Normally one of the possibilities of regulatory oversight is that you go into a meeting hoping your drug is approved, but the regulators are concerned about X. "Go away and check X" says the regulator, "this isn't a No, but it also isn't a Yes, we want to understand X before we decide". Maybe it'll take 12-18 months to set up and run experiments to answer X.
Regulators can decide they're uneasy about potential for birth defects, or side effects with particular other drugs you never tested, or any number of issues. Sometimes a pharmaceutical company just hoped not to be asked, and other times the concern comes out of the blue.
But if we're fast-tracking approval, anything that isn't a red flag won't get in the way. That unavoidably means higher risk to patients overall. Since the virus kills a lot of people every day everywhere it hasn't been eliminated it makes sense to take that risk, but governments (accountable to their citizens) get to decide that, not drug companies.
That's not happening, what will be accelerated will be regulatory approvals and reviews, not clinical trials.
The trials are most certainly accelerated. Take a look at Moderna's trial of their RNA vaccine.[1]
It's a 2 year trial, but data is collected on a rolling basis. They aren't waiting 2 years for final results, I'm guessing they do a few interim analyses until they see the two arms split in terms of infection rate. Then they'll go to the FDA and see if that's sufficient for approval.
And look at the N-size. 30,000 people for a drug that will be given (potentially) to billions of people. To make a comparison, Gardasil, the HPV vaccine was tested in ~28,000 individuals over 3-4 years.[2] And Gardasil is used in a much more limited population than the Covid vaccine will be.
> And Gardasil is used in a much more limited population than the Covid vaccine will be.
(It wouldn't be HN without a splash of pedantry; apologies in advance.)
I'm curious what you mean by this. Women constitute slightly more than half of the population, no? There are probably billions of women at this point who have had Gardisil administered.
270 million doses worldwide to date, of those 100 million are in the USA. The full course is two or three doses depending on age, so that's somewhere between 90-135 million people fully covered.
And it's not limited to women now. Different countries have it approved/covered for men of different ages. I (as a man) recently finished the full course, though I had to pay for it out of pocket.
So Gardasil is only approved for "girls and women 9 through 26 years of age". Plus there wasn't much expectation of use outside of Western countries initially since it's not cheap and there are likely higher priority vaccines in developing countries (i.e. do you spend dollars on this or meningitis vaccines?). Use is probably pretty broad now, ~10 years post-launch.
Eventually they expanded the label to include "boys and men 9 through 26 years of age".
So all in all, a relatively small slice of the population, where for the Covid vaccine, they're trying to get it approved for pretty much everybody.
The FDA doesn't do clinical trials for vaccines. This is unique to vaccines in US drug regulation. Vaccine manufacturers self-certify and send a report to the FDA, who signs off on it. They can certainly choose to rush clinical trials in the current environment and probably still have their report signed off on by the FDA.
> Oh, and by the way, we want you to rush your testing so you don't have the normal time to verify its safety!
This! The public are acutely aware of the predicament that governments have created and most will be very skeptical of a vaccine that's been rushed through like this especially if a regulator says 'sure its totally safe' when we can all see the data to determine that cannot possibly exist in the near future.
Depends on the relative risks. I can imagine an 80 year old in a US nursing home jumping on the barely tested vaccine while a 23-year-old New Zealander waits for more information.
The problem is that others will have to take the vaccine as well. Not to protect themselves, but to protect others. It would be nice if they could do that without (fear of) risking their personal safety.
Every vaccine/drug can have potential side effects, possibly in the 1 case to millions of doses. There's no such thing as a non-side-effect product.
However today there are ready armies of lawyers to sue for those very rare side effects that have a much lower fatality rate than the disease itself.
Are pharmaceutical companies the pinnacle of honesty and ethics? Of course not. Would it be worthy pulling a covid vaccine out of shelves if it caused a 1 in 1Mi serious side effect? No way.
