I found the apparent Spanish policy that Grannajan mentions an interesting one.
My first reaction is that I would as an immuno-compromised person not object to it, provided the level of antibodies below which Evusheld was given was not absurdly low. Aware that the NHS budget is finite, I can see the point, because using funds to provide Evusheld for someone with abundant antibodies would be an unnecessary expense, and an antibody test is I believe much less expensive than an Evusheld jab. Perhaps I have missed something?
Does anyone else know more about the Spanish or other health service criteria for who to provide Evusheld to, in those countries that have procured it?
Others following this issue may well aware that Steven Barclay, while Secretary of State for Health etc, finally replied (https://bloodcancer.org.uk/documents/444/1417253_-_Gemma_Peters_and_others.pdf) to the open letter of 19 charities led by BCUK making the case for prompt provision of Evusheld ( Leading charities and clinicians urge Government to secure Evusheld | Blood Cancer UK ) . Of course the letter defends the decision for non-procurement, but it does give more of the rationale on which the decision was based than I think was available previously. I aim to think through and inform my reaction to this carefully, but hope that BCUK or someone reading this post might be able to answer two questions that hamper me or anyone else doing this:
The response is stated as being to “letters of 28 July and 23 August on Evusheld”. I found the July 28th letter posted on the BCUK web site (Leading charities and clinicians urge Government to secure Evusheld | Blood Cancer UK ), but not the 23 August one, which is the one referred to most in the response. Does anyone know where I can find it?
The source of the reasons given for non-procurement are stated as being “RAPID C-19 and a UK National Expert Policy Working Group as well as DHSC officials”. There are direct quotes from some RADIP-C19 document, but although a link to a description of RAPID-19 is given, I found no links there to any reports from it. Again, does anyone know if this report or information about the Expert Policy Working Group, is accessible?
There is a current Freedom of Information request into the DHSC asking for details on the Expert Working Group involved in the decision- response due by 25 Sept - a prior FOI request showed that EWGs do not issue minutes or notes from their meetings (unlike Expert Advisory Groups which are more permanent and do issue notes)
Hi @Ben ive been following the goings on with gov and Rapid Cov 19 etc many items on Twitter @Martin24051921 if your not on that let me know. In short, answer due some time this week on why gov said no to Evusheld. Rapid Cov 19 oversight group report to CMO will be on NICE website The COVID-19 Antivirals and Therapeutics Taskforce - GOV.UK
Thanks, MCA. I use twitter little but did log in and found your posts helpful. However, I find that I (benedictarms1) am now blocked from seeing them. I hope I have not inadvertently done something to raise suspicion of some sort (I haven’t posted anything).
Thanks in particular your posting various recent government documents in your twitter messages, I felt informed enough to write the following letter to the office of my MP, Daisy Cooper, who is leading the 30 min Parliamentary debate on Evusheld on Wed 11 am:
Dear Will
I am following two previous messages to Daisy and yourself, after noticing that Daisy is leading a debate on procurement of Evusheld next Wednesday. To recap about myself, I am one of Daisy’s constituents and severely immuno-compromised, and have been following the Evusheld issue intensely. I am also a Professor of Epidemiological Statistics so quite experienced in judging evidence of the type central to this debate.
I am sure Daisy has a good idea what best to say and has various sources of advice, but I thought it worth noting at least to those advising her the issues that seem to me key, in particular following the very recent publication of the RAPID-C19 report to the CMO on evusheld procurement
The key issues seem to me:
It is reasonable to note, as the RAPID-C19 report does, that because the randomised controlled trial (RCT) which identified the effectiveness and safety of Evusheld was before the time of current Covid variants, this leaves some doubt is to it effectiveness against current variants. However this has been true of all of the immunisations (Pfeizer, Moderna, Astrozeneca, …) rolled out to great effectiveness for those able to respond to them – not as effective as with the original strain, but nevertheless very effective. Very often judgement of the likelihood that treatments will prove effective in one context will also be effective in another needs to be made based on evidence other than RCTs. Absence of such direct totally comparable RCT evidence has never been a reason to presume that a treatment is not worth giving.
