Need for Adaptive Research Designs in Speech-Language Pathology

Need for Adaptive Research Designs in Speech-Language Pathology


>>It occurred to me that when we look at
the history of clinical trials in our field, that this concept which comes primarily from
pharma and from drug trials and also chemotherapeutics for cancer, might be extremely adaptive to
our areas of interests. Because we do not know if we have the optimum treatment to study
before we go into a clinical trial. And really what this does is allow you to determine what
would be the best way to handle your treatment. Now in pharma and chemotherapy, they’re often
worried about toxicity. And so the — what they’re trying to determine is the best ratio
between how much of a treatment is toxic and will kill the patient and how much will benefit
the patient without killing them. So we don’t have that problem in most of our cases. We’re
more concerned about fatigue and other issues like how many times can the patient come into
the clinic and partake in therapy. But so those are very real constraints. They’re not
as dangerous for the patient but they are constraints. And we need to know what kind
of therapy approach and how intensive it would be to try and optimize therapy before we do
clinical trials. So that’s the purpose of this workshop and hopefully by the time we
come out of this we’ll have discussed some of the trials that have already been done
and we have some of the top rate researchers here. Susan Langmore, Joann Robbins to discuss
some of the big trials that they have done in swallowing particularly. And so we’re going
to be sort of an informal workshop here but we all do have presentations. So I’ll start
on the first one. So those are my disclosures. I get some research support from Passy Muir.
I have some patents that if I live long enough I might get some income from. And I receive
some NIH grants. Now one of the concepts of this started when I did a review last summer
for a journal and they wanted us to discuss what had been done in the last 2 years in
clinical trials in dysphagia. And they wanted me to address non-swallowing tests and swallowing
tests. And this turned out to be a different kind of study than we envisioned. We thought
this would be a snap. How many clinical trials are there anyway? And we had quite a surprise.
There were quite a few random controlled trials in a 2 year period in dysphagia. We started
off reviewing everything in the literature. And I don’t know how — do you see an arrow.
I don’t see an arrow. Okay. We started off reviewing — whoops — everything in the literature.
Then we honed it down to what were clinical trials or controlled clinical trials where
they didn’t have random assignment. And we ended up 3 batches. The yellow batch over
on the left which was 1 trial where people did just swallowing therapy. In fact, in this
case, the Mendelsohn Maneuver. Another where they indirect therapy. That is some other
therapy that wasn’t directed towards swallowing and then a third where they combined direct
swallowing therapy. Oh thank you. Wonderful. Combined swallowing therapy with another indirect
therapy. And I’ll explain to you these indirect therapies or either brain stimulation such
as transcranial magnetic stimulation or direct current stimulation. And in this case, just
that was provided in these kinds of studies which are 16. So this is clearly where the
field is going. They combined transcranial magnetic stimulation while the patient is
doing therapy or direct current stimulation while the patient was doing therapy. And you
can see that we had 1 random controlled trial. One random controlled trial here and 1 controlled
clinical trial. Five random controlled clinical trials and 4 controlled clinical trials. Well,
we looked — we used their data and computed effect sizes. And if you compute the cones
D, the general understanding is no effect is down at .2. You get a small effect between
.2 and .49. A moderate effect between 5 and .79. And then a large effect size is something
like .8 where it’s close to a standard deviation in the data that you’re getting a change of
therapy or a treatment. And when we looked over these random controlled trials, we found
that the effect sizes for behavioral therapy alone were very small, .3 to .4. The effect
sizes for other modalities were a little bit higher but not huge, .45 to .8. This is like
repetitive TMS, deep brain stimulation, icing, or levodopa. And these had moderate effect
sizes. When they combined dysphagia therapy with these other therapies such as direct
current stimulation, video feedback, or neuromuscular stimulation plus swallowing therapy, the effect
sizes range some were low. Some were 1.2 but many of these were studies during the early
recovery process and stroke, and you can see that in their sham group or the controlled
group they had an effect size of 1.2 which is huge compared to the therapy. So it’s drowning
out the therapy effect size. So in this review we concluded that the effect sizes are not
overwhelming. Swallowing alone was low. Other therapies alone were moderate — small to
moderate and then combined therapies had a much better range but compared to spontaneous
recovery, they’re not overwhelming. So this suggests that we need to have optimized therapy
before we do clinical trials so that we get the best that we can possibly can before we
start comparing different treatments. Now, in all of these studies, surprisingly, everybody
used a very similar regimen. They used an infrequent and short regimen in that the patient
was seen 1 hour a day for 10 days or you know, the weekdays during 2 weeks. So that gave
them a total exposure of 10 hours and during that time, they could do as many as 600 swallows.
Outpatient rehabilitation was even more infrequent and there, the dosage was — well, the duration
of treatment was 2 to 4 but they were only coming in 1 hour a week. And had an exposure
of 6 hours of therapy to try and change their swallowing. So we need to consider other regimens
to try and optimize the effects of our therapy. And one might be prolonging the therapy. Another
by multiple sessions a day or shortening the therapy to avoid fatigue which is our adverse
event. Combining other modalities while you’re doing the therapy as well. And adaptive designs
allows us to examine each one of those parameters and find out what would be the best way to
deliver the therapy and what would provide the most bang for our buck, so as to speak.
We need to find out how many trials a day a patient can do. What the most effective
session duration. Why is an hour always used? Maybe some patients that’s too long. Finding
the most effective treatment dosage in the total number of sessions. So we want to look
at curves where we change, get the effect size for different numbers of sessions per
day. Perhaps 1 session isn’t the optimum. Perhaps we need to do 4 or 5 sessions a day
and we get a better effect size with that. Another is the session duration. These are
hypothesized curves. Maybe 15 minutes is better, 16 minutes is not. So we need to be able to
examine those aspects. And then, how long should therapy be? Maybe 2 weeks is not best.
Maybe we want to get further up on the curve and try and get a higher effect size for a
longer duration of therapy. So where would we use adaptive designs? Before
we do the large random controlled trial. They can help us identify optimum treatment regimen
and avoid a costly lengthy RCT with a not optimal, effective therapy. Maybe different
regimens for different types of patients or different treatments for different types of
patients and those can be examined as well. But I should warn that all of this needs to
be done very closely with a bio statistician and we have invited Dr. Yates to present to
us on this type of design. And how it can be used. And she will help us translate some
of this from what’s used in other areas of research for clinical delivery to our area.
So, Dr. Yates it’s with great pleasure that she had accepted our invitation to come and
present to us today. So thank you for coming.

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