Sure, you can try to identify and quantify the risk so maybe don't give this vaccine to people who might have a worse outcome, still, nothing is perfect.
> The public are acutely aware of the predicament that governments have created
What predicament? The gov't didn't create covid.
> especially if a regulator says 'sure its totally safe'
To my knowledge (and I did work in this area) no regulator will ever declare a drug 'totally safe'.
> most will be very skeptical of a vaccine that's been rushed through like this
Yeah well, you're speaking for a rather large population whose minds you don't know so please don't. Also covid is dangerous so people may be skeptical but still take it.
Not that it’s relevant in this particular case, but I don’t take anything that’s only approved in the US, because the FDA really doesn’t care, and especially doesn’t care right now.
Most drug companies actually view the US as the beta test country in a lot of ways.
If something makes it to Australia (who are very strict on pharmaceuticals) then it’s usually pretty safe.
As someone who has worked directly with the FDA, this is an absurd position. If anything, the FDA errs on the side of causing no harm versus getting a much needed treatment approved.
And it might be good to know that most countries approve drugs based on the same data - global clinical trials. Australia is looking at the same data as the US when making an approval decision. Some countries require local trials (China and India, I believe).
In addition, there is plenty of collaboration across drug approval bodies when developing or changing regulations. They are all talking to each other to determine the best approach.
Here is a good example of the FDA and TGA (Australia) and Canada approving a new cancer drug together[1]
Several aspects of FDA regulation are widely regarded as inadequate, in particular the 510(k) process for medical devices and Section 901 of the FDASIA.
FDA approval is slow and expensive, but the political pressure to change that situation has created myriad alternative routes to market authorisation rather than a fundamental reform of the process. Far too many drugs and devices have sneaked onto the market with lower standards of scrutiny and the FDA's post-marketing surveillance isn't up to the task.
The FDA knew about rofecoxib's cardiovascular risks for years and did nothing; they've known about rosiglitazone for years and they've done very little. It's just too easy for bad products to get on the market and stay on the market under the FDA's less-than-vigilant gaze.
Several aspects of FDA regulation are widely regarded as inadequate
I think that's a matter of opinion, rather than a purely factual statement. It intersects with your comment "Far too many drugs and devices have sneaked onto the market with lower standards of scrutiny", because it begs the question "how many is too many?".
It's all a trade-off. The higher level of scrutiny requires more time and more money and can result in people being denied drugs that could have prevented harm or death.
It's my own personal opinion, but I think the FDA does a pretty good job considering the judgements they are asked to make.
And rofecoxib was eventually pulled, but only after careful scrutiny of the risk. It's not hard to do a retrospective analysis and see a safety signal. Pulling a product based on limited data means you may be doing harm by denying people a drug that helps them. Before the COX2s existed, perforated ulcers due to NSAID use weren't exactly rare.
And I'll just end with one final comment - overseeing a safe and effective drug supply is really damn hard. So I try and take that into consideration when evaluating the FDA's (or any countries drug agency) actions.
> I don’t take anything that’s only approved in the US, because the FDA really doesn’t care, and especially doesn’t care right now.
Alternatively, just don't take anything where the patent hasn't expired. Once the patent has been expired for a few years you'll actually get the truth about the dangers of the drug, because the pharma companies then need to make the old drugs look dangerous in comparison to the new ones. (E.g. why they're publishing fake data about hydroxychloroquine in Lancet and elsewhere.)
I mean if you are going to potentially die otherwise then that's one thing. But if you go to the doctor with a sore throat and they hand you some random script for something you've never heard of, hard pass is a pretty good strategy.
The appropriate way to make medical decisions is based on data, but if a drug is still under patent then the data isn't there.
> Most drug companies actually view the US as the beta test country in a lot of ways.
This is mostly wrong, except maybe for vaccines. The EMA, for example, has vastly lower regulatory requirements for most drugs than the FDA. Many sources actually estimate that, on net, the FDA has killed more people than it's saved simply by excessively delaying the availability of new drugs in the US.
