Atlas sucked

[Aimless]

https://arstechnica.com/science/2017...vaccine-trial/

Will be interesting to see how the research community, universities and the industry respond.

[Lewkowski]

https://arstechnica.com/science/2017...vaccine-trial/

Will be interesting to see how the research community, universities and the industry respond.

"After testing out the vaccine on themselves for safety, they moved the trial to the Caribbean island."

They aren't being hypocritical about it at least.

Sounds like this specific case there are some issues but in general I highly approve of people looking for ways to get around burdensome regulation.

[Loki]

"Burdensome" = keeping people from unnecessary harm and making sure the results are accurate.

[Lewkowski]

"Burdensome" = keeping people from unnecessary harm and making sure the results are accurate.

I don't know all the specifics but the FDA is slow.

http://reason.com/archives/2014/03/2...ration-bullies

"Then the FDA grew, like a tumor. Today, it takes up to 15 years to get a new drug approved. Though most devices and drugs never are."

[LittleFuzzy]

I'm confused. To test a vaccine, a method of preventing infection with a virus via inoculation, they used people who are already infected and produce antibodies to the infection?

[Aimless]

I'm confused. To test a vaccine, a method of preventing infection with a virus via inoculation, they used people who are already infected and produce antibodies to the infection?

It was a Phase I study intended give an idea of safety and tolerability.

[Aimless]

I don't know all the specifics but the FDA is slow.

http://reason.com/archives/2014/03/2...ration-bullies

"Then the FDA grew, like a tumor. Today, it takes up to 15 years to get a new drug approved. Though most devices and drugs never are."

Extremely misleading. The approval process itself typically takes a year (very rough estimate). The 15 year figure is the time it takes to develop a drug from scratch. We now have higher standards for evidence.

[Loki]

Fake news. The evil scientists delight in keeping drugs from people who need them.

[Flixy]

Halford was quoted as saying: “Many of the virus vaccines we currently put in our kids—chickenpox, mumps, measles, and rubella—were developed using live-attenuated viruses in the ’50s, ’60s and ’70s when the regulatory landscape was more relaxed… and they have worked remarkably well.”

Yes, and in that period you had thalidomide as well. There's a reason regulation became stricter.

[Lewkowski]

Yes, and in that period you had thalidomide as well. There's a reason regulation became stricter.

Heh my article talks about that as well, incidentally FDA didn't determine jack about thalidomide.

"The FDA's first big success was stopping thalidomide, a drug that prevented the nausea of morning sickness. It was approved first in Europe, where some mothers who took it proceeded to give birth to children with no arms and legs.

The FDA didn't discover the problems with thalidomide. It was just slow. The drug application was stuck in the FDA's bureaucracy. But being slow prevented birth defects in America. It taught politicians and bureaucracy that slower is better."

[Flixy]

Yes and as Aimless already pointed out, the article isn't big on facts. AFAIK it was stalled because the FDA actually wanted to see clinical data rather than just talking the manufacturer's word.

[wiggin]

Lewk, I am giving you the benefit of the doubt on this one because I assume you do not have first hand knowledge of how drugs and devices are developed and regulated. So instead I'll educate you.

Making a new drug or device is indeed a typically slow process. For drugs, you first need to identify a worthwhile target (which itself might take decades of basic science research). Once you have a target but don't actually have a way of hitting said target, we typically start the 'clock' on drug development. Scientists have a variety of methods of developing drugs that appropriately modulate the targeted cellular process, but typically it involves very large scale screens against libraries of compounds (think hundreds of thousands) followed by sophisticated chemical modification of the best candidates to improve their safety and efficacy profiles. So let's say you've been very fortunate and it only took you 3 or 4 years to find a drug candidate that you think - based on cell studies and maybe some small animal studies - that it might do what you want it to do. Then you need to check a lot of boxes - can you manufacture the compound? How will it be delivered? Does it need a special formulation (excipients, etc.)? Once you have something in a form similar to what you'd want to use in a human - again, if you're lucky, you're maybe 5 years into your development process - only then do regulatory agencies really get involved.

Generally there is a relatively small and fairly straightforward set of tests that must be done before a regulatory agency will be comfortable starting a first in human trial - some basic toxicity/etc. tests on cells and small animals, and they might also want to see some sort of efficacy data in a good animal model. Essentially, they want some level of assurance that you aren't likely to kill your patients and that your therapy will, in the future, have some potential upside for the patient population. These tests can be done quite quickly - on the order of months - and are by and large tests you would want to do before putting it in a human anyways. Efficacy testing in animals might take a lot longer, depending on the indication they're going for, but that's a function of biological reality, not FDA bureaucracy.

Okay, so you've spent a few extra months (and maybe a million bucks) to check your boxes, and you go for a phase I trial. Phase I trials are intended to be very small numbers of patients testing the drug (or device) for safety/toxicity alone, with little to no consideration of efficacy in treating an indication. Depending on the technology in question, patients may even be healthy or otherwise not likely to benefit from the drug. It's really just to determine a safe dosing range and as a sanity check against any unforeseen consequences. Phase I trials, thus, tend to have short endpoints and relatively modest recruitment time and cost. Depending on the indication they might be completed in a year or much less. Again, this is something you'd probably want to do at any rate.

