Transcripts from Jean-Paul Collet's talk at
The International Conference on Cerebral Palsy
May 2nd, 2003 in Quebec City, Canada
0:00 Welcome to the session on intervention strategies.
Our first speaker is Dr. Jean-Paul Collet. He is a paediatrician and associate professor at the department of (noise) at Mc Gill University. There he is director of (mot inaudible) epidemiology program. Dr Collet is the director of the randomised trial unit and director of clinical research at Samy Davis Institute the Jewish hospital.
Recently, Dr. Collet took the direction of the provincial program to promote clinical research and increase academic research quality. Dr. Collet has published over 100 articles and has supervised many students. He has been invited numerous times to give presentations which has discussed methodology and new trial committees.
1:10 (Inaudible) lessons from the trial. That the trial has treated people and has been published two years ago and I think everybody knows the results so I won't spend too much time ''commenting'' the results but talking and sharing with you euh you know the... all the experience that we gained by conducting the trial and (inaudible) body (inaudible) and societies.
1:42 So we start now by at the seating committee with an executive committee and was also helped by a (inaudible) committee and a scientific (inaudible) committee that was (inaudible). There was also a (inaudible) that was checking the trial on a monthly basis during ''for the child''.
2:08 Just briefly, there was two treatment, one was hyperbaric treatment with 1.75 atmosphere of pressure and 100% oxygen that give 1253 mm of mercury of PAO2, while the comparison group was a slight pressure 1.3 atmosphere with air and that gives 128 mm of mercury in in the blood, so the difference in term of blood oxygen was extremely important between the two group.
2:44 And the results very simple for the GMFM score, this a global score, we can see that the two groups improved by about 3% with exactly the same amount in the group the green box is placebo and the yellow box is the hyperbaric treatment.
3:05 And this is a three month euh (noise) without without euh treatment because there was an evaluation after 40 session and another one three months later.
3:17 We can see that the amount of improvement was gained after 40 treatments remain stable three months later.
3:25 And this is true for every sub-scale. euh you can see that there is nothing significant only one was significant it was ''sub scale'' E, in favor of the placebo group. And three months later it is the same thing. So there was euh no effect,
3:45 and you can see also that in term of the important of the improvement 25% of children in each group improved by more than 5% which is considered to be euh important. So one quarter of children improved in a substantive manner during the trial.
4:10 For the (inaudible) it was the same thing, we found improvement I just show you this one at three months was with a big improvement in both groups euh and a little bit better in the placebo group but nothing euh really important to consider.
4:30 The main results therefore was that participating to the study improved the children scores as well as other outcome because I did present the neurological improvement in the scale memory, cognition, and also the speech but there was also a slight improvement in both groups.
4:53 There is a presentation today by Maryse Lassonde a little bit later this morning about the psychological development during the course of the trial.
5:02 But it was an improvement in euh both groups euh independently from the intervention. Hmm the this improvement were important and there was no difference between the two.
5:20 And the question was why, we do not know (noise) and the were just hypothesis. The first one was that the two interventions were equally efficient and people do not favour this one but euh ''but a separate hypothesis'' not the first one
5:37 the second that was recommended by the scientific committee and by the community in general in fact it was the effect of participating into the trial
5:47 and euh it was a placebo or learning effect because by looking in the test you know you can improved it by learning how to do that better
5:57 and it could also be normal development although the follow-up period was short enough to ''prolong warranty'' it couldn't be a big improvement in the (inaudible) in fact the conclusion was that very likely it was hypothesis number two that's in fact participating in the trial with all the stimulation involved in the trial was responsible for this effect.
6:23 So this this is conclusion that was presented (inaudible) three years ago illustrating the results.
6:32 So now after the trial, the situation was not very easy, (laughs) (inaudible) understatement,
6:43 In our groups in Quebec, some parents did not like the results, they did not believe the results they said that the authors were paid by the government to find negative results
6:59 It was extremely hard ... very difficult because as a researcher you really try this in an ethical (bla bla inaudible) dependence and not ready to any pressure in your back and we had (inaudible) no pressure and you try to do good and when you're accused to do bad, its its not easy.
7:18 Euh other parents because I got tens or hundreds of letters from different parents in different countries asking for the opinion because they were hesitating about sending their child to undergo hyperbaric treatment and we could mention the article and discuss with them but they were a little bit it was not because of them but because of all the controversy that was supported by many physicians that ''were in fact finding'' the treatment and were criticizing the articles and criticizing also the authors,
7:59 I was accused of being paid by tobacco companies and
Pharmaceutical companies not tobacco !
it was .. I am (inaudible) all of the mention that (inaudible) by this group of people.
8:10 Euh and the hyperbaric center is in fact is not a good practice because there was no regulation, and I wanted to prevent them to practice.