Vaccines go through a different process in the US than most drugs, where the vaccine manufacturers self-certify the safety of their drugs and send a report to the FDA, who either signs off on the certification or doesn't. But the FDA doesn't manage any of the trials, unlike with other drugs. Vaccine manufacturers are also more protected from liability than other kinds of drug manufacturers, via the NVICP.
If a non-vaccine drug is approved first in the US, it's almost certainly because the drug is expensive to manufacture and the only country where the manufacturer can expect to break even (at least at first) is the US.
The effect this has on, for example, tv commercials, is amusing.
There are actual aired television commercials where the quickly spoken disclaimers include "death" as a side effect. I only notice this because I have subtitles enabled. They say it very fast.
That's the problem with a vaccine as compared to a therapeutic. You need to give it to a billion people for it to do any good. Some percentage of those people will have complications and die. If they fuck up with vaccine testing (which could cause the effect opposite of what the vaccine normally does, possibly weeks or _months_ after immunization), _millions_ could die, eclipsing the loss of life from the virus itself.
Before someone attempts to read my mind: I, and everyone else in my family, am fully immunized, including some vaccines (e.g. BCG) not normally administered in the US. I also do the flu shot every year.
But I do understand the risks a rushed vaccine could pose, and so I won't be taking it until at least 6 months after the initial wave of vaccination, and a careful study of population-scale safety and efficacy.
I'm not sure people understand the scale that vaccines work at. Right now--because we are close to wiping out polio--more people die every year from the polio vaccine than the actual disease. When you give billions of people a vaccine, even a one-in-a-million problem will still lead to thousands of deaths. It could be very hard to have wide-scale vaccines if we allowed people to sue for every death.
(Just to be clear: I am very pro-vax. Get all recommended vaccinations.)
How many people are actually dying from Polio vaccine? Which kind?
There are two kinds of Polio vaccine in widespread use. OPV is more effective but involves an attenuated (thus, "live") polio virus in the vaccine itself, you are in effect being deliberately infected with a version of the virus that should be helpless long enough for your immune system to figure out what it is and wipe it out. Because it actually is the live virus and eventually attenuation will wear off if the virus isn't destroyed, it can "leak" working copies of the virus into a population. If everybody in that population was immunised that hardly matters, but if so why are you still vaccinating...
The injectable vaccine used in many developed countries is both less effective and more expensive, but it's "dead", so can't result in anybody getting Polio. Since developed countries do not have endemic Polio it makes sense to just bite the budgetary bullet and use a less effective and more expensive vaccine.
The killed vaccine will only be causing side effects that you'd get from injecting almost anything. Side effects like anaphylaxis - similar to if a person with a severe nut allergy ate a nut. That's a "serious but rare" one-in-a-million type problem, but in the developed world the people who administer vaccines all know about anaphylaxis and will "just" fix it like my friend with a nut allergy would if he's given food with nuts in it by mistake. It's not fun but death should be extremely rare even for that one-in-a-million if prompt intervention occurs.
A more common side effect is syncope. Especially in teenage girls, some fraction of them will faint. It doesn't really matter what's in the shot, they just do. It's often psychosomatic, so it's important other patients don't see it happen (e.g. use a curtain) or it'll spread. Alone and unsupervised syncope could be fatal (you fall down, maybe smack your head on something), but that's extremely rare when supervised, you're usually sat down to get a shot, so you should just sort of slump over and get put into recovery by the person administering the shots.
Some vaccines are associated with GBS but it's fuzzy, the numbers are all over the place - they might actually cause less GBS than not being vaccinated, given how mysterious GBS is that could even make sense, maybe getting and fighting off diseases triggers the syndrome more often than the vaccination does.