For Evusheld there is an abundance of evidence beyond the RCT indicating at least some effectiveness against variants other than those current during the RCT.
General consideration of mechanism – in particular evusheld includes two antibodies precisely to increase likelihood of effectiveness against a variety of variants.
Laboratory studies of neutralising ability of Evusheld against Covid variants. These have indeed shown reduced effectiveness but overwhelmingly still a substantial degree of it. At least to an extent this can be addressed by increasing the dose, as advised by the US FDA.
Real-world observational studies of populations of immuno-compromised persons treated and untreated with evusheld. Several have been published and noted in the RAPID C19 report to the CMO and they overwhelming find, as did the laboratory studies, that with populations experiencing omicron (albeit mainly BA.1 and 2), evusheld retained effectiveness though at a reduced level. The RAPID C19 report lists various limitations of these studies which in general I thought indeed indicated a degree of uncertainty on conclusions from the studies. However, that is true of any observational studies and not a reason to give no credence to them at all. The report does not identify any fatal flaws in the studies.
For any medical treatment there is a weighing-up of likelihood of benefit against that of harm. An uncertain substantial benefit would be reasonable if likelihood of harm was low. For evusheld harms were of course evaluated in the RCT and no significant ones found. Indeed neither the RAPID C19 report nor Barclay’s response to the petition or charities letter mentions specific medical harms, though the RAPID C19 report Appendix 2 (a report dated 30 May) states “‘the risks of proceeding to patient access are considered to outweigh the risks of not providing this treatment in the current pandemic context”. That conclusion seems to rest on two concerns:
The safety of the higher dose considered needed for omicron has not been evaluated in a trial. This has some merit, but it is of note that the US FDA, doubtless on the advice of their experts, did not consider this a plausible enough cause of harm not to advise using evusheld.
“The risk of deployment leading to behaviour change that increases the risk of exposure to the virus is too great when evidence of its clinical benefit is not sufficiently robust” (RAPID C19 App 2). I find this condescending and not evidence-based. Immuno-compromised persons have minds, and if we are advised that a treatment is likely to reduce risk but may well not eliminate it, we can measure our response accordingly – mixing a bit more but not willy-nilly. Again, the same applies to vaccines (for those not immune-compromised): they are very likely reduce risk of infection and in particular serious disease but not eliminate it, and people know it.
Many medicines regulation agencies (including the UK MHRA, the European Medicines Agency and the USFDA) have licensed evusheld and many other countries have procured it and continue to use it, while having access to identical evidence to the UK government. In particular those counties include the USA, which has a stringent evaluation process. This casts doubt on the certainty of the reasoning leading to the RAPID C19’s conclusion.
NICE has today (16 February 2023) issued draft guidance for public consultation which does not recommend Evusheld for preventing COVID-19 in adults who are unlikely to have an adequate immune response to COVID-19 vaccination, or who can’t be vaccinated
Thanks for spotting this Maureen54 . I do take hope from it. I suspect that the “Evusheld2” referred to in the article is that being trialled in the SUPERNOVA (Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies) trial currently going on. Lab evidence seems to suggest it would be effective against current variants.
There is a rather technical description of the trial on the web site Study Understanding Pre-Exposure pRophylaxis of NOVel Antibodies (SUPERNOVA) - Full Text View - ClinicalTrials.gov . This specifies the “primary completion date” as 29 Nov 2023, so I am not sure of the basis for article quote that astrazenica hoped that it would be available in the UK by “the second half of the year”. Still, I definitely see this as a glass half full.
Like many of us I was very frustrated by the government not authorising Evusheld when other countries did. I do however agree with NICE that by the time that they finally evaluated it, it seemed unlikely to be effective against the variants then (and now) predominating. The NICE report’s quite strong advocacy of faster procedures in future was somewhat encouraging that the process for “evusheld2” will not be similarly delayed until future variants make that one ineffective.
I see the NIHR have announced the launch of their Stravinsky study , which will look at antibody response in various immunocompromised groups. My guess is that the findings will be used by DHSC to scale down or expand the cohorts eligible for future prophylactic treatments like Evusheld2 or potentially vaccines too.