8:18 So that was the situation in summary
8:23 So what happened in the next (inaudible)
Even that is to share the experience about the trial and of also two other things that can be interesting for the view who are doing research in physiotherapy. because and also for the model of evaluation that could be taught about this experience.
8:43 Now for the trial I say yes we could improve the trial. In fact its not really improving the trial because the good part, and I think we can the team can be all proud of (inaudible) in this trial because it was euh I mean the trial was good and even if people try to denigrate the results and to do hard analysis, it could stand, and was published in the Lancet, it was a good study.
9:13 Very important (noise) by providing the minimum intervention, it was euh at one time their was a choice and it was discussed in the committee the two options would be to have a complete placebo without treatment,
9:33 or to have a minimum treatment which is a slight hyper pressure with air that could help blinding people but of course the intervention is not totally neutral because there is a slight intervention.
9:46 And at this time, during the course there was a consensus around the table with all participants even with all that were strongly in favour of hyperbaric treatment
9:55 to say this type of neutral intervention is not likely to produce any
10:02 And given the fact that the expectation and euh the (inaudible) and all the the mental strength created by what you expect from the results is probably the strongest compromise to explain the chance that for cures especially when you are assessing an outcome which is a score of performance.
10:28 It was really important to blind people, because the performance with people is likely to be different by their knowledge about the intervention they receive. So in our study, I think the strength of the study, was not on the all the data management procedure and the evaluation process that's gonna (inaudible) and standardised which was also left to keep people blind from the intervention.
10:54 A scientific committee was extremely useful, and euh a good committee I think helped many physicians to be clear when they are talking with parents about recommending or not to go to hyperbaric.
11:08 So this a good part and I think we would do it again the same way. We would change I think euh the trial regulation, trial administration and we will increase euh, improve communication.
11:25 And here, just to remind you, I was involved in this trial as a methodologist, but in fact I was not working in this field specifically
11:36 euh and I was involved because the promoter of the trial was also owner of a hyperbaric chamber in in Quebec and it created a feeling of possible conflict of interest and we wanted to dissociate euh people that had generated the idea from the people who would conduct the ''agence'' its why as a methodologist I was responsible for running the trial.
12:01 And euh so I came ''what to'' be at the end, and also I was not aware or I did not catch euh you know euh .. quickly enough the the situation. The situation is that I'm going to describe four problems:
12:15 The first one is that most participants were biased and in favour of hyperbaric treatment (rires) (inaudible) come to do an evaluation, they were coming to get a seal of approval in order to be reimburse when they have access to hyperbaric treatment.
12:31 So it was just the the obligation to do to a trial in order to satisfy the regulation and get treatment approved by the Quebec euh reimbursement system.
12:45 So there was no (inaudible) there was no (inaudible) balance, they were already convinced.
12:51 So if (inaudible) had to do it again I think we will spend a lot of time to discuss with the parents all along the trial, to discuss with them about the principle evaluation and about the placebo and euh spend enough time to to to put them in fact of the context of doing an evaluation and not a certification.
13:12 We would also challenge the physicians in term of their conviction in order to minimise the impact they may have on this population. Euh I mean to give the very physicians that were strongly behind these (inaudible)
13:30 And also to keep track in writing of very important decisions because when you make a decision it should be officially discussed, the statement that would then become something to which we could refer if we need and you know we said that at this time (inaudible) ...
13:50 And the (inaudible) would be to create a state of mutual (inaudible) and to have the current (inaudible) for in the evaluation.
13:58 The second point is (noise) committee. At the beginning, when I took the project was lead by the physicians who were in favour of hyperbaric treatment and it was made of friends you know it was a large group of people.
14:12 So (inaudible) committee and were all in favour of hyperbaric treatment.
14:17 And one of my mistake is that I kept the same committee and I added three other methodologists, statistician, clinical trialist. And that was (inaudible), because at the time, at the end, at the time discussing the results, euh It was not neutral, and absolutely not representative of the scientific community, it was in fact a group of friend, were in (inaudible) of hyperbaric treatment, and two of the people who were the bad guys saying no there is no results. And in fact (inaudible) and at the end the parent who are looking that we knew that it the committee, there is majority of people who are in favour of hyperbaric saying that there is an effect.
14:59 And in fact, you are sampling all the scientist in the province at this time, you would find probably the same people convinced they were all in the committee, they were not in the committee.
15:12 So it would have been much better to reorganize the committee (noise) to start (inaudible) with a new group and (noise) (inaudible) this is what I say here. And euh and also it was patients representative from the CP community, and because the patients representative in our group were patients representative all the groups that went in the trial
15:36 So again there were variance and one patient representative (inaudible) spent over 30 000 dollars in hyperbaric treatment for ''one'' child, so euh its very hard to be neutral again and when you have (inaudible) this commitment and spend this amount of money.
