Paxlovid, evidence base?

my warm welcome to today's talk it's Wednesday the 4th of May now I want to look at Pax love it today which is the Pfizer antiviral drug this evidence has just been published that it is not efficacious for post-exposure prophylaxis and despite being actively promoted by the the White House current covids are for example I'm not convinced that the evidence that it is efficacious in current populations is there at all and we'll look at that and you can make your own mind up about it and then on a completely separate Topic at the end of this video I want to look at the the possibility that some cynical people are seeing of senior officials having a vested interest in drug sales uh completely different different topics so if you just want the Pax love it bit of course just stick around for the first few minutes now um at the moment let me just uh show you this is this is the paper this is the original paper here that the uh the Pax love it data is uh based on and we'll be looking at this uh shortly it is it is a good quality uh paper but here we are here so this is the the Pax love it uh perhaps love it of course it's the end of the antiviral right um now this the the the paper that promoted the uh FDA Food and Drug Administration emergency youth authorization is the one I've just shown you it's based on that paper do always check it out for yourself don't uh take my word for anything if what I'm saying is not based on the evidence then reject reject what I say because we have to be evidence-based now this is part of What's called the Epic HR trial now all trials these days seem to rather have to have Snappy acronisms no matter how much the words have to be contorted to fit into the initials but this one's actually not too bad so it's a valuation of protease Inhibitors that's the type of drug it inhibits the proteases that makes the viruses work for covid-19 in high-risk patients epic HR now very good study this one here um or uh very comprehensive study um it had uh 1 120 patients received the uh let me try and get this right uh no matter I guess you can pronounce that in different ways plus retirivier which is a known antiviral anyway so the combination of this uh material via and uh retirivier is PAX love it the combination is packs love it so they had 1 200 patients in the intervention group who received the active treatment uh they had 1 226 patients in the placebo group they compared the two perfect that is good science double blind randomized controlled trial now the relative risk of this they found the difference between the two groups the relative risk now of course the relative risk is the risk of this group relative to this group not relative to the whole population so the relative risk a progression to severe covid-19 89 lower than the risk with the placebo so this group here had a 89 percent less chance of going on to developing severe covered but that's compared to this group here but that's normal that's how this is often done right you're always done virtually always done the absolute risk so if you're just a person who's got the uh the qualifications to get into the trial your chances of developing severe covered overall were 70 percent in other words we would hope that the other 93 were making an eventful uh natural uh recovery uh but it went down to one percent would I have that yes that I would accept that risk but then we have to look at when this trial was done and a bit about this trial to put this in some sort of context now now here we have the a bit of data from The Trial this was done in people that were already symptomatic and they were unvaccinated now this is the key thing here these people were unvaccinated they had not been vaccinated they would presumably have very little immunity or no immunity at all if they hadn't been exposed to the Natural virus non-hospitalized adults but the key thing is these were unvaccinated people and they're at high risk for progression to severe carbon-19 disease so these were people that already had risk factors so there were higher risk individuals not everyone this is not the whole population so they took unvaccinated anti-risk individuals these are the people that are by far at highest risk but of course now most people are vaccinated now most people the vast majority of people have been exposed to the virus naturally therefore have got this double immunity or immunity some people have got immunity from the vaccine some have got people from the some people have got immunity from the the virus itself some have got this combined hybrid immunity in the UK it's over 99 percent I've now got this immunity in the United States it's also very high numbers so no I'm not going to use the word cherry-picked but um you know this was a select group of patients unvaccinated non-hospitalized risk of progression to disease and we noticed that this was during the time of the more pathogenic Omicron variant 16th of July to the 9th of December 2021 so that this isn't sorry did I say Omicron this is not the Omicron time this is the Delta time this is the more pathogenic Delta not the current Omicron that we currently have at the moment and also during this time of course way less people because this was Prior Omicron way less people had been exposed to the virus at this time therefore way less people had had the opportunity to develop natural immunity way less people so times have changed um if unvaccinated people and previously infected people are partly protected and it's reasonable to assume they are then more people would need to be treated to prevent one adverse event now my understanding from the guardian article we looked at yesterday is this is 530 dollars for a five-day course so if people are now more protected than they were if Omicron is less pathogenic than uh than Delta we know that is then how many would you need to treat to prevent an adverse offense event a 10 well that takes it up to uh takes it up to that much doesn't it uh would you need to teach a treat 100 well that would take it up to that