trial to trial but you point about free drug on trial to paid drug after licence, is problem of post/zip code and how your health systems work from country to country.
We have no countrol on that
Re: "I heard of somebody who improved a lot while on a trial. Turns out ahe was on the actual drug, and after the trial the treatment was going to stop. In this case the neuro arranged for her to continue getting it for free."
Most phase 3 trials now include an open-label extension study in which all study participants get drug. This is for safety reasons.
"Most phase 3 trials now include an open-label extension study in which all study participants get drug. This is for safety reasons."
What are the safety reasons? To get data if longterm use is safe?
Re: "What are the safety reasons? To get data if longterm use is safe?"
Most rare side effects don't occur during the 2 years of the trial so the open-label extension allows for the collection of safety data in a systematic way. For example, the PML risk of Tysabri only emerged in the open-label extension study. Similarly the risk of whether or not a drug increases the risk of secondary cancers can only be answered with large numbers of treated MSers are followed for year.
Ironically, my trial experience was the opposite. I was on the real drug, but so far as I can tell it didn't work (although, of course, that can't be proven one way or the other for sure). I saw a neuro who did an EDSS exam every three months and to whom I could not talk about my symptoms (other than as part of the test) and another every six months who listened to my heart and lungs, but wasn't interested in nor had time to talk about anything. I continued to get slowly worse throughout the trial and felt as if I had been abandoned and left to my own devices. I was told I didn't need regular neuro appointments during the trial. When I did try to bring my frustration up with my regular pre-trial neuro, the neuro's response was there was nothing else left to try if I got out of the trial.
The armory is admitedly limited but
there are new trials comming along all the time.
When on the trial and you feel things are worsening yes it may be because the drugs are not working or it may be that they are working and that you condition would have been alot worse without them.
As Prof G has been talking about expectations recently, the drug may not flatline the disease but slow the trajectory, so despite worsening there is still some benefit. This why controlled trials are necessary and it is great if you can complete the trial
There are good, bad and not so good neuros, visit "MS life" and we hear about it every time