15:57 And also to use a committee as our communication barrier because when the committee become independent then it is neutral and representative euh then they can now intervenes the ''porte-parole'' to can bring the originals and the decisions with the (inaudible).
16:19 (inaudible) after, this is point number three, where the money was coming from the government and euh we had no contact with national CP and international CP societies and that was a mistake again, because it was (inaudible) paid by the government and (inaudible) the results.
16:45 Point number four is that ..euh When the results went to the publication and discussed with (inaudible) in the community, they were accused that there were no good reason except that euh again there was no official position from the different societies.
17:04 And euh and then it creates a little bit of difficulty because you have activists on one hand that have you know not really fitting them as structured as they are and that's the real problem not only in this specific situation in autism and vaccines at this time is facing activists in court.
17:25 So the (inaudible) to that it's the individual right to choose customer treatment, with (inaudible) treatment, the role of clinical research, researchers, scientific societies, (inaudible) and also what to do with activists. (rires)
17:42 All discretions (inaudible) because that's the real issue in our society, everyone has the right to to talk, and this is democracy and we like it strong but we have to be ready to play the role in a democratic country in order to provide our answer at one point.
19:31 Now to another aspect which is also a lesson from the trial that on the methodological aspect. I found that evaluating euh the outcome in children with cerebral palsy is extremely difficult and euh, I show you a different study between lines to show that (noise) new (noise) improvement in CP, in children with CP, and this is equal in movement, there are 8 plus at 7 %, and and the improvement is somewhat similar to the type of improvement we find in our study.
18:39 And euh expectation (noise) is certainly a very important compromise, because again its every time it's a score of performance and performance is influenced by the expectation and the motivation.
18:54 Euh there is possible change of collaboration with (inaudible) and gives a collaboration is chanting the performance with be as good or it will or it will improve, the collaboration improved.
There is a learning effect that we discussed, ''regulation'' to the mean which is also possible if the baseline is not stable, artificially high or artificially low for any reason. And again performance means that the baseline can be wrong at that in the beginning. And (noise).
19:26 So euh this is why I think in all this study there is a need for having a control group. I think there is a need for randomizing patients and also blinding. If blinding is not possible, there is a need for independent assessment, made by people who are not aware about the type of intervention.
19:46 And its treatment (inaudible) procedures and need stable baseline assessment in the beginning. So in that situa... its right difficult topics and very difficult domain for doing research.
20:02 And euh and I finish by that, because we are in a situation under where we taught about expectation regulation being responsible for the improvement, so now we could discuss the placebo effect because people call that in negative way ''it is placebo'', ''it is psychological''
20:18 but we could think about promoting this placebo effect and now we falling to be out the domain which is euh euh you know very often ''caught up'' by complimentary medicine.
20:29 With whom Mary Law this morning talked about family center approach which is probably including this type of activity. But if we think about euh it's euh a good placebo, it could (inaudible) be think about the mind strengthening and improving in fact the global test of the child by acting at (inaudible). And that's a very interesting issue in this specific domain because euh I think we'll pass about that.
21:02 This is, this is normally what we expect in the 1 minute euh the the environment, especially in cerebral palsy has a strong effect on the body and responsible for disease which is a limitation during an evaluation.
21:18 The mind is here and related to the body and all the quality of life and mood and things in between because it's really a combination of the two together.
21:28 And spirituality is something which is more or less (inaudible) but not quite its very tough and nobody can working about that.
21:37 This is in general, if we talk about all approach in society which is more mechanical in modern science euh the body genetics plays a very important role then again in CP, environment is a strongly important factor.
21:55 Mind also exists but the two domains are totally separated, physicians for the body are different than physicians for the mind. Psychology, psychotherapy and very often they do not talk to each other.
22:08 That would ''to be in favour of the'' environment for the mind like the family we don't know very well how to deal with that and the interaction is a big interaction model between the mind and the body. So euh its its euh it (inaudible) to be fragmented and not very efficient.
22:23 The holistic approach, and it doesn't mean necessary other type of medicine,
it can be hard to seek one approach and type ''
it can be done in our medicine.
22:34 You have also the body, the mind and spirituality but more important it is the interaction between all these boxes which is important and that euh euh this in charge (inaudible) harmonious whatever level of the body you can find harmony, that's the message. Then when it is harmonious or disharmonious then there is psychometic diseases, depression, stress, anxiety but also (inaudible) so it's a very different approach. But to do this type of study you need (caugh scuse me) euh also to provide the evaluation to assess this overall aspect so its not an evaluation which is fragmented, piece by piece which which is in fact evaluating the overall aspect. So in conclusion, I will just repeat that and I thank you.