Well-conducted clinical trials are essential for us to advance medical care. Full disclosure of the results will improve the public’s confidence in the effectiveness of new treatments, improve participation in clinical trials and benefit all of us – but only if they really give a true picture of the results and what they actually mean.
In 2022, the Medicines & Healthcare products Regulatory Agency (MHRA) put out a consultation related to the legislation around clinical trials. The original clinical trials regulations were introduced in 2004 primarily to improve patient safety and ensure that data obtained from the trials was both reliable and of good quality . However, they were rather burdensome, didn’t really differentiate between small-scale academic trial and large-scale Big Pharma trials and simply made things more complicated than they needed to be; a change was long overdue.
At the time of their introduction, I found it frustrating that regulations imposed by the EU were foisted upon the U.K., and we had no power to write our own legislation that may have been more appropriate to our situation, perhaps allowing some flexibility for the small, ground-breaking clinical studies, led by academics, that I was involved in.
An update to the regulations was written by the EU in 2014. This new regulation (Regulation 536/2014) was more pragmatic, simplifying some of the bureaucracy, improving transparency (by including a public database and layperson summaries) and making provisions to support academic and non-commercial trials. But, in a twist of irony, due to the delay in implementing these changes and the U.K.’s departure from the EU during that time, this regulation was never written into U.K. law. However, regulation 536/2014 was introduced in the EU, thereby offering the EU a distinct R&D advantage over the U.K. What should have been an advantage of Brexit turned into a disadvantage – I hear the Remainers’ jeers!
The MHRA’s consultation seemed to be, at least in part, in response to this – not the jeers of the Remainers but the U.K.’s lack of competitiveness in drug discovery. It asked many questions relating to the existing legislation and proposed legislative changes. The proposed changes are generally welcomed, although the delay in introducing them into U.K. law is not. A comment piece this month in Nature Medicine looks at one change, which was very much supported by the people who replied to the consultation, but which may end up being quite controversial and over which I have some concerns.
The change will introduce a requirement “to offer trial findings with participants in a suitable format or explain why this is not possible”. Part of the problem, as the authors of the comment piece point out, is that it is not clear how best to implement this policy. The authors set out to propose a framework for what information should be summarised for participants, how results should be summarised and when. For example, they suggest that the information should answer these four questions: what question did the trial set out to answer? what did the trial find? what effect have the trial results had, if any, in changing treatment or prevention? and where can the participants find out more?
In the article, the authors make reference to the six-page summary provided to participants involved in the RECOVERY trial. For those not familiar with the trial, it was a large ‘Randomised Evaluation of COVID-19 Therapy’ carried out in the U.K. to try to find effective treatments for COVID-19. However, we need to be careful when we summarise the findings of such studies because the information omitted is just as telling as the information provided, and unless all the information is freely accessible for scrutiny, the information provided can be more misleading than providing no information at all.
If we take the case of hydroxychloroquine used in the RECOVERY trial, the summary says quite clearly that there was “No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19.” The evidence from the study seems to support this, but, of course, the summary fails to mention that hydroxychloroquine was never expected to be effective in patients already hospitalised with severe COVID-19; it was thought that it would most likely be useful in the early stages of COVID-19. If it had been administered earlier, in an outpatient setting, at a reasonable dose, the results may have been quite different.
An Italian study investigated early intervention in around 400 patients in early stages of COVID-19 from November 2020 to March 2021. Doctors were able to select from a range of drugs and to choose those most appropriate for individual patients. This included the use of hydroxychloroquine (200mg twice a day for seven days) usually in cases where ivermectin was not available and where hydroxychloroquine was not contraindicated (this was in approximately 30% of patients in the study). Patients in the early stages of the illness who took part in the study, seldom (8% in phase 2a) or very rarely (4.6% and 1.6% in phase 1 or phase 0 respectively) required hospital admission. The main result of the study concerned the overall mortality; only one patient died from COVID-19 (a lethality of 0.2% compared with national statistics indicating a lethality of around 3% for similar patients). So, the early intervention appeared to be effective, but the complex nature of the study made statistical evaluation difficult.
What the summary also doesn’t say is that the dose of hydroxychloroquine used in the RECOVERY trial was much higher than standard treatment. For the treatment of malaria, the standard regimen may be something like 800mg initially followed by a further 400mg dose six hours later, then another 400mg 24 hours following the initial dose and another 400mg 48 hours after the initial dose (a total of 2000mg over 3 days). In the RECOVERY trial, patients received 800mg initially then 800mg 6 hours later, followed by a further 400mg six hours later, followed by a dose of 400mg every 12 hours after that for the next nine days. So, participants received a whopping 2400mg within the first 24 hours of treatment. This is clearly going to affect the adverse event profile and impact patient outcomes. Contrast this with the Italian study where 200mg was given twice a day for seven days in the early stages of the disease.