> Thus, in areas with poor sanitation and low vaccination coverage, the spontaneous reversal of the vaccine[OPV]-derived virus to a virulent form and its spreading in the environment can lead to unvaccinated people becoming infected. Clinical disease, including paralysis, caused by vaccine-derived poliovirus (VDPV) is indistinguishable from that caused by wild polioviruses.
Right, and if OPV is what they're focused on, the thing is: Nobody is attempting a live attenuated coronavirus vaccine. So the OPV reversion situation is completely irrelevant to this exemption.
The problem is with the oral Sabin vaccine, not with the injectable Salk vaccine. And the problem is not for the kid that got the injection, but for it has a live virus that escape and after a few infections it can become dangerous to an unvaccinated person.
Anyway, a few years ago they removed strain 2 from the oral Sabin vaccine that was the strain that usually cause the problems, and when a country has no cases for long enough they switch and use only the injectable Salk vaccine.
This doesn't surprise me at all. Consider that the US has a federal agency set up specifically to pay out vaccination harm claims, and intentionally sets a low bar for those payouts. The rationale is that getting lots and lots of people vaccinated is a public good, so it's best to reassure people that if something bad happens that seems to be even vaguely correlated with a vaccine they take, they'll be taken care of financially.
Certainly this particular vaccine situation is unique, but indemnifying AstraZeneca, especially after asking them to sell the vaccine at cost, doesn't seem unreasonable.
Keep in mind that they won't be marketing this vaccine at all. They agree to produce the vaccine at no profit.
"To back its claim to forgo profits from the $1.2 billion collaboration in the United States, Astra has even granted the government access to financial accounts related to the venture, according to Dobber."
With no profit at stake, I would bet they sell directly to the governments. I wonder if this means they can make no profit in any country... That would certainly be good news for the world at large but it's not clear to me from the text in the article.
> That would certainly be good news for the world at large
If they made it for the us "profit free", then sold the patent/manufacturing process to their international subsidiaries for $1, then the rest of the countries and AstraZeneca is benefiting at the expense of the united states. We'd be basically funding the r&d for the vaccine and giving it to AstraZeneca for free.
This seems inline with at least US practices. Most (many?) vaccines are covered by the National Vaccine Injury Compensation Program, which shields the manufacturer from liability for covered injuries.
"That raises a huge red flag in my mind over its safety."
In this particular case, AstraZeneca are not doing the research for a COVID-19 vaccine. They have struck an agreement with the University of Oxford to manufacture and distribute the university's COVID-19 vaccine (still under development).
> That raises a huge red flag in my mind over its safety.
The Childhood Immunization Act of 1986 indemnifies all vaccine makers in the United States and requires a $0.75 Federal Excise Tax per dose that the government uses to indemnify vaccine manufacturers. Also, any such lawsuits can only be filed in The US Court of Federal Claims, an administrative court. No features of common litigation like discovery, expert witnesses, etc.
I would usually be with you.
I feel this is an exception. For obvious reasons (it's urgent, it's important, it's more important than any of the usual medical interventions).
But also for other reasons.
Here's the thing: Once a covid vaccine becomes available I expect pretty much every expert on the topic to look at the data, to think about the safety and many of them will comment on it. If there are concerns about the safety of this vaccine then someone will tell us.
What I want to express is this: We will know plenty of things about how risky a vaccine will be. We will have to make decisions. Both as a society and as individuals. Those decisions won't be easy. But I'm not really concerned that we won't hear about the downsides of a potential vaccine.
You can't have it both ways. It either comes fast and cheap or it takes much longer, it's safer and much more expensive.
Obviously here some countries will choose the former at least for the early coronavirus vaccines. This could create a useful middle-ground where the most vulnerable groups are vaccinated early and the rest of the population waits for post-release data.
the virus is killing tens of thousands a day. You want a vaccine as fast as possible? This is it. BUT...
Take it or leave. The, say $2 Billion in, profits that AstraZeneca can make from the vaccine don't justify being sued by 3 billion people for every headache or miscarriage. Or for real problems it may cause. By the way, in USA vaccine suits are settled by a special fund https://www.hrsa.gov/vaccine-compensation/index.html otherwise no one would make them.