much per case would you need to treat a thousand will that take it up to that much a case can you see we're getting on to pretty serious money now um and is this the best way to spend money is the question now if I was a press release of the uh the fifth of November but just before we go on let's make it quite clear what I'm saying here is that the population now is more immune than the population this was tested on so why isn't this trial repeated now this this is the key thing if we repeated the trial now would have the data but is it is it logical to extrapolate because we're supposed to be evidence-based it's logical to extrapolate from one to the other as the White House seems to be pushing um the pushing's maybe not the right word that sounds a bit steppenwolfer-esque doesn't it um promoting promoting would be a better word promoting uh the clinicians to prescribe more Pax love it but is that based on evidence well I'm not sure that it is because it's based on previous populations and of course we don't have a previous population we have a we have a current population with much higher levels of immunity so we really need data for this why isn't that trial being done um so fire is a press release 5th of November 2021 this was about the original paper our antiviral candidate has the potential to save patients lives well it did then hopefully now we don't really know now reduces the disparity of covid-19 infections indeed it did do that and eliminate up to one uh they were and a limit up to nine out of ten hospitalizations that's true that's true providing the patients were symptomatic unvaccinated non-hospitalized adults at risk at risk for progression to severe disease in that case during this time period that was true it was true at that time period and here's the press release from Pfizer that dealt with that at that time now naturally all the links are here so you can check out uh what I'm saying is is accurate now Pfizer shared in vitro now another argument here as well we've moved on from uh Delta to Omicron um is this drug likely to work with the Omicron variant so there's evidence that it worked with the Delta variance in terms of the pure um pharmacodynamic effect of the drug the antiviral effect of the drug is it likely to be effective against uh Omicron and that's what this uh this that's what this press release is about I think here um yep that's this one um against Omicron variant effective against Omicron variant now again the information is there we don't like science by press release um but it's what we've got at the moment um but let's look at some of the things now the studies here are done uh in vitro in vitro this is not an in-life study it's not an in Vivo study um it's basically a bench-based study and uh these are the references for it the results show that in all cases that the uh no material there um showed all cases that monitor of it was a potent inhibitor of its Targets in other words it still worked as this protease protease inhibitor so that makes that makes perfect sense now um this is only uh an in an in vitro study no it's not in Vivo it's not in life it's an in vitro study it's not not peer-reviewed publication but I do believe it because pharmacologically it makes perfect sense that you wouldn't expect the enzymic systems to work differently in the Omicron as opposed to the Delta so I'm quite happy to accept that so that gets uh that gets a big uh I guess a big tick we'll accept that what we don't accept is that this evidence applies to the population now so it's not the virus that's different now so much partly it's that the population is different now population is more immune now so we need data to make this evidence-based now in terms of um this is the latest release in terms of um post-exposure prophylaxis so that's on this one here again again science by press release don't like it but no reason to particularly question it and let's just summarize what this is saying uh does Pax love it work for post exposure in other words you're in a household someone's tested positive you protect the other members of the household that will be post exposure preflex profit like sort of infected person in the workplace you protect the other people in the workplace now here the evaluated data from 2957 adults that is a good sample size a Pfizer observed a reduction of 32 percent of a five-day course and a 37 in a 10-day course but you could say it was a bit naughty of them to put that in really I'm not saying that but some people might say they're a bit naughty to put that in because these results this is a direct quote however were not statistically significant now if it's not statistically significant that means there is uh we must assume that there is no difference between the groups not a statistically significant in other words these numbers uh 32 and 37 reduction mean nothing because they didn't reach statistical significance and with this kind of number you would expect statistical significance because that has a large sample size and as such the primary endpoint of reducing the risk of confirmed and symptomatic covid-19 infection and it had also have been exposed to the virus through a household contact was not met in other words it doesn't work as a post-exposure prophylaxis so there we go it's not working as a post-exposure prophylaxis and we don't have data to tell us whether it's working on the current populate population or if it is working to what degree it's working this is a study that should be carried out I suspect Pfizer can afford to carry this out so it would be good if they did now this is the um this is the Pfizer uh Pax lovered information sheet for patients here now I just put this in to point out that um no drug is completely safe if everything anything is going to work there is an element of risk so uh Pfizer here pointing out that uh Pax love it is not FDA approved a Pax love is an investigational medicine uh some mentions May interact with Pax love and cause serious side effects so it must only be prescribed by someone