On reading the summary of the RECOVERY trial relating to hydroxychloroquine, you would be forgiven for thinking that hydroxychloroquine had been shown to be of no use in the treatment of COVID-19. In fact, the UKRI headline summary simply states “Hydroxychloroquine has no clinical benefits.” The situation of hydroxychloroquine (and similarly ivermectin) were so highly politically charged that fair reporting of studies was practically impossible. The summary presented was quite misleading in this case, and I can imagine many similar scenarios where the summary would fail to tell the whole story.
However, this is just one problem. Another problem relates to how the data is presented, since it is easy to show one thing when the actual data shows something different. To really understand these problems, I’d suggest reading Prof. Norman Fenton’s paper on the Simpson Paradox. In this paper, he clearly shows how results can be presented, very plausibly, in such a way to show that a drug is more effective than a placebo, even when it isn’t. Similarly, if you want to see his detailed analysis of the illusion of the efficacy of the COVID-19 vaccine and other similar data, then I suggest looking at Prof. Fenton’s website.
A further problem touched on in the paper relates to when the results should be made available. Some might say “as early as possible”, but I see problems with this. Firstly, this doesn’t give an opportunity to fully investigate the long-term safety and efficacy of a new treatment. Secondly, to really understand the full impact of a study, it may take many years. For example, if you are looking at the outcome of a certain cancer treatment, you may need to wait 5-10 years (or more) to really see if one drug was more effective than another (time to relapse, for example, will hopefully be many years ahead or not at all if the drug is really good). So, presenting results early (which happens all the time in the published literature for obvious reasons) may give an untrue picture of how good the drug really is.
Public engagement in clinical trials is really important. It can help inform scientists about their proposed studies, provide insights that we, as scientists, don’t even think about because we are caught up in our own little research bubble, and improve the study significantly, thereby improving outcomes for patients and strengthening the results of the trials. Participants in clinical trials should have the right to see the results of the study, so I wholeheartedly support the proposal made by the MHRA to be more open with the public in reporting results of studies that they have been involved in. However, I would go further and propose that all the data is easily accessible, warts and all, so that the results can be properly analysed, and the true effectiveness of the study drug assessed independently. After all, although the information about the drug is confidential to the company, they are asking the general public to take part in studies, so the general public has the right to know the outcome of the study. If that is a step too far for drug companies, then I would suggest that the summaries should be written by independent scientists with full access to all the data so that a fair unbiased summary is presented. I’m not even sure if that is possible anymore but I live in hope that we can get full disclosure on the results of clinical studies so that we can all know if the drug is truly beneficial, to whom, in what setting and at what dose. Although we’d all like to put a positive spin on our results, this isn’t usually in the public’s best interests. As the authors of the Nature Medicine comment note, “Communication of trial results must happen whether the trial has positive, inconclusive or negative results.”
Dr. Maggie Cooper is a pharmacist and research scientist.
To join in with the discussion please make a donation to The Daily Sceptic.
Profanity and abuse will be removed and may lead to a permanent ban.
I fear that Boris will delay, or only partially reopen, because of SAGE scaremongering. My guess is after a week or two of small rises (coinciding with infections from the bad weather period a week or so back), the end of June will show falls again leaving SAGE proved wrong. There will be no significant wave. If this happens, I hope Boris will finally stand up to the lockdown maniacs on SAGE and remove them.
‘When prophecy fails’
Despite the fact that their prediction did not come true, they will come up with an explanation that proves they were actually right
That’s how cults work
I fear that your spelling is a little awry in the last sentence.
Yep – they have, after all, had decades of practice after many, many failed global warming predictions!
Oh dear … that last sentence is a sad reflection of hope over experience!
For God’s sake, clamp
down on these SAGE fanatics!
Surely if the govenment wanted to “clamp down” they just would but seemingly they are “just not” .We didnt vote for scientist and yet they are running the country what sort of democracy is that again ??
Every member of the lockdown skeptic MPs should shout and demand “what metric will end this? If not in high summer with 80% antibodies, when Mister PM? What is your key measure that means we are free? If you don’t have one how do you know you have not just made a wrong decision?
Last July I wrote to my MP and to the PM questions email this simple question:
“When will mask mandate be removed. What is your measure of success? Can you tell me this will ever end? If so, how will you know? If not, tell us this is forever.
Got no response. No surprise.
Many metrics have been used
They just move the goalposts and a compliant media, non existent opposition and dozy, brainwashed public don’t notice
Don’t give up. I have 3 replies from 18.
just stop wearing it.
I am sure there will be a wave in the winter though
I suspect many of those who had the first jab have not gone back for the second
Only anecdotal, but many were made ill by the first jabs
Nearly everyone I have spoken to reported severe headaches for months after the first jab
Also many believed they would have their freedom back and go on holiday etc and have now realised they were lied to
Threatening to cancel the 21st is just part of the psychological warfare being waged by the dictatorship against the people
I’m sincerely hoping that when they try to wage war on the uninjected the reality is that rather than being the experimented on vs. the sceptical (what they hope) it’ll actually be the ruling classes vs. those who feel betrayed.
If “they” can actually stop being greatful for a few moments
I suspect most who had the first jab went back for the second.
Many were made ill by the first jab, but nearly everyone I have spoken to has had their second jab.
Nobody I have spoken to had headaches for more than a day. And I work with ardent covidians who jumped at the chance to get a vaccine.
Many did believe they would have their freedom back and have realised they were lied to, but overwhelmingly they believe they are stopping the spread of a virus that, if not as deadly as was first thought, has proven to be seriously annoying and inconvenient.
I don’t disagree with your last line.
If you feel lousy after your jibjab, be it 1or 2, it’s a aign that it’s woooooorking.
Yes and if they do get ill after being injected, well, they would have been so much worse if they had declined it, so thank goodness they took it to stop you from being unwell…
Sir, I have a close friend, much older than me and I did my best to dissuade him from having any of the experimental vaccines but he had his regardless.
To prove his point he’d told me he was fine however this weekend he revealed he’d lied to me, suffering a mild unshakable headache for over two months.
Of all those I know, and it is most of my family and friends all but one had unpleasant side effects, ranging from bad headaches, shivering, vomiting, having to book leave prior to the second vaccine to prepare for the side effects, rashes, shaking, unable to sleep for several nights, aching joints. None of these were reported to yellow card because no one knew anything about yellow card.
I have been conversing with an acquaintance; I have just been made aware he has had months of somewhat similar side effects, he has made a report to Yellow card but had to have 4-5 different Doctor’s appointments & various treatments to get someone to do it – for sure, he only found out about this reporting system via dogged persistence and self research after the fact, was definitely not told anything about this during his vax appointment, nor of the fact that the procedure is still experimental in trials phase.
I said I’m not totally sure what his options are – other than that going to the National press is a waste of time, local press possibly might print something. maybe a complaint to the GMC, because they almost certainly have to give that due consideration. He did say that he considers that the Healthcare worker did not provide adequate informed consent, and is considering options, including whether to pursue some kind of formal complaint, or even criminal negligence charges.
You don’t need a dr to do it, you can fill in a Yellow Card report yourself. Details I think are on the leaflet you get for the jab, but I bet they’re online too,
I think he meant that it took that much for the person to realise the need to finally report it.
Radical old me says there are a few dozen people running this shit show .There are millions of people in this country whi would like it to stop all they have to do is protest and voice their anger and maybe miss yoga on saturday morning but they /we shrug and say”what can we do” They/we are to blame for convincing an icompetent government that it is competent based on the level of complaince to its knowingly dodgy ideas.
The country simply has to stop getting jabbed, stop having tests, stop wearing masks and start hugging all and sundry.
No sign of that happening, sadly.
Ok, we start now.
Could well be anecdotal. Self n OH have had both jabs with no side effects at all
An interesting forensic examination of SAGE’s turds that they are so keen to leave all over the piece.
One thing :
“The 85+ age group has fallen from about 22% of the total admissions in October 2020 (139/645) to about 14% now (10/69). This is being attributed to the success of the vaccination programme in preventing transmission to the vulnerable elderly – that sounds like a plausible explanation to me.”
Another explanation is that the January peak brought forward a proportion of vulnerable elderly mortality, resulting from vaccination. The 8% figure sounds about right for that thesis.
Why anyone lends SAGE credibility after all their crap forecasts is beyond any rational explanation. The whole crew needs to be thrown under a bus. Rapidly.
Exactly. The DNR’s on elderly patients, & jabbing programme (inc. allegations of at best, not completely ethical coercion, in care homes), combined to ensure the numbers in the 85+ age group are not what they used to be!
The jab does not “prevent transmission” it only claims to mitigate the effects of the virus.
SAVE are either fools or liars.
Boris is, of course, both.
Perhaps so, but he is the properly elected leader of the nation. It is time to have him act on advice and needs beyond SAGE. He needs to lead. At this point pray, do a rain dance, or stick pins in your Boris voodoo doll that he does the right thing!
May he finally be a broken clock at just the right time!
Yes because ive heard that the “vaccine” actually works and that we are no longer strictly in a pandemic in this country.Ive also heard that because of this terrible situation we should postpone “Freedom Day” My basic education can not make sense of these two seemingly opposed outcomes .Im off to wash my mask and keep my hands two mwtres apart and save the NHS
BoJo just goes which ever way the wind is blowing. He’s just weak.
He has directed SPI-B to frighten the British people
A democratically elected government has waged psychological warfare on its own people
He’s more than weak, he is evil
Spineless coward, if he defers to someone else he doesn’t have to take the blame and if he picks the safest course, same deal. I hope it’s that but it’s getting harder to ignore the potential for malice rather than ignorance.
Boris knows exactly what he is doing – every step of the way.
The major question is whether Boris sees data displayed like this (especially comparisons to SAGE projections made without anticipation of a new imported variant). They have been wrong, not a little but significantly since March 2020. There is growing evidence that harsh lockdowns that extended into June last year aided in our winter spike. A harsh lockdown based on projections that were wildly wrong. I supported the January lockdown to provide space to jab all vulnerables (done and dusted, to the point where I in my 50s am now doubled jabbed). Those who refuse cannot sway policy. You do not need 100% compliance to attain social immunity. Look at the data Boris. Talk to those outside SAGE. Do not listen to communists social scientists who don’t belong on SAGE to begin with.
Masks must end! Social distancing must end. It’s summer. Use the natural seasonal benefit (well established for all aside from SAGE modelers) to your benefit. Yes, people will still get sick. Yes, some will die. But they are dying of many diseases, including suicide and hopelessness. Give us back our world! Covid is now, thanks to the vaccine, less deadly than seasonal flu. We would never be forced to wear masks and avoid others for seasonal flu. It’s time to look forward, not back!
SAFE MEANS NEVER!
Why is such a beautiful piece of common sense constantly ignored and ridiculed?What happened to our population.After all im sure you are only one of thousansd to share the same opinion.
If the PM doesn’t see data displayed like this he is not doing his job
It’s the job of leaders, bosses, decision makers to question experts and measure their performance
Basic stuff
He’s either useless, wicked or both
The reduction in death figures is not due to the experimental vaccines which have caused deaths, its the seasonal corona viruses demise due to the approach of summertime.
In addition, the tinder had been burned last year.
Yes I agree and I don’t think the vaccines can be tested properly until winter comes
Tested? How can you do a meaningful test when relevant data is not collected, or is deliberately obfuscated?
Agreed. Far too much blind faith being put in the vaccines being the sole cause of the decline in cases/deaths/whatever. Flu comes and goes every year without mass vaccination or lockdown, why the hell should covid be any different.
Just wait until the ADE’s kick in – then it will be an almighty sh1t show.
Got to keep that fear up, how else you going to explain the 5 million on the waiting list, the crashed economy and the joblesness thats going to follow in October.
Anything so they don’t have to face up to what they have done and take the blame
Surely though at some point they will need a point, a frame, from which to begin a climb down .Even in all this chaos their time is ticking down ,they will at some point have to be seen to do something approaching conclisive ,surely ?
I’ve been thinking that since May 2020
The UK govt and the psychopaths egging them on may not be good at much, but they are good at boiling frogs
Exactly.
Seems that the only reason for not reopening and fearmongering is the lazy and corrupt NHS doctors vacation plans.
?
Love of power, arse-covering, sinister motives. The largest portion of blame lies with the PM and the Cabinet. They are in charge.
It’s the BS variant.
Nothing more, nothing less.
And one of many still to come.
Cases, cases… they may be rising but so have tests. Current positive rate is 0.3%. I am not sure what Ct values are being used but this figure is probably well below the false positive rate. Its just noise, how many have symptoms? Its clear above, few need hospitalisation.
How many people have colds at the moment? Well, speaking personally – me last week, my son now, my niece, my mother. Are we getting tested for it? Obviously not. Given there’s 4 of us living all over the country who have had it at the same time in my family alone, 4000 cases of covid a day in a population of nearly 70 million is just not worth discussing.
I wish the NHS was on a knife edge, shower that it is.
I have commented before on here that it is high time the NHS was put out to pasture. The resultant tax saving could then be passed on the taxpayers in the form of tax cuts. People could then use the money to purchase very good private healthcare.
Another advantage of this is if the provider you choose turns out to be no good you are free to take your money elsewhere. You have no such choice with the NHS.
How can anyone still think this is about public health and not about public control?
‘It does not matter if the numbers of positive tests rise in the community as long as the hospitalisation rates remain low. My interpretation of the published information suggests that is the case.
So why are the Government’s advisers saying something completely different? I can only think of two broad explanations. It is possible they have information that has not been released to the public for some reason. Or they are selectively interpreting the known information to support an undisclosed agenda.’
What could that agenda possibly be?
‘…..using psychological remoulding as a tactic for political hegemony’
‘……revolutionary ideals had to be protected from weeds of doubt by vigorous assertion and mass coercion…….people were attached to the new order primarily through terror or emotional appeal’
https://jsis.washington.edu/ellisoncenter/wp-content/uploads/sites/13/2016/05/dome_REECASNW.pdf
The title of this referenced article?
A Timid Flock: Investigating Propaganda Under Stalin
Plus ca change……..
Every single member of SAGE needs to be Minecrafted