If that sounded like red flag, Indian Government had given a specific date - August 15(this year) for the launch of their vaccine from a private company, by which the labs conducting trials for their vaccine should finish all three phases of vaccine trials and give approval[0]. When did the enrollment of participants for the trial start? July 7th(this year).
Why August 15? It is independence day and PM would like to make an announcement that India created the worlds first vaccine.
I don't think the issue is that simple. For example, a Lyme disease vaccine was pulled from the market over dubious safety issues [1]:
> This panel, described by one participant as raucous and riotous [35], provided a forum for all of the stakeholders [36]. In support of the vaccine, the FDA summarized the VAERS data and concluded that the evidence did not support a causative association. The vaccine manufacturer, now GlaxoSmithKline following a corporate merger, assured the assembled parties that the LYMErix™ vaccine did not cause harm to its recipients. They reviewed the status of their phase IV post-marketing surveillance. Practising physicians spoke of vaccine efficacy by describing the dramatic reduction in Lyme disease cases in their own practices.
> Others raised concerns about the vaccine's safety. Scientists argued a potential role for genetic susceptibility and OspA-related autoimmunity in vaccine complications. Poignant presentations by several ‘vaccine victims’ described in detail their suffering. The prosecuting lawyers for the largest class action suit claimed that manufacturers suppressed reports of adverse events from the licensing trial and provided inadequate warnings to genetically susceptible individuals.
> After hearing compelling testimonies from all the interested parties, the panel concluded the benefits of LYMErix™ continued to outweigh its risks. The panel made no changes to the product's labelling or indications. However, the FDA required the manufacturer to provide more vaccine safety and efficacy data by increasing the enrolment in their ongoing phase IV trial. The LYMErix™ vaccine remained available for public use.
> Market withdrawal
> Spawned by the press coverage of vaccine risks and the ongoing litigation, vaccine sales fell off dramatically in 2001. On 26 February 2002 GlaxoSmithKline decided to withdraw LYMErix™ from the market citing poor market performance [37].
> On 9 July 2003 the pharmaceutical giant settled the class action suits with Sheller, Ludwig & Bailey as well as several other smaller law firms. The final agreement included over 1 million dollars in legal fees for the prosecuting lawyers, but provided no financial compensation to the ‘vaccine victims’. The plaintiffs’ attorneys stated that the voluntary removal of LYMErix™ from the market accomplished the main goal of the suit. Despite the settlement, the manufacturer continued to deny that LYMErix™ caused harm and indicated that the decision to settle represented a choice based on economic concerns (i.e. the desire to avoid the costs of lengthy litigation) for a product showing relatively poor performance in the market.
Chemo is given to you after you have a super deadly disease, cancer. Unless you take chemo you are dead in a very short time so you very little to lose and a lot to gain . https://en.wikipedia.org/wiki/Hail_Mary_pass
Not every comment in a discussion needs to be nor is intended as a direct refutation. Sometimes people add additional relevant comments for consideration.
In this case, a treatment that is going to be given to 10-100K times as many people, most of whom are not suffering from an acute, life-threatening condition at the time of treatment, has a much different threshold for weighing the risks of possible harm.
A cancer treatment which cured 999 of 1000 patients and killed the 1000th outright would be a major breakthrough. A flu vaccine that did the same would rightly be rejected.
All vaccines in the USA have exempted by liability protections since 1986.
They are also exempt from all double blind placebo testing by the FDA because they have carved out a special exemption. Vaccines are classified as “biologics” which is a relic from the cold war era.
If someone gets vaccine damaged they have to go through a special vaccine court, which to this day has paid out $4.5 billion. Getting an award requires the awardee signing an NDA as a requirement.
Big pharmaceutical companies have a history of marketing drugs that aren't quite as good or harmless as they are made out to be.