Then you typically carry out phase II and phase III trials - both of which look at efficacy in addition to safety, but with different scales. Phase II trials look at modestly larger numbers of patients, so while they're interested in following efficacy, it's also a way to see if any safety issues crop up that weren't seen in the very small Phase I setting. Phase III trials are even larger and are intended to provide a definitive answer about efficacy and safety for an FDA submission. These trials are typically where the biggest cost comes in (after initial R&D/discovery work) and also take the most time. But again, for an ethical scientist who wanted to accurately determine if their technology was safe and effective for use, there isn't much you'd change about trial design with or without the FDA.

The only big delay happens after you finish your phase III trials. You have to put all of your data - from the earliest preclinical tox and validation studies all the way through to the final phase III trial - into a big application and send it to a regulatory agency like the FDA. They then need to look at all of your data, analyze it themselves, discuss risk/benefit tradeoffs, and arrive at a decision. Typically this process takes about a year. It's certainly possible to make this shorter (likely be increasing funding for the FDA) but it's really the only major delay/cost the FDA adds to the process. And during the review period, typically companies are working on gearing up commercialization strategy and manufacturing and the like, so it's not obvious that they'd be able to go to market immediately if the FDA, say, halved the review period.

Perhaps more telling is that the FDA is well aware that this is costly for companies to wait for review, so they provide a number of different fast track designations that allow for expedited applications and review. For example, if a device is considered 'substantially similar' to a previous device (i.e. it's essentially an iteration of a basic and proven design), you can apply for approval through the '510k' process that is much faster, cheaper, and easier in terms of what you need to show in terms of clinical safety and efficacy data. You can get humanitarian exemptions for fast track approval of treatments that don't have good alternatives. You can get orphan drug status for drugs targeting tiny patient populations, which effectively limit what kind of clinical testing you can do. Generics and biosimilars have shorter approval cycles. Etc.

There are lots of ways to speed the approval process, and the FDA actively participates in them. Typically they encourage device/drug firms to meet with them early and often through so-called 'presubmission meetings' to make sure that the preclinical and clinical research plan looks reasonable and will likely pass muster. Companies will often carry out clinical trials in other countries where it is cheaper to operate (though still operating under strict IRB and regulatory controls, of course) in order to lessen the cost of clinical trials. I even was talking to an executive at one massive pharma company who said that they leverage their global operations to reduce the amount of time between closing a clinical trial and submitting regulatory paperwork by having their regulatory experts work on the submission around the clock, handing the documents off to offices around the globe.

I have spent a lot of time recently immersed in the world of preclinical and clinical testing and the subsequent FDA approval process. While it's certainly laborious and mind-bogglingly expensive, I've been continually impressed with how fundamentally reasonable the FDA has been most of the time. If there's a standard assay for a specific outcome that isn't optimal for your technology because of a solid scientific reason, you can just explain your logic, present an alternative, and they'll typically accept it. If you have clinical data that's okay but not amazing, if it meets their predetermined criteria for success, they'll often err on the side of approval in balancing risks and benefits to patients. And if you have an entirely new class of therapy that they're unfamiliar with, they'll work closely with you to assure that you can adequately demonstrate the safety and efficacy of your technology without an undue burden.

Working in a highly regulated industry is no fun, obviously. And there are times when you are frustrated by the bureaucracy or risk aversion involved (though one consolation is that you often get to insulate your technology a bit from competition because of the barrier to market entry). But by and large they're doing something we would want to do anyways in order to provide the best care for patients, and they're doing it in a broadly reasonable, fair, and sophisticated manner. It's not hard to get approval from someone (doesn't need to be the FDA) to test our a new drug (or vaccine) for a phase I trial - you really need to show pretty basic data. The 'scientists' who decided to do this trial without even an IRB were simply being lazy, unethical, and were probably bad at the science part to boot.

It has gotten harder to get approval for therapies, that is true. Partly that's because learning from past failures gives us better and more numerous tests to eliminate problematic compounds. Partly it's because a lot of the low hanging fruit has already been plucked - it's a lot harder to make a safe and effective drug to substantially improve on current clinical practice than it used to. Partly it's because new therapies tend to be so complex and so prone to unexpected challenges that it takes time to truly evaluate them. And part of it is that they were far too lax in the past, mostly because they didn't know any better. But I don't see a lot of evidence that it's just pointless bureaucracy holding back our champions of capitalism.

[Hazir]

Lewk, I am giving you the benefit of the doubt on this one because I assume you do not have first hand knowledge of how drugs and devices are developed and regulated. So instead I'll educate you.

Making a new drug or device is indeed a typically slow process. For drugs, you first need to identify a worthwhile target (which itself might take decades of basic science research). Once you have a target but don't actually have a way of hitting said target, we typically start the 'clock' on drug development. Scientists have a variety of methods of developing drugs that appropriately modulate the targeted cellular process, but typically it involves very large scale screens against libraries of compounds (think hundreds of thousands) followed by sophisticated chemical modification of the best candidates to improve their safety and efficacy profiles. So let's say you've been very fortunate and it only took you 3 or 4 years to find a drug candidate that you think - based on cell studies and maybe some small animal studies - that it might do what you want it to do. Then you need to check a lot of boxes - can you manufacture the compound? How will it be delivered? Does it need a special formulation (excipients, etc.)? Once you have something in a form similar to what you'd want to use in a human - again, if you're lucky, you're maybe 5 years into your development process - only then do regulatory agencies really get involved.

Generally there is a relatively small and fairly straightforward set of tests that must be done before a regulatory agency will be comfortable starting a first in human trial - some basic toxicity/etc. tests on cells and small animals, and they might also want to see some sