Paper accepted explaining why clinical trials o... - Thyroid UK

Thyroid UK

137,788 members161,605 posts

Paper accepted explaining why clinical trials on T4/T3 combination disagree with physiological findings about relation of thyroid and body

diogenes profile image
diogenesRemembering
28 Replies

This paper will soon appear in Journal of Thyroid Research, It's extremely important as it asks the question as to why basic physiological discoveries about how the thyroid and body interact are not mirrored equivalently by clinical trial results, that do not consistently support combo therapy over mono therapy with T4. Put simply, ALL randomized clinical trials attempting to answer this question are faultily based, and by their basic error in statistical analysis and inadequate power of numbers of patients, cannot address the questions they are asking. We go into great detail as to how this should be so and suggest remedies for better trial design in the future. The irony is that NICE are at present drawing up guidelines based on the very completely flawed "evidence" from trials. Obviously it follows their conclusions are fatally flawed and no weight can be given to the outcome if it is based on such work. It should not take too long for this paper in J Thyroid Research (an open journal) to be published and when this happens, it should be addressed to the NICE deliberators to give them pause for thought. The title is:

"Lessons from Randomised Clinical Trials for Triiodothyronine Treatment of Hypothyroidism: Have They Achieved Their Objectives?"

It will quite a blow for the thyroid establishment to find they have wasted their time and come to wrong conclusions as a result.

Written by
diogenes profile image
diogenes
Remembering
To view profiles and participate in discussions please or .
Read more about...
28 Replies
Jumbelina profile image
Jumbelina

Thank you for this and for all you do diogenes

lady_eve profile image
lady_eve

I look forward to reading this, if possible. It sounds very important.

And the big question is will these people admit they were wrong? I think not! Thanks, diogenes. I always learn from and enjoy your research. irina

diogenes profile image
diogenesRemembering in reply to

This time they will have to copy Trumpism, saying "t'aint so" with their brains, eyes and ears tight shut. But the killer is that no longer can they confidently state "what is so" with an conviction.

in reply to diogenes

Maybe they can coin a new term (taking a page from Pres T's playbook): "Fake medical research!" LOL-but not really.

Angel_of_the_North profile image
Angel_of_the_North in reply to diogenes

Are you sure? "They" have just ignored decent research on saturated fat and gone with the flawed research so they wouldn't have to be proved wrong.

diogenes profile image
diogenesRemembering in reply to Angel_of_the_North

There will never be a "mea culpa" moment by the medical profession. That isn't how it works. When the evidence is overwhelming, they quietly change track without reference to the bad ideas held before. It's like a pinprick in a balloon. At first very gradually, the balloon imperceptibly loses its size. Then the hole gets bigger, the balloon shrinks faster and at last bang, its gone. No wrong idea is for ever - it just takes time for it to die.

Hillwoman profile image
Hillwoman in reply to diogenes

True, but it's a pity that bad ideas take longer to die than people do.

greygoose profile image
greygoose

Really like the sound of that! :D

linda96 profile image
linda96

I’m looking forward to reading this paper.. it can’t be published soon enough.

NICE have handed the Job of compiling the Thyroid Guideline to the National Guideline Centre, who in turn asked (?) the Royal College of Physicians. I’m not sure how all this is interconnected or who asked who. You would have to make further enquiries to make sure this information is correct.

jgelliss profile image
jgelliss

Diogenes

Grateful to have you in my thyroid journey . It's Wonderful Kind Caring people as yourself that give us hope with our thyroid journey .

dolphin5 profile image
dolphin5

Brilliant!! Thank you!!!

Musicmonkey profile image
Musicmonkey

Thanks again for all you do for us diogenes

Katepots profile image
Katepots

How fabulous! Is this paper going to be given to Lord Hunt at the meeting? Would be a great ace up the sleeve to produce when the BTA and BTF representatives may be being a little unhelpful.

A lot of papers I've read on thyroid disease are woefully inadequate. As you say, too small sample size, etc., oh and statistical anomalies. Many raise too many questions than give answers. A lot of their "research" appears flawed by too many variables being present in their analyses to be able to get any sort of conclusion. Unless one seeks a "conclusion" with bias. Very amateur work compared to other fields of science and engineering. Looking forward to reading your paper. If I hadn't suffered Hashimoto's disease I would never have found out just how bad some "academics" are in the thyroid world!!

SilverAvocado profile image
SilverAvocado in reply to

Possibly because a lot of medical research is done by medics, who are practitioners rather than scientists, so they have no research training. I'm a social scientist, and years ago I used to give a single lecture on statistics to doctors planning their first clinical trial, and that was all they got. The same kind of material our own students had as first years.

I worked in education for years and there's the same problem, the field is full of teachers rather than researchers, so research practice isn't valued.

in reply to SilverAvocado

Yeah I think you've hit the nail on the head there. I can imagine the maths and statistics taught is rather meek and mild, and not too in depth. Assuming they stayed for the full half hour! Joking aside, medical students/practitioners have a lot of other things to cover. Shame really though, as a lot of medical research papers tend to exhibit some form of statistical analysis and many are lacking in quality. So are you saying your own social science students were much more equipped to analyse data using statistical methods than the medical students?

SilverAvocado profile image
SilverAvocado in reply to

Yes, I'd say the social science students were more equipped, they'd have studied statistical methods for 10-15% of their time all the way through, including a lot on research design and questions. I think one of the biggest issues with tacked on statistics is not having an understanding of the kind of question that can be addressed.

And to clarify, I am very very far away from a statistical methods specialist, in fact I am primarily a social theorist, which is more or less philosophy! This was the absolute basics, and very new ideas for most of them :(

diogenes profile image
diogenesRemembering in reply to SilverAvocado

From the paper I deposited with Louise Roberts the other day, a little excerpt:

That is, even in the best-case scenario, we

should not think of a correlation in group data as an estimate that generalizes to any given individual in the population. Stated

bluntly, this implies that the temptation to use aggregate estimates

to draw inferences at the basic unit of social and psychological

organization—the person—is far less accurate or valid

than it may appear in the literature. Indeed, even the best-case scenario

is quite alarming: Only 68% of all individual correlational values

fall within a range that would be predicted by group data to cover

99.7% of all possible correlations—a discrepancy of nearly 32%.

The worst-case scenario is clearly dire: It is plausible that inattention

to nonergodicity and a lack of group-to-individual generalizability threaten the veracity of countless studies, conclusions,

and best-practice recommendations.

A strong statement indeed!

NB Ergodicity is a term that states that variability within an individual is equivalent to that within a group. Noergodicity is when this doesn't happen, as in thyroid clinical trials.

in reply to SilverAvocado

I see, so the social science students cover statistics a lot more. Does a lot of the data to be analysed come from questionnaires? Quite often with tacked on modules and courses, the surface of knowledge is barely scratched, resulting in a low depth of knowledge that isn't really worth anything in the real world. Whether that real world is industry or academia.

Blimey social theorist! Sounds impressive. Most of my statistical analysis relates to experimental and computational data. So fairly mathematical. Physical data usually measured and computational data derived from mathematical modelling of thermodynamics and fluid mechanics systems and processes. Much greater fun now my brain fog has lifted!

SilverAvocado profile image
SilverAvocado in reply to

Hehe, yes, brain fog definitely takes its toll :p I feel like I hardly remember anything!

in reply to SilverAvocado

You're not kidding! 2+2 was a challenge at one point!

diogenes profile image
diogenesRemembering

I smell a scientist! It's true: there is an enormous gap between the essential rigour of legitimate biochemistry/physiology findings and the sloppy realm of medical-based analysis. No meeting of minds, but one we are trying to bridge.

Wow! Thank you!

crimple profile image
crimple

Thanks for all you do for us Diogenes. Looking forward to reading the paper

UrsaP profile image
UrsaP

Great to hear that there is some sense going to be published. And yes, it needs to go to NICE asap.

shaws profile image
shawsAdministrator

It is great that we are lucky enough to have researchers who can come to the conclusion you and your team have as so many people aren't able to argue their case of why they feel awful whilst being told you're 'normal' and given a prescription for the symptom.

asidist profile image
asidist

just came across this article and saw it was already discussed here so thought i’d update this thread w the link:

hindawi.com/journals/jtr/20...

You may also like...

New paper on guidance for combination T4/T3 treatment

combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: a...

Advice about combination of T4/T3

else in the morning. Could you please advise if I should change something, increase or decrease...

A UK-based paper reviewing combination T4/T3 therapy guidelines

combination thyroxine (T4) and triiodothyronine (T3) hormone replacement in clinical practice: A...

Why the Hesitancy in Recommending Combination T3/T4 Therapy?

New article on designing proper trials for T4/T3 combination therapy

how to design trials for determining use of combination therapy. Naturally, being US based, it...