Tuesday, December 23, 2008

Speakers at IFA 2009

The list of the key note speakers of the International Fluency Association (IFA) congress in Brazil in August 2009 is public: see here.

Claudia de Andrade: The familial profile of stuttering

(Department of Physiotherapy, Communication Sciences & Disorders and Occupational Therapy, University of Sao Paulo, Brazil)

Elizabeth Harrison: Technology in stuttering treatment for children and adults

(Department of Linguistics, Macquarie University, Sydney, Australia)

Luc De Nil: Multiple facets of stuttering: Insights from brain and behavioural research

(Department of Speech-Language Pathology, University of Toronto, Canada)

Suzana Jelcic Jaksic: Comparing the needs of consumers in developing and developed countries

(Children's Hospital, Zagreb, Croatia; ISA)

Registration for talks and seminars is February 28th, so you still have time to get your proposal done. I am not sure whether I will attend or not. It is a lot of money to go to Brazil, and I am self-financed. I probably decide in the last minute, as usual.

Luc de Nil is the only scientist talking. He is a professor in Canada and has done a lot of brain imaging research on stuttering. He will talk on brain and behavioural research. Certainly his brain research is interesting; his students and research staff currently look at dual tasks performance in stutterers. However, I am more sceptical on the recent research on temperament which he supervises; I hope he is not going in that direction in his talk. Then, we have Elizabeth Harrison talking on technology in treatment, which could be interesting. However, I hope she is not diverting to Lidcombe outcome research on which she worked and which she not convincingly defended in an on-line debate I recently had with Susan Block: see here.

Monday, December 15, 2008

Bad Google

According to Leys, google refuses to block adverts with cure promises for stuttering. Though having read his emails to google, he could maybe have been a bit more diplomatic:

Following various email exchanges over the last two weeks, Google have today announced that they will continue to allow advertisers to claim that they can cure or eliminate stammering.  For example, one current Google AdWords ad reads ‘Breakthrough cure takes 9 minutes - 100% guaranteed - eliminates cause’.

As the root cause of stammering is a neurological condition, it is not possible to 'cure' stammering, in the accepted medical sense of the word.  So, whenever they say this, Google advertisers give false hope to those who stammer, and give people who don't stammer the false impression that stammering can be cured very easily.

Respectable healthcare companies carry out independent trials on large numbers of people, over long periods of time before they are allowed to claim any kind of benefit for their products or services.  It should be the same with stammering.

Google AdWords have a general policy against what they describe as 'miracle cure' advertisements.  But, although they check the wording of ads submitted for ‘specific diseases such as cancer, AIDS, psoriasis, arthritis, fibromyalgia, cystic fibrosis, multiple sclerosis, leukaemia, bipolar and schizophrenia’, they do not do so for ads claiming to cure other conditions.  Thus ads which claim to cure stammering will still be approved to run.

Google say that their terms and conditions make it clear that all adverts must not violate any applicable law, regulation or code of practice (including the Committee of Advertising Practice Code in the UK, which is enforced by the Advertising Standards Authority).

These kinds of ads, however, clearly DO violate the UK CAP Code, because the ASA have already taken action successfully against one advertiser who was claiming to cure stammering - and is keen to act against others.

Unlike most advertising mediums, Google take no responsibility for the content of the advertising they feature.

Earlier today, I replied to Google, asking to arrange to speak directly to their Policy Team.

I then emailed the Stuttering Foundation of America and the NSA to let them know the situation.

I then reported Google to our Advertising Standards Authority.

I have also contacted various journalists who have been kind enough to support our campaigns in the past.

Friday, December 12, 2008

It started with a whistle

Apparently, Orangutans are able to whistle voluntarily leading to speculations that it is a precursor to speech and language: see here. Maybe early humans first started to whistle, associated a piece of information to a specific whistle, and created their within-group set of whistles. At some point, different whistles were combined to form sentences and language. First, speech was just whistles and all attention was on the whistle: so you have a thought you want to communicate and then you whistle it. Then speech production became more complex and thinking and speaking happened at the same time, leading to automization of speech. You do not have to focus on speaking but just think and it comes out automatically. And stuttering is a problem with this automatism. So first were the whistles, and when humans stopped whistling they started stuttering! ;-)  (Though, I have to admit that I am a bit puzzled why we don't still whistle our speech if the speculation is correct. We could do that, no? Maybe it is not possible to create as many different whistles as we are able in our human voice?)

Vancouver Film School Documentary

Check out this well-done documentary movie on stuttering by Vancouver Film School students through the following VFS production program:
Director Bruce Oothout
Director of Photography Shane Smith
Producer Youssef El-Khoury
Editor Raymund Santos

Thursday, December 11, 2008

Political correctness madness

A writes in response to my last post:
This is a horrible idea. It frustrates me to no end that people think that stuttering is something that you can "overcome". To add a competitive edge to it will make those who feel a great shame and pain about their stuttering feel even worse. The movement should be towards a greater acceptance of stuttering in the society. Not changing the stutterers to fit the society's expectations of "normal" speech.
A's statement is a good example of the political correctness madness that distorts current day thinking.

First of all, A asks for greater acceptance of stuttering in our society, when in fact he or she is not even able to give his or her real name but chose to remain anonymous! A puts me down for thinking the politically incorrect, when in fact I do a million times more about greater acceptance and transparency of stuttering by putting my life (including my stupid picture :-) and thoughts on the Internet. Everyone can read my blog including future clients or employers.

Second, I refuse the notion that we are helpless victims of a bad society that puts us down (blame-it-on-society syndrome) and creates the handicap that we experience. What non-sense! The vast majority of people only want to help us, but do not know how. In fact, we do not even know ourselves! Yes, there are some who might laugh or not be accepting of our handicap. So what? Is such behaviour so special? No it is a generic feature of humans. People (including and especially stutterers) laugh or are not accepting of all kinds of things: political attitudes (he is a neo-con republican), beliefs (he believes in the bible), weight (she is really fat), height (he is so small), beauty (she is really ugly), social status (she is white trailer trash), and so on. And yes there are discrimination in the job market. Why? Because stuttering does not help business. So we need to convince our employers that we have compensating strengths or that stuttering is not relevant to the specific job. The same is true for small people, dumb people, over-weight people, and so on.

Third, A seems to imply that somehow society creates stuttering. I say: Complete Delusion. Our genes and other influences have caused our stuttering in the first place with or without society. And we all feel a physical handicap with or without society. We cannot say what is on our mind all the time like a child without legs is restricted. It is not imposed by society, and it is physically experienced. Society reacts to the handicap, and its reaction is to 95% determined by our reaction to society! It reminds me of the talk shows with obese people who say things like "I want people to accept me how I am", "I am happy who I am", and "men find big women sexy", and of course it is society that makes us feel bad. Come on. The vast majority of men and women who are overweight hate it and want to be slim. Not because society wants them to (though it adds pressure), because they want to because you have restricted body movements, you are always out of breath, you have a very restricted sex life or none, diabetes and so on. They are deluding themselves: "I can't loose weight and now I just tell myself I actually feel good about how I am". I am not going to say that I feel good about stuttering, because I do not feel good about stuttering because I experience a physical handicap. What I can say is that I acknowledge that I stutter and that the propensity to stutter will stay with me for the rest of my life. And I also do not accept that I cannot improve my speech. I can if I work on it.

Fourth, the movement should not be about greater acceptance, but about greater knowledge about stuttering. I am not sure it is healthy for society to accept us like we are; should be accept overweight people to be overweight? I do not think so. We should help everyone with a handicap to improve as much as possible and educate others about the handicap, but how can I say something is OK when it is not OK. My speech is not OK, I cannot say what I really want to say. (If I only stutter slightly but say exactly what I want to say, then it is OK for me personally.) I am just deluding myself if I say it is OK. Not a single person in their right mind will listen to stuttered speech and say: Well that's OK even though they might publicly say so. I want them to think: "That's not OK, but it is not his fault. He is a person with strengths and weaknesses of which stuttering is one. I admire his courage to live life despite his handicap and if I can help him to improve, I will."

Wednesday, December 10, 2008

We need more competition!

Becoming more fluent is hard work over a longer period. You can also say that becoming fluent is like achieving mastery in a sport; the skill of controlling our propensity to stutter. How do you become a top tennis player at your local club? You need to be focused, live in the right environment, have spare time, be motivated, have a competitive spirit, some talent, receptive to coaching and ability to practise regularly and hard. For example, I am a strong tournament chess player and spent hours and hours playing chess. Much more than I ever spent on treatment. Is it no surprise that I am not a master in more fluent speech? Why did I not spend more time on stuttering? I would happily be the worst chess player ever for stable fluency.

I guess one reason is that the rules of chess are laid down. You know what you have to do to win, and you know what you have to study to become better. And most importantly, you have constant competition. Other people are challenging you, and I do not take it well when I loose after a hard fought hour-long game! It motivates me to get better and beat my opponent next time! And I know just how bad I am, and no therapist putting on a positive spin. In stuttering treatment, there is no competition. There is no declaration of a win or a loss; you have to make the judgment call.You have only yourself to fight against, or if you wish against the unknown enemy that makes you stutter.

Maybe we should establish a stuttering league where stutterers can compete against each other. In speech, reading and debate contests. We could also have a first-block-out competition. Two people are talking and the first who stutters looses. Another competition could be the-best-secondary-symptoms contest, but I guess that's a bit counter-productive. Well, we can just change it to the-best-simulated-secondary-symptoms contest, and that it is about voluntary stuttering. How about establishing a rating system? So if you win, you get extra points, and the more so the higher rated your opponent was. We could even have national teams that compete against each other. How about club names like Stuttering Sox, Stuttering United, Real Stuttering?

I tell you already you now. If you ever compete again me, you will loose! I am the best! ;-)

Tuesday, December 09, 2008

Connectionist modeling for stuttering?

I am currently doing a postgraduate Open University course on Exploring cognition: damaged brains and neural networks. The course explores two methodologies to study the brain: case studies on damaged brains, and connectionist modeling. We learn much more about the brain when it does not work properly as opposed to when it works well!

Think of your car. After any breakdown be it the battery or gears, you know much better how the damn thing really works! Or go back to the pain and handicap from your last toothache or back problems. Now you really know what and how teeth or backs do every single day. Stuttering is no different. A speech scientist should see the disorder as a blessing. Any scientist who claims to know how the brain speaks must be able to explain why the brain does not speak fluenty for some people. In fact, stuttering is key to understanding normal speech production. If we know why we stutter, we also know much more about the normal brain processes underlying speech and related activities.

The second methodology is connectionist modeling which models brain processes by constructing mathematical models that mimic features of networks of neurons and "injures" them to see the effects. I do not know of any group working on this topic in stuttering. I vaguely remember Pete Howell, professor at University College London, trying to get a group in connectional modelling to work on stuttering. The Boston group around Prof Guenther does mathematical modeling, especially his PhD student Oren Civier: see here. However, they use the differential equations approach which is a very different modeling technique. Ludo Max has worked on models together with them, but I think they agreed to disagree on the right approach. Within the research community their work is completely ignored, simply because no-one understand what they have done or are doing! It took me some time to understand what they have done, but I would need to play around with the equations myself to give good feedback on the usefulness of their models. My intuition tells me that the models are too simple to capture the essentials, and that even if a model reproduces the essentials of stuttering, it does not necessarily imply that it is implemented in the brain in this way.

Tuesday, December 02, 2008

Easier said than done: what makes someone implement change?

What makes someone change? Here, I might align myself with the soft thinking side of many therapists. Science says relatively little about what creates change in a person. I have seen this documentary on this slimmed-down woman who lost 30 kilos and has kept her new weight ever, for several years. The journalist asked her: So what has made you change? She said that she was on a hike and just couldn't make it up the hill without constant stops. And at that moment she swore to loose weight by keeping on walking up this hill every weekend until she can do it without stops. And she never stopped pushing herself, and her weight dropped slowly. She also said that it was not about the diet because any sensible diet will work: eating a bit less, a bit more healthy, and exercise more and keeping it at this pace for ever will do the job.

What creates such a moment that sets in motion such a change? I am not sure. But it is not about that moment. That moment is only the start, the first spark. If you do not have the dried-out land with a hill next door, hiking- friendly social setting, competitive attitudes, friends with similar aims, no life-changing events like death of partner, the right genes, the ability to change quickly, right personality traits, and tools like sensible diet, the spark cannot live on and create a fire. You cannot model such behaviour in a sensible way in the same way as it is difficult to predict revolutions, wars or economies. 

So how can you as a therapist induce change? I have no clue. I fear that the answer is that they cannot. Maybe induce the spark, for who is not excited about starting a potentially life-changing treatment. But will it light the fire? Only the patient can. But actually not even the patient can. The time and place must be the right one. And then the right spark at the right time will light it up. However, therapists can help in that they create treatment that requires as little change as possible to be successful. Like a pharmaceutical treatment. Or improved behavioural therapies.

Monday, December 01, 2008

Therapy is an implementation issue

How do you win the 100 meters? Run faster. How do you become slim? Eat less. How do you pass an exam next time? Study more. How do you stutter less? Speak slower, avoid secondary symptoms and make more pauses. The issue is not in that we do not know what to do, but in us not being able to implement what we should do.

Thursday, November 27, 2008

Live from ASHA

StutterTalk.com has broadcast from ASHA: see here. Listen to the first 15 minutes. It reminds me of giggling teenage girls. A brilliant snapshot of the atmosphere in which therapists interact. Laden with the following commandments:

  • do no criticise your colleagues
  • always praise your colleagues
  • always accept everyone's ideas (even if wrong)
  • never publicly admit that you have made a mistake
  • we are all a big family of friends
  • smile, smile, smile, smile, smile, smile, smile, smile, smile, smile, smile, smile.
  • displeasure is shown by a shorter-than-usual smile

These taboos cause discussion rounds with most therapists to be completely and utterly useless unless you talk to them one on one! And filters through to research and debate on research. There is this immense strong emotional desire for harmony and peace (though if you know them personally, you realize that many don't like each other and bitch all the time! :-). Listen to the first 15 minutes again. Not a SINGLE CRITICAL THOUGHT on their own work. Their sentences contain virtually no information. Their workshops are brilliant, wonderful, I have learned so much, exceptional experience, I was so lucky to have X, amazing exhibition, so valuable, though i am confident of my skills I learned so much more. Let's do the reality check. Let's now compare what people who stutter write to me in tens and tens of emails: I am still stuttering (that's like 95% of emails), I am desperate, speech therapy was pretty useless for me, she saw me fluent but then my stuttering came back, and the only thing she did was smile all the time.
As I have said many times before, this atmosphere of forced harmony and peace is counter-productive to real constructive debates, because therapists are scared to speak out and from the beginning as students their brains are forced into into intellectual schizophrenia as it has to spend 99% of the resources in adhering to the prevailing social atmosphere (what should or can I say in this situation, how do others expect me to react) instead of speaking out (what do I think and what do I feel)
And regarding StutterTalk, from now on I call them the Larry Kings of stuttering. Whoever you are, from saint to dictator, you feel comfortable in their interviews, and leave with your world view intact!

Tuesday, November 25, 2008

Learn more about our brain

Looks like an interesting website on the human brain: see here. Sorry for the few posts, I am preparing an exam with 3000 pages to learn and understand...

Thursday, November 20, 2008

Two types of genes?

I have spoken about my view before, that stuttering might well be a two-phase disorder, see here . Adult stuttering is the result of causes that lead to onset of stuttering and causes that lead to non-recovery from onset of stuttering. Maybe this structure extends to genes. There are stuttering genes and there are recovery genes. Put yourself in nature's shoes, you have all these early humans stuttering and it affects survival rates. Nature can either select out the bad stuttering genes, OR it can select in good recovery genes. If we assume stuttering is only genetics, then from 100 babies 5 have the stuttering genes, and 4 have recovery genes, which leaves us with 1%,  the adults who stutter. The picture is of course more complicated, because it is not 100% genetics but you get the twist. If this dynamics is dominant, the search for genes will be more complicated, because currently the trait is adult stuttering whereas the trait should really be ever-stuttered-as-a-child.

Wednesday, November 19, 2008


The American Speech and Hearing Association (ASHA) holds its annual meeting End of November: see here . It is a very big conference, and a small part of it is on stuttering. I never went. Too expensive for a non-member. I was unable to get the program from the web. If you can find it, let me know!

Saturday, November 15, 2008

Myth Creation

This cartoon illustrates well myth generation and it is no different in stuttering research. Through subtle changes of findings, summarizing of findings, and discussing based on these derivates, the story changes. Whenever you hear any statement, try to follow it back to the roots and you will be shocked to see that in 99.99% of all cases it is far more complicated. The absolute climax in my life was when I asked a therapist on the source of a claim and she referred me to the British Stammering Association (BSA). And I suddenly realized that as a member and chair of the BSA research committee I/we were actually her source of something I never heard anyone in the committee claiming let alone believe in!

Friday, November 14, 2008

Obama a stutterer?

Obama is at best a marginal stutterer. He just has a tendency to use fillers when he is under stress or tired. Maybe his brain is slower to give him the words he needs and so he uses fillers. He just has to train himself to slow down a bit, and I think this is what he has done recently. What is your opinion?

(Thanks for Dave for the tip).

Blog from research team

The research team at the Brain Imaging Lab of Columbia University, New York State Psychiatric Institute, had an interesting new idea, namely to create an Internet blog which aims to inform and recruit stuttering adults and children for brain imaging studies and reporting on its findings. I have already written this post on them. It is always great to have new independent team working on the neurosciences of stuttering, and please if you live in the area get in contact with them and get them in touch with self-help groups.

Monday, November 03, 2008

Did Dracula stutter?

I will be in Romania from Thursday to Sunday visiting Timisoara, Sibiu, and Brasov, and checking out whether Vlad Dracula stuttered and whether being impaled does really make you more fluent. If you are living in the region, let me know and we can meet up.

Good initiative

I 100% support Leys Geddes' initiative to fight claims of cure without any substantial evidence. (Though I still disagree with his early intervention "cure" claims! :-) If you know of any such cure claims, please send Leys or myself an email. Please also check out my Crackpot Posts highlightening similar issues.

Hello, Tom


We’ve all seen ads claiming to cure or eliminate stuttering. But as my company does a lot of consultancy work in the UK, in healthcare marketing, with big companies like GlaxoSmithKline, I know that the words used in advertising, and particularly in healthcare advertising, are normally very carefully written and policed.

So my feeling for some time has been that any organisation which claims it can cure or eliminate stammering gives false hope to people who stammer and gives people who don’t stammer the false impression that stammering can be dealt with quite easily.

Not only is the word ‘cure’ not used by speech therapists, but also it is not used in any other form of healthcare advertising, for any other condition, of which I am aware. No company, for example, is allowed to claim it can ‘cure’ even something as simple as a cold.

We had a Trustees Meeting of the BSA in the summer and discussed this issue. It was agreed unanimously that I should contact all the UK advertisers who are making doubtful claims and ask them to reconsider. If there was any disagreement, I would then refer them to our Advertising Standards Authority who, I know, are keen to stop advertisers making doubtful claims.

This simple plan is working out very well: all except one of the UK advertisers I have contacted so far have agreed to stop using the words ‘cure’ or ‘eliminate’ in their ads. The one which disagreed was passed to the ASA - and they agreed with us, and told them to stop it.

But a lot of ‘cure’ claims are being made in other countries and, with the increasing use of the web as an advertising medium, this can spill over into all other countries.

If you stutter, and the frustrations are immense, you might reasonably go to Google and enter ‘stutter cure’. You will then be greeted by a massive list of doubtful claims. Here are some examples:

- Loggita, who claim a 100% cure for stuttering in 25 days
- StammeringFree, who offer a stammer no more’ treatment, effective in 97% of cases
- JustBeWell, who will cure your stutter
- Stop Stuttering Secrets can cure you in three easy steps
- Stutter Cure, who, as you might imagine, will cure your stutter

This kind of slack and easy-going culture also affects the media, so that when they get served up a good story by the PR department of a stuttering ‘help’ organisation, they think they can talk about ‘miracles’ and ‘cures’ for stuttering, as everyone seems to do the same. And nobody stops them, because everyone is keen to sell their stuff, hype the outcome and give us a good happy story - and, hey, nobody does anything to say they shouldn’t. If you now put ‘stuttering cure’ or ‘stuttering miracle’ into YouTube, you’ll see what I mean.

Tuesday, October 28, 2008

What is coming up?

Not much is happening at the moment. Here are a few future events that should happen at some point. In genetics, Drayna's team is still working on tracking down genes in stuttering families and the stuttering population. I would expect results within the next year. In brain imaging, we should soon hear more from Ingham and Fox's team, and the groups in Oxford (Watkins) and in Paris. And the Finish group with new scanning technology. And others. And in treatment trial, Franken's group is comparing Lidcombe and an alternative, demand and capacity treatment. They have now 66 kids registered and are going to 100 or more I believe. But it will take more than a year before the first results I would guess. Then Ingham's group is also running a trial on their treatment for adults. And Onslow's group is running a study on kids before they start stuttering.

Sunday, October 26, 2008

Placebo or not?

Ora from New York City sent me an interesting article on the use of placebo by doctors: see here. The article explains that many doctors are using placebo (pills without any effect on the condition) to improve patients' well being by exploiting the placebo effect. The placebo effect is quite powerful. For example, let us take 900 patients with chronic headaches and divide them in three groups and give them either: nothing, a pill that does not contain an active compound, or Aspirin / Paracetamol. The winner is Aspirin / Paracetamol, but the second place is not shared but won by the placebo pill even though it contains no active compound. How is this possible? Here are possible explanations: you convince yourself that you feel better and override your body's feedback (it is a bit like putting your headphones on mute for 20 seconds when your girlfriend or parent launches into a tirade! :-), you feel better and more confident and your brain might release pain-killing neurotransmitters (putting yourself on drugs or natural painkillers), and so on. Placebo works better for some conditions than others.

An interesting challenge is the following: so if placebo works well, should doctors not use placebo, i.e. tell their patients that a pill works and then it works! Most alternative medicine is probably due to the placebo effect: you go to the practitioner, s/he talks to you, makes you feel better, and then gives you a placebo which he and you of course genuinely believe is working. And in the end it really helps. That's the paradox.

How about stuttering? There is a clear effect in the drug trials. I am convinced it plays a role in altered auditory feedback devices and conventional speech therapy. So does this mean that we should not use them? Someone could argue: Well they give more fluency, so who cares that it is placebo! My answer would be: yes short-term fluency gains but not long-term. And that's the key issue: placebo works well in the short-term.

Saturday, October 25, 2008

Not much happening

Not much has been happening over the last months that increased our understanding of the stuttering brain. As I mentioned before, scientists are hitting the complexity barrier with the new research avenues, namely brain imaging and genetics. The easy part has been done. It is one thing to put someone in a scanner and report functional or structural differences, but it is another to devise a experimental setup that can falsify or confirm a theory on stuttering. The same is true for genetics: we now know that genes are involved in stuttering in many cases, and we even have located the chromosomes in some cases. Even if we then know the genes, we again hit the complexity wall; it's like we know the killer but not who he (or she! :-) killed and why. In fact, very few scientists (and I am talking about the professional ones and not clinicians-turned-researchers) are well equipped to handle this situation. Many are trained to work well within the experimental paradigm (i.e. how to find the genes or how to scan and interpret the findings), but stuttering is a muddy territory where you need to fine-tune your methods appropriately to the idiosyncrasies of stuttering.

Tuesday, October 21, 2008

Lidcombe treatment of choice? ROUND II

And again on Lidcombe trials at Kuster's ISAD site on the question/answer page of Susan Block's article. Ann Packman, co-author of the Lidcombe trials, writes:
 Hi Sue, nice article. I would like to clear up some misconceptions that have been posted about the Lidcombe Program randomised control trial. The trial was reported by Jones et al. (2005) in the British Medical Journal. There was a significant treatment effect after 9 months, compared to the no-treatment control group. The study was conducted according to CONSORT guidelines (see http://www.consort-statement.org/ which specify the appropriate methods and analyses for reporting trials in medical journals. They have been in existence for over 15 years. The study is replicable, as is the Lidcombe Program. As for the 5-year follow up study (Jones et al. 2008) of the children in this trial, it is indeed the case that three of the children were found to be stuttering again, after at least two years of fluency. This tells us that: (1) For these children the initial improvement in stuttering was apparently due to the treatment, not natural recovery (2) These children were at least spared the social penalties of stuttering for some of the early school years (3) At time of discharge from treatment, SLPs need to advise parents to be vigilant in the long term and to contact a SLP and/or re-instate treatment at the first signs of the re-appearance of stuttering (4) Further research is needed to develop better ways of maintaining Lidcombe treatment effects. Without this long-term follow up study, we would not have this important new knowledge about the nature of stuttering and about the need to work to further improve Lidcombe outcomes. Ann
 Susan Block replies:
Hello Ann, thank you for this response. Your comments show exactly how attention to scientific principles facilitate the evidence base for our profession - but also how they can frustrate some people!
Does she actually refer to me or others who are trained scientists??? Anyway, I reply:
Most people are NOT frustrated by attention to scientific principles. I am frustrated about the poor application of scientific principles to therapy outcome research like conflict of interest (proving your own treatment), passive understanding and robot-like application of statistics, leaving out subtelties, and repeating of statements and deference to authority instead of engaging in counterarguments when challenged on the strength of evidence. I will show that EVERY single of Ann's sentences (to "clear up misconceptions" according to her words) are inaccuracte. (1) "the Lidcombe Program randomised control trial". Let's be clear which kind of RCT it is. It is not a double blind RCT, the highest standard, that allows to check whether it is the treatment itself that is sucessful. It is an open-label trial with the big disadvantage that even if the treatment arm shows a higher sucess rate you cannot say whether it was the placebo effect (the fact that the kids/parents had treatment), generic feature of ALL early intervention treatments (like parent-child interaction, easing parents' stress, adaptation to the treatment setting), or actually Lidcombe-specific feature. So you are NOT actually testing Lidcombe specifically but the whole package (placebo, generic and specific)! Moreover, the randomization was broken after 9 months and was not present in the long-term data. And let's note that 9 months is from the start of the treatment and NOT from the end of the treatment. Finally, the sample size was too low for randomization to equalise the two groups: as I discuss in my rapid response to Jones 2005 in BMJ. These arguments were confirmed and mentioned by Roger Ingham's group as he told me when I met him. So calling it a Lidcombe RCT looks very scientific but is a misnomen really! (2) "The trial was reported by Jones et al. (2005) in the British Medical Journal." It is irrelevant whether it appears in BMJ or anywhere else. It does not add to the debate, and only fallaciously implies "BMJ is a really good journal so the trial must be really sound". Moreover, you are not mentioning that I wrote a rapid response in BMJ criticising the statistics or if you think I as a PhD physics have no clue you could at least mention other critical feedback. (3) "There was a significant treatment effect after 9 months, compared to the no-treatment control group." As I said the stats are wrong. And again, 9 months after the start of the treatment, but not 9 months after the end of the treatment. I just re-read the article and you are writing that the kids are still in treatment! The relevant time period is starting at the end of treatment. ANY behavioural therapy will produce gains: diets, drug, giving up smoking. The important part is the relapse. (4) "The study was conducted according to CONSORT guidelines (see http://www.consort-statement.org/ which specify the appropriate methods and analyses for reporting trials in medical journals." First, these guidelines are for standard situations, but early intervention is very different because you have the natural recovery that distorts statistics and therefore you need many more kids to create truely balanced groups via randomization. You stopped at 47 kids rather then the 100 which would have improved the statistics dramatically. In fact, you had your design at 100. Why? Second, even if the guidelines are correct, it does not imply that the implementation of the guidelines was done correctly! Kids dropped out, you gave up the control group, you changed the sample size. (5) "They have been in existence for over 15 years." That is so symptomatic of bad thinking i.e. deference to some authority. I do not care how many years something is in existence. I only care about the strength of arguments. To show you how strange this is. I could argue: Well if it is 15 years old, it is too out-dated and should not be trusted! You might convince non-scientists but you cannot conduct a debate with such pseudo arguments. (6) "As for the 5-year follow up study (Jones et al. 2008) of the children in this trial, it is indeed the case that three of the children were found to be stuttering again, after at least two years of fluency.". Again this sounds very respectable, but I have actually read the article (unlike most therapists). It is a desaster. The MAJORITY of the kids could not be contacted anymore. Why? Or did someone not contact them because they stuttered? Moreover, 3 kids relapsed is 86% recovery rate, and considering the small sample you cannot even be sure you beat the natural recovery. OK you argue that the natural recovery is much lower, but please show it to me in the control group or achieve 90% in a sample of 100 kids! "Without this long-term follow up study, we would not have this important new knowledge about the nature of stuttering and about the need to work to further improve Lidcombe outcomes. " Again, this sounds really great but your study was so poorly implemented how can we trust your results. From 134 kids referred to treatment and 47 completing it, you are left with 28 kids! So where is this important new knowledge? How can you have new knowledge on such a poor sample? The need to further improve Lidcombe? Sounds like from a spinning doctor. THE TRIAL IS NOT SET UP TO PROVE LIDCOMBE IS EFFECTIVE, so how can you say you will improve it? (7) "This tells us that:" "1. For these children the initial improvement in stuttering was apparently due to the treatment, not natural recovery (2)" NO AGAIN THE TRIAL DOES NOT EXCLUDE PLACEBO OR NON-LIDCOMBE EFFECTS. Moreover, you could even argue that those you would have recovered anyway just recovered faster in the 9 months because they have the inherent ability anyway. And we know from adult therapy, that nearly everything works for some time. Not speak about getting used to clinic environment. To summarise, I am just fed up with sloppy pseudo-scientific replies that 99% of the clinicians and stuttering community swallow happily because no-one actually sits down and looks at the trial carefully. Or she or he would find that it is a can of worms. But let me conclude by saying that at least you try to do evidence-based research. So the fact that I can criticise your research is progress in itself for I cannot criticise other approaches because they do not do any outcome research.

Monday, October 20, 2008

Hollins program

StutterTalk.com did an interview with Webster from the Hollins institute. A very large private clinic for the treatment of stuttering and they have the domain name stuttering.org! I have never looked at them very closely. I will listen to the interview and report back. Make up your own mind here.

Self-report on Abilify

A reader has sent me his self-report on the first four weeks on Abilify. I hear Abilify mentioned often. For example, Ludo Max told me that they had some very positive experience with Abilify, but they never got the money for more research, I believe. Again, we need to be careful to its real efficacy. Here is the 4-week report:

It has been 4 weeks now since I started taking Abilify and so far so good.I am 28 years old and have stuttered all my life. This is the first time I am taking medication for my stutter. I started initially on 2 mg and increased to 5 mg after 2 weeks.All secondaries like eye blinking and face contortions have gone and I feel myself a lot more in control of my speech. For the first time in my life, I have started to make eye contacts while talking.I have gone from a severe stutterer just a one month back to a mild one now.
I have started to talk a lot more at work and with my friends and family. I am not expereincing that much rush of blood and anxiety before talking.
Abilify is not a cure and I still have blocks and I still stutter. But the blocks frequency and duration have reduced substantially and I seem to apply easy onset techniques to get out of blocks more easily and frequently now than before.
I haven't had any adverse side effects so far. I haven't gained any weight, though I have been also watching my diet and working out and also I haven't experienced dizziness or restlessness. I hope that the positive effects of Abilify on my speech don't wear off after some time.

Thursday, October 16, 2008

The tell-signs of flawed research

Back to John Ioannidis's work (see my post) and his tell-signs of flawed research. Let's see how much is true in stuttering research.

Corollary 1: The smaller the studies conducted in a scientific field, the less likely the research findings are to be true.

Absolutely, most samples are less than 30. He recommends 1000s!

Corollary 2: The smaller the effect sizes in a scientific field, the less likely the research findings are to be true.

Most research does not include the effect size, but only look at statistically significant differences. If they did, they would find small effect sizes.

Corollary 3: The greater the number and the lesser the selection of tested relationships in a scientific field, the less likely the research findings are to be true.

Yes, most studies look at many different variables making it more likely that some correlate by chance.

Corollary 4: The greater the flexibility in designs, definitions, outcomes, and analytical modes in a scientific field, the less likely the research findings are to be true.

Stuttering is very difficult to quantify unlike weight for example. It is a moving target, because people who stutter can fluctuate dramatically. Compare this to a weight measurement where the difference in weight between morning and evening is probably just a kg or so.

Corollary 5: The greater the financial and other interests and prejudices in a scientific field, the less likely the research findings are to be true.

There are great financial incentives for stuttering medication: a potential market worth 100s of million dollars. There are financial incentives in AAF (altered auditory feedback) devices, for example SpeakEasy devices. They are pushing very hard on spinning the evidence. Just have a look at their website. Regarding conventional treatments including Lidcombe, there is some money to be made but the sums involved are peanuts in comparison. It is more a matter of justifying their existence as researchers and clinicians (giving their life a meaning and purpose) than about pure financial gains.

There are certainly prejudices. This is especially true for the clinicians who test their own treatment, or you try to validate their long-held beliefs. Compare this to a geneticist who studies the genetics of stuttering (he has no prejudice on what he wants to confirm). He has no hypothesis.

Corollary 6: The hotter a scientific field (with more scientific teams involved), the less likely the research findings are to be true.

The two hot areas I see are: Lidcombe treatment and emotionality/sensitivity studies... This is very different to the hot area of brain imaging or genetics where it is hot to do research but no-one knows what should be found!

Sunday, October 12, 2008

If you want to do a post-doc in stuttering

Ludo Max is looking for a post-doc: check here:
The Laboratory for Speech Physiology and Motor Control in the Department of Communication Sciences at the University of Connecticut (Project P.I.: Ludo Max, Ph.D.) is seeking applications for a postdoctoral position to study various aspects of the neural systems underlying sensorimotor control of speech movements in individuals who stutter. This NIH-funded project involves both psychophysical and neuroimaging (fMRI) experiments, and the selected candidate will have opportunities to contribute to both lines of work. Facilities in the lab include, among other things, electromagnetic motion tracking for speech articulatory movements as well as for upper limb movements, real-time digital signal processors for auditory perturbations of speech and a Phantom 1.0 robot for mechanical perturbations of the jaw, tendon/muscle vibration, EEG/EP systems, and a virtual display environment for arm motor learning studies.

Candidates with a Ph.D. degree in cognitive/behavioral neuroscience, motor control, biomedical engineering, speech and hearing science, experimental psychology, and related fields are encouraged to apply. Good programming skills (Matlab and C++) are preferred. Candidates should be highly motivated and have an interest in publishing research in the area of speech motor control and stuttering.

I am sceptical he will find someone who can code well in Matlab and C, and at the same time knows something about stuttering. On the other hand, if the post-doc does not know anything about stuttering, he or she will be less biased and Ludo has the expertise anyway.

Another flawed Lidcombe study

And yet another flawed study on Lidcombe. This is especially disappointing because the group is independent of the Australian group around Mark Onslow. The co-author is Barry Guitar, university professor and the author of a well-known (and in general well written) text book on stuttering called
Stuttering: An Integrated Approach to Its Nature and Treatment . However, his research and his presentations on temperament and stuttering are suspicious to me. He might be a good clinician but a not very good science mind unfortunately. I would guess the first author is an enthusiastic and bright graduate student who has effectively wasted her or his time with research that has little relevance.

 Am J Speech Lang Pathol. 2008 Oct 9.

Long-Term Outcome of the Lidcombe Program for Early Stuttering Intervention.

University of Vermont.
PURPOSE: To report long-term outcomes of the first 15 preschool children treated with the Lidcombe Program by speech-language pathologists (SLPs) who were inexperienced with the program and independent of the program developers. Research questions were: Would the treatment have a similar outcome with inexperienced SLPs compared to outcomes when implemented by the developers? Is treatment duration associated with pre-treatment measures? Is long-term treatment outcome affected by variables associated with natural recovery? METHOD: Fifteen preschool children who completed the Lidcombe Program were assessed prior to treatment and at least 12 months following treatment. Pre-treatment data were obtained from archived files; follow-up data were obtained from interviews and recordings completed after the study had been planned. RESULTS: Measures of stuttering indicated significant changes from pre-treatment to follow-up in percent syllables stuttered (%SS) and Stuttering Severity Instrument-3 (SSI-3) scores. Pre-treatment severity was significantly correlated with treatment time. Handedness was the only client characteristic that appeared to be related long-term treatment outcome. CONCLUSIONS: The treatment produced significant long-term changes in children's speech, even when administered by SLPs newly-trained in the Lidcombe Program. Treatment results appear to be influenced by pre-treatment stuttering severity.

Without having read the article itself, I can see several flaws:

1) A sample size of 15 is much too small. Either you do at least 100 or you do not do it at all! The number is especially high because of the natural recovery rate increasing statistical fluctuations.

2) They have not controlled for natural recovery rate. It makes the results appear much more positive that they really are, because some will recover within one year naturally anyway and the stuttering severity will automatically go down. Here is a simple example. I have 20 kids. Let's assume 10 would have recovered within one year without treatment. Before, they all stutter at 5%. After one year without treatment, only 10 stutter, and the average stuttering rate is 2.5% (10 kids at 0 and 10 kids at 5%).

3) They try to find correlations in data with a very small sample size. Their finding on handedness is most likely a fluke.

But interestingly, the abstract seems to suggest that some kids are still dysfluent (I would have to read the article which costs money to access). The existence of dysfluent kids is not affected by statistics. So we can say that Lidcombe is not the cure it was claimed. In fact, I heard from many other therapists that some kids do not become fluent.

Thursday, October 09, 2008

Why Most Published Research Findings Are False

John Ioannidis is saying exactly in this article what I have always believed that most published medical research is wrong. Stuttering is no except to the rule.
There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.
He should write a second article on what happens when others are pointing out issues in research. I tell you what happens when I point out issues: nothing, absolutely nothing. It is still being spread, and the only antitode is to shout as loud as possible: it's false. And of course I need to face up that people start to think of me as an eccentric outside who are no clue, really.

Monday, October 06, 2008

Correction on Indevus share price jump

I just realised that my post is probably not telling the whole story about Indevus' share price jump, because on the same day, they released information on another compound which this article by Anuradha Ramanathan claims has provoked the jump:

Shares of Indevus Pharmaceuticals more than doubled after the company reached a deal with U.S. health regulators to use its existing data for an early re-application seeking marketing approval for its testosterone replacement drug.

The agreement with the U.S. Food and Drug Administration removes the need for more studies and Indevus now plans to apply again for marketing approval in the first quarter of 2009, and launch the drug in the fourth quarter, the company said in a statement.

Saturday, October 04, 2008

Half brain

I just saw a documentary on people who only have one half of their cortex (the high-level brain). When they spoke in front of the camera, they seem to have markable disfluencies. They did not stutter but they looked a bit like "recovered" stutterer who control themselves not to stutter but you perceive their mini-block: instead of getting out of control, they just move to the next word after a slight hesitation. Not sure whether it has a connection to stuttering.

Friday, October 03, 2008

Indevus shares jump by 50%

The shares of Indevus, the licence owner of Pagoclone, jumped by 50% in light of the announcement of a new partner Teva and the Phase IIb trial. The graph is from Yahoo!Finance.  It is a good example that you need to know both timing and impact of information to make money. I knew that the stock would jump upon such an announcement, but it did not know the timing or whether it would happen. Actually, I am an idiot. Come to think about it, I kind of knew, because in June I was told by reliable sources that there was a meeting for a new trial and that they would go ahead. I should have bought the stock and made a killing. Oh well...

Think about it, 50% higher means that the company is worth double from one day to the other. Why? Because investors believe that the future cashflows of the company are twice as high (neglecting discounting)! And it is twice as high, because 2-3 people at Teva think it is a risk worth taking. How much do they know about stuttering? Probably, very little. And I am sure they are not aware of many methodological pitfalls. But, the market trusts their judgement for the moment and so the value of Indevus goes up by 50%. I think the chances of clear success are moderate, but I also have not see the individual responsiveness of each patient.

Now everyone at Indevus who gets paid in shares for bonuses is worth twice the amount! Everyone will do everything to get Pagoclone approved. It could make or break for them as millionaires! Just imagine the other pharmaceutical companies looking at Indevus. Surely they will brainstorm on how to jump the band waggon. If any of you are such a company, you can hire me as a consultant! ;-)
Here is an Associated Press article, and here an extract:
Shares of Indevus Pharmaceuticals Inc. more than doubled Friday after the company said it is collaborating with Teva Pharmaceutical Industries Ltd. to develop a treatment for stuttering and could move forward with its delayed horomonal disorder drug.
Indevus' stock surged $1.78, more than doubling to close at $3.51. The Lexington, Mass.-based company's stock has traded between $1.19 and $8.22 over the past 52 weeks. Shares of Israel-based Teva, which makes both generic and branded drugs, rose 31 cents to $46.03.

Thursday, October 02, 2008

100'000 visitors!!!!!!!!!!

I completely missed the 100'000 visitor celebration! Also the average number of visitors per day is 230! I have roughly 1000 unique visitors per week from all around the world; most are from the US.

Lidcombe treatment of choice?

Susan Block replied to my comments on her statement that "Lidcombe should be the treatment of choice" (see her ISAD article here):
I think we have discussed some of your comments before. It is the case, in my opinion that it has the best evidence to date for preschool children. The Franken et al study was almost impossible to replicate as their comparative treatment was not well defined. I think it is the case in the Jones et al study that the children in the Lidcombe treatment group made so much positive change that they could not justify maintaining children in a control group.

And I replied:
It is reasonable for you to say "in my opinion that it has the best evidence to date for preschool children". However. First, you actually wrote "should be the treatment of choice" implying a moral imperative i.e. it would be irresponsible for therapists not to use Lidcombe? Is it? Second, I repeat again that the trial described in Jones et al 2005 has a follow-up study Jones et al 2007 which you do not cite but in my opinion should. As I am sure you teach to your students, a treatment should be evaluated based on long-term outcome data and not short-term sucess. And the Jones et al 2007 paints a much more sober picture (apart from methodological issues). Have you read it? Regarding your comment "The Franken et al study was almost impossible to replicate as their comparitatve tretment was not well defined.", it is not relevant whether the trial is replicable or not for it to be true or not. In fact assuming the comparative treatment was completely ill-defined and chaotic, it managed to do as well as Lidcombe. This actually supports the alternative view that any treatment will be succesful. In any case, a new trial with a larger sample and extra care of defining the comparative treatment is under way. Regarding replicability, the same is true for the Lidcombe trial, because as you yourself say "it is the case in the Jones et al study that the children in the Lidcombe treatment group made so much positive change that they could not justify maintaining children in a control group.". We can never repeat it again with a control group! Would you therefore argue that it is not valid?

Wednesday, October 01, 2008

ISAD 2008

Check out Judith Kuster's online conference. With many good quality and no quality discussions on stuttering, research and treatment.

I have already posted a comment to Susan Block's article What clinicians should know to avoid the spreading of that myth Lidcombe should be used:
You are writing that "Current research indicates that the Lidcombe Program should be the treatment of choice for young children who stutter (Jones et al, 2005; Lincoln & Onslow, 1997)." This is misleading 1) It implies that Lidcombe is better than other early interventions. However, Lidcombe has never been tested against other forms of early intervention in a random control trial. It could well be that ANY intervention has a similar (or no) effect. There was only one pilot trial by Francken in the Netherlands and there was no difference with demands and capacity. She is currently conducting a large scale study between Lidcombe and DC. 2) You only cite the Jones 2005 article, but there is a follow-up paper from this year with long-term outcome. Three children have relapsed and many kids were not contactable any more. The sample is close to the natural recovery rate, not to speak 3. The study of Jones 2005 is questionable and has statistical and methodological flaws: wrong statistics, no long-term control group, and more. I think clinicians should know these facts. Evidence based practise is important but should be based on WELL ESTABLISHED evidence.

Tuesday, September 30, 2008

A revolution is happening.

A revolution is happening. It is the first time in the history of stuttering research that millions are being spent to test and develop a treatment for stuttering. Don't be mistaken. The stakes are dramatically increased. And do not expect some pseudo-science happening with waffling professors from the fiefdoms with no reality checks. The industry does not invest millions lightly, they know that they face reality checks, reality will hit them and they will do anything to get this working. And expect anything to include massive spinning of results in case the positive effects are there but very modest. And expect other pharmaceutical companies to at the very least do intensive brain storming to prevent them from getting a monopoly on a potential new market. We are entering the big bucks area of stuttering treatment.

I hope for the best (an effective treatment to reduce stuttering), but expect the worst (moderate efficacy in some with massive efforts of the companies to still make money but as a side effect a better understanding of stuttering).

Disclaimer to US readers: TheStutteringBrain blog specifically denies any responsibility for the wardrobe malfunction of the revolutionary Marie in the heat of the battle!

The pharmaceuticals are not sure themselves

And now the cold spin. Finally, Indevus managed to get an investor Teva in who will foot the bill for further clinical trials and thereby bets on Pagoclone being effective. Why did it take so long?
Indevus previously announced promising data from its 8-week, placebo controlled, double-blind, multi-center Phase II trial in patients with persistent stuttering which showed that pagoclone produced a statistically significant benefit in multiple primary and secondary stuttering endpoints compared to placebo. 
The text is a bit misleading in my view as it looks as if it is a significant effect. Don't confuse statistically significant with significant! Statistically significant means that with a high probability there is a difference in effect between the group that took Pagoclone and those who received a placebo. However, it does not say anything about how large this effect is! In fact, as I mentioned before. The reduction of stuttering in comparison to placebo was only about 10% in week 8. On the other hand, you can argue that you don't care about this fact, and only look at the absolute effect because it is the relevant measure for a person who stutters. However, it does show that the compound itself does not seem to be very effective at all! The open label phase (where everyone could choose to take the compound) was more successful. It is also possible that only a subgroup responds positively to Pagoclone and the other not at all, so the mean effect is not a good measure and does not show the large improvement on a sub group! Finally, it has not been published in a journal yet, as far as I know.
Under the terms of the Agreement, which is subject to applicable regulatory clearances and customary conditions, Indevus will conduct and Teva will reimburse Indevus for its expenses for a Phase IIb study. The placebo-controlled study will involve approximately 300 patients with stuttering in the U.S. treated for a period of six months and is expected to commence enrollment by Q1 2009.
I am also not exactly clear on what a Phase IIb study is. Wikipedia says: "Phase II trials are performed on larger groups (20-300) and are designed to assess how well the drug works, as well as to continue Phase I safety assessments in a larger group of volunteers and patients. Phase II studies are sometimes divided into Phase IIA and Phase IIB. Phase IIA is specifically designed to assess dosing requirements (how much drug should be given), whereas Phase IIB is specifically designed to study efficacy (how well the drug works at the prescribed dose(s))." I have the suspicion that in this case Phase IIb simply means "let's do it again to be sure before doing Phase III but let's do it a bit larger, longer and fine-tune", see above.

The main difference to the last Phase II trial is probably three-fold. First, 300 instead of 132 people will participate so the statistical error will be lower. Second, they will fine-tune their methodology from the last trial. Third, they observe them for 6 months. The open label was more successful, and they probably want to collect placebo-controlled data to confirm their suspicion that the full effect comes out over several months.

But the real reason might well be, because Tera and Indevus are not 100% convinced about the efficacy of Pagoclone. Stuttering is a very tricky disorder, and they might even have read my blog! ;-) So they probably want to play it safe, and re-do the last trial but with a bigger sample size and fine-tuned methodology. And the calculation is simple: if you do a real Phase III with 1000s of people, the costs are a multiple of the 300, and probably too high a risk. Wikipedia writes on Phase III: "Phase III studies are randomized controlled multicenter trials on large patient groups (300–3,000 or more depending upon the disease/medical condition studied) and are aimed at being the definitive assessment of how effective the drug is, in comparison with current 'gold standard' treatment. Because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run, especially in therapies for chronic medical conditions." I may add that medication can get approved after a successful Phase IIb and Phase III runs while the medication is already on the market.
We are excited that we have partnered pagoclone with a leading pharmaceutical company with a focus on central nervous system conditions,"said Glenn L. Cooper, M.D., chief executive officer and chairman of Indevus."There are currently no approved drugs anywhere in the world for patients with stuttering. Pagoclone has tremendous potential to become a highly significant commercial product, as well as to provide a ground-breaking therapy to then early three million Americans and millions of patients around the world who are afflicted with this condition. The deal we have negotiated with Teva allows us to conduct a definitive Phase IIb trial, funded by our partner. If the trial is positive, we believe that both companies will have a unique opportunity to commercialize the first pharmaceutical product for the millions of patients who stutter.
Typical CEO-bla bla bla! He doesn't really say anything, but it sounds good! For example, "tremendous potential" but of course potential might not translate into a real medication. So it is safe to say it anyway!

Watch the phrase "to conduct a definitive Phase IIb trial". Why use "definitive"? I think it is a slip of the hand, which reveals the mood they are in: They are not really sure themselves about the "tremendous potential" but this second trial will definitively give us a clear result. And any way Teva is footing the bill. And if it works fine, we just take 50% of the profits which is still millions.

Saturday, September 27, 2008

Breaking News: Pagoclone is going to Phase IIb

LEXINGTON, Mass., Sept. 26 /PRNewswire/ -- Indevus Pharmaceuticals, Inc.(Nasdaq: IDEV) today announced that it has signed a development, license and commercialization agreement with Teva Pharmaceutical Industries Ltd. for the exclusive, worldwide rights to pagoclone. Indevus previously announced promising data from its 8-week, placebo controlled, double-blind, multi-center Phase II trial in patients with persistent stuttering which showed that pagoclone produced a statistically significant benefit in multiple primary and secondary stuttering endpoints compared to placebo. Pagoclone is a novel member of the cyclopyrrolone class of compounds and acts as a gamma aminobutyric acid (GABA) selective receptor modulator.

Under the terms of the Agreement, which is subject to applicable regulatory clearances and customary conditions, Indevus will conduct and Teva will reimburse Indevus for its expenses for a Phase IIb study. The placebo-controlled study will involve approximately 300 patients with stuttering in the U.S. treated for a period of six months and is expected to commence enrollment by Q1 2009.

Following the completion of a successful Phase IIb study, the Agreement provides for Indevus to participate on a 50/50 basis with Teva in the U.S.,sharing development and marketing costs, and splitting future profits, in addition to receiving milestone payments. Under certain circumstances, either party may convert the Agreement from the 50/50 arrangement to a royalty structure where Teva will be responsible for all development and commercial costs in the U.S. and Indevus would receive royalties on net sales, in addition to milestones. In either case, if the arrangement continues, Teva will be responsible for the conduct of the Phase III program.

For territories outside of the U.S., Teva will be responsible for all future development and commercialization and Indevus will receive milestones and royalties on net sales.

Under the 50/50 participation, Indevus could receive up to $92.5 million(including the Phase IIb study expenses) in U.S. and European development milestones and R&D reimbursement. In the event of a conversion to the royalty structure, in addition to the $92.5 million of milestones and reimbursements,Indevus could receive up to $50.0 million in U.S. based sales threshold milestones.

We are excited that we have partnered pagoclone with a leading pharmaceutical company with a focus on central nervous system conditions,"said Glenn L. Cooper, M.D., chief executive officer and chairman of Indevus."There are currently no approved drugs anywhere in the world for patients with stuttering. Pagoclone has tremendous potential to become a highly significant commercial product, as well as to provide a ground-breaking therapy to then early three million Americans and millions of patients around the world who are afflicted with this condition. The deal we have negotiated with Teva allows us to conduct a definitive Phase IIb trial, funded by our partner. If the trial is positive, we believe that both companies will have a unique opportunity to commercialize the first pharmaceutical product for the millions of patients who stutter.
(Thanks to Holger!)

Can you help Connecticut scientists?

Ludo Max is looking for children and adults who stutter: see here. When I visited him last autumn, I also participated in one experiment, and I can confirm that I survived!
If you stutter or if your child stutters, you can make an important and valuable contribution to the scientific understanding of stuttering.

Researchers in the Laboratory for Speech Physiology and Motor Control in the Department of Communication Sciences at the University of Connecticut are conducting several studies that may result in new scientific knowledge about the problems involved in stuttering. Participating in any of these projects provides a wonderful opportunity to make a contribution that may benefit all individuals who stutter.