who's medically qualified uh nurse practitioners doctors I don't know I don't think pharmacists are prescribing this because you've got to take into account the interactions with other medicines if you take too much packs love it they're worried about that called the emergency room um so all um good of them to tell us these possible side effects allergic reactions could result in trouble swallowing or breathing swelling of the mouth lips face throat tightness hoarseness skin rash liver problems tell your healthcare provider right away if you get loss of appetite yellowing of your skin various side effects these aren't that surprising but um that they are they are spelled out by the government other possible side effects so that there's potential side effects here so what what we have is a drug with uh many potential side effects that is I would say phenomenally expensive it's certainly of retreating thousands or millions of people for which I don't really think we've got evidence for the whole point and the FDA has made a big song and dance about this to put it mildly about things needing to be evidence-based and yet it here promoting something which we don't have evidence for in the current population we only have evidence for it in the previous population uh during Delta times in people who were less likely to carry natural antibodies before Evolution or depending on your perspective the creator of evolutionary processes provided um the Omicron variant to produce Mass uh stimuli stimulation of our immune systems all over the world as we potently saw Illustrated in the reports from Uganda so anyway so that's the end of that bit now completely separate uh topic I'm just going to tag on to the end of this video here um so this is Dr jar the White House covid-19 coordinator as we said Pax love it uh he wants to push to reach the vulnerable it does actually say that I think that's the New York Times article so they actually say push that's a bit steppenwolfesque isn't it um we said we were provided and said promote anyway so they want to push it to reach the vulnerable uh doctors are too isn't to prescribe the drugs so they're being encouraged to prescribe this drug but based on current evidence we'll put a question mark on that um now uh Dr jar um according to this well-known Source here Wikipedia may be completely wrong if you read my Wikipedia article it's a bit funny but there you go um uh was seen or was uh is I think was I don't think he is now uh I'm not really sure but he was senior advisor at all Brightstone house group um The Firm advises clients on International policy and Global markets now some of you may prefer your senior medical advisors not to have a potential no no one's saying it's a conflict of interest of course but a potential apparent conflict of interest is a cynical person might view it some of you may prefer that uh personally I have no uh Financial interests in um pharmaceutical Industries and all of the nurses and doctors I work I've worked with um on the front line none of them knowing I've known have got these interests uh Financial interests so it's a picture that very senior people sometimes appear to have a potential conflict of interest no one's saying that would result in them promoting a particular drug of course not but it's an apparent conflict of interest you can decide you don't need me to tell you what to think do you uh Patrick Valance our chief scientific officer 2012-2018 president of research and development at Global Pharmaceuticals GSK uh we believe is well we don't believe it's been reported in the telegraph that is cashed in five million pounds worth of shares I mean five million pounds this is this is more than you would expect um what a way way more than you and me can most of us could hope to earn in several lifetimes it's a huge amounts of money and yet these people are making um decisions about the health of the entire population again no one's saying that there's any um ill practice here but some of you might think it doesn't look good some of you might even suspect it does affect uh does affect decision making that's not for me to say um now this is from the uh this article here is from the uh British medical journal future jobs of FDA Hematology Oncology reviewers um check out the references for yourself more than a quarter of the Food and Drug Administration Employees who approved cancer and hematology drugs from 2001 through to 2010. left the agency and now worked for uh or consult for pharmaceutical companies now no no one's saying that they anticipated this move and therefore would take decisions which might make them more attractive to a future employer um but some people are uncomfortable with what is seen as the uh what do you call it that door that spins round and round the rotating door whatever you call those things um yeah some of you might be uncomfortable with that and of course people senior people can move from pharmaceutical jobs into Administration decision-making jobs and then potentially back into pharmaceutical jobs again um so so perhaps it should be a criteria for senior appointments that they are uh have no apparent uh Financial interests as you say completely separate uh topic to the when we looked at the front at Pax love it that is purely about the evidence so what we need is a randomized double blind control now please uh from Pfizer examining the effectiveness of pax love it in the currently Uh current population which is highly vaccinated and uh highly exposed to the uh Omicron variant then if recommendations are still made they would be based on more current evidence which would be good because we want to be evidence based and I was looking at the wrong camera then so apologies for that and thank you for watching

Channel: Dr. John Campbell

Views: 438,744

Keywords: physiology, nursing, NCLEX, health, disease, biology, medicine, nurse education, medical education, pathophysiology, campbell, human biology, human body

Id: iax-dL7F3qw

Length: 21min 17sec (1277 seconds)

Published: Wed May 04 2022