We are currently recruiting children to participate in our studies in Storrs (CT) and adults to participate in our studies in Storrs or New Haven (CT). All participants receive financial compensation and free speech, language, and hearing testing. Children also receive a small book or toy.

Children between the ages of 3 and 9, if eligible, will be invited to complete tasks such as speaking into a microphone while wearing earphones, listening to tones while wearing a cap with sensors that record the brain's responses to those tones (see top picture on the left), or pointing to visual targets with a small movement sensor taped to the finger (see middle picture on the left).
Adults between the ages of 18 and 50, if eligible, will be invited to complete tasks such as speaking into a microphone while wearing earphones, speaking with small movement sensors attached to the lips, jaw, and tongue (see bottom picture on the left), or speaking while lying in an fMRI scanner at Haskins Laboratories/Yale University.

If you want more information about any of these studies, or if you want to find out if you or your child are eligible to participate, please contact Dr. Ludo Max by e-mail (ludo.max@uconn.edu) or telephone (860-486-2630). Thank you in advance for your consideration.

Friday, September 26, 2008

Toronto and Does your child stutter?

If your child stutters (or not!) and you can make it to Toronto, please consider taking part in this research project. It is important for us to increase our understanding of stuttering, and hopefully one day your child and everyone else can profit from improved treatments resulting from such research!

Does your child stutter? The University of Toronto Speech Fluency Laboratory needs both children who stutter and children who do not stutter to participate in a research project. If your child qualifies for the study you will receive a speech, language and hearing assessment. You will be compensated for your time.

Please email d.beal@utoronto.ca if you have a child who is:

1. Between the ages of 7 and 12 years old
2. Right handed

Benefits of the study include:

1. A speech, language and hearing screening for your child
2. A free 100 page booklet on stuttering
3. Compensation for your participation and travel
4. Help advance our knowledge of the brain and the role it plays in hearing, speech and stuttering!

Tuesday, September 23, 2008

Back from holiday

Two major events happening in my holidays.

First, the meltdown on the investment banks. WOW! The Masters of the Universe are gone just like that. Bear Stearns (for which I worked as a risk manager, see a previous post) gone, Lehman Brothers gone, Merrill Lynch bought up, and Morgan Stanley and Goldman Sachs becoming commercial banks. They all need liquidity to work, and they could not get sufficient liquidity anymore. It will change Wall Street and finance forever, after all they were the drivers of most innovations and hired the brightest, most focused, hard-working people around.
Second, the message is going around that bilingualism is a risk factor in non-recovery of stuttering based on research done by Prof. Howell's team at University College London. The Welcome Trust has financed the research and is pushing the message: see here. Here is the summary:
Bilingual children who learn two languages in early childhood are more likely to develop stuttering than those who speak another language in the home and do not learn English until they attend school, according to research funded by the Wellcome Trust.
I will have a closer look and tell you my impression. Two immediate thoughts: bilingualism means more work for the brain but would it affect stuttering, and the sub-sample of bilingual kids is too small and induces large statistical uncertainty. But I need to read the article and do the statistical calculations.

Sunday, September 07, 2008

The StutteringBrain is on holiday

I am on holiday until September 19th, but might moderate comments from time to time. Till then....

Wednesday, September 03, 2008

AAF not effective?

Here is a study that claims that there is no clear fluency gains when using altered auditory feedback in a real environment:

1: J Speech Lang Hear Res. 2008 Aug 11.

Effects of the SpeechEasy on objective and perceived aspects of stuttering: a six-month, Phase I clinical trial in naturalistic environments.

University of Colorado at Boulder.

PURPOSE: Effects of the SpeechEasy when used under extra-clinical conditions over several months were investigated. Primary purposes were to help establish Phase I level information about the therapeutic utility of the SpeechEasy and compare those results to previous findings obtained in laboratory and clinical settings. 

METHOD: Eleven adults who stutter participated. A nonrandomized, ABA group design was utilized. Speech samples were collected every two weeks in extra-clinical environments. Qualitative data was collected through weekly written logs and an exit questionnaire.

 RESULTS: Group analyses revealed a statistically significant effect of the SpeechEasy immediately post-fitting, but no treatment effect across four months' time. Individual responses varied greatly with regard to stuttering frequency and subjective impressions. Relatively more stuttering reduction occurred during oral reading than formulated speech. 

CONCLUSIONS: Based on this protocol, Phase II trials are not indicated. However, positive individual responses and self-reports suggest some clinical utility for the SpeechEasy. The use of more challenging sampling procedures strengthened external validity and captured more modest altered auditory feedback effects compared to those previously reported in laboratory settings. Device use coincided more so with positive subjective impressions than measurable fluency improvement, highlighting challenges facing clinicians when implementing principles of evidence-based practice, including client-based preferences.

Tuesday, September 02, 2008

My interview on StutterTalk

You can listen an interview with me on StutterTalk.

Here is a summary: (from what I remember, which is probably very biased!)

We started out having a speech goal. Mine was to speak slowly with pauses, and I was able to maintain this for about 3 seconds. 

Crackpot Award:
I explain that I want to break the code of silence and consensus by naming and shaming the most extreme offenders in ignoring scientific evidence and promising cures. I read out loud an email, where I show how crackpots are unable to engage in a constructive debate on stuttering. Greg agrees with me that no matter how nice you are or how hard you worked if your idea is wrong it is wrong and you need to be told loudly and clearly and why it is wrong. 

Measurement of sucess:
Peter complains about the excessiveness of measuring treatment sucess. I agree with him. It is like telling someone that your new car costs 17'4563 dollar and 34 cents. For all practical purposes, the car costs 17'500 dollars. There is no need for great accuracy. The false accuracy fallacy is a warning sign for pseudo-science at work. For therapy work, rough qualitative assessment by the therapist and patient is fine for me. What would you do with all this information anyway? Of course, if you want to evaluate a treatment method, you need to do it thoroughly. So my stance is: Either do it very big and very well, or don't do it at all. Greg came in with the needs for standards, and I said that the health services like to see such standard as they now need to set targets.

Lidcombe & early intervention:
I say that I am not against the treatment method per se but the way it is marketed promising a lot and based on weak and flawed research. In fact, I have no issue send my kids there. However, they have not showed long-term efficacy as they claimed. And most importantly, they have not shown that Lidcombe is better than any other treatments, because it has not been tested against others. Greg made a blatantly obvious observation that totally escaped my mind so far: They (different approaches) all talk about theory, but when you actually look at what they do, it is very similar! They all talk to parents, the kids know that it is about their speech, do speech exercises, and so on. I mention that Marie-Christen Franken from the Netherlands is currently running a trial where she compares Lidcombe with demands and capacity theory. 

I say that medication is the only hope for improvement of ALL people who stutter on a large scale, because behavioural therapy might work for some but not for all. In the same way as diets work for few, because most are not able to stick to the new behaviours. Peter is unhappy, and explains that for two years he consistently worked on changing his behaviour. I reply with: Good on you, but many including myself were, are or will not be able to do what you have done. We are not Peters! Peter felt embarassed and somehow emotionally cannot handle the fact that he is special in this respect. I also emphasised that I am not saying that there is such medication now, or that there even will be such a medication, and that it will be a cure. My prognosis is rather than there will be better (and possibly individualised) medication within 10 years in combination with behavioural therapy that makes stuttering more or less manageable for all. It is a guess, no more. I am not fond of medication pe se also due to side-effects, but I do not see another efficient way forward unless we get some very efficient behavioural therapy.

I said that I am waiting for old professor with old ideas to retire. In physics, we say that progress is not made by old professors changing their old ideas but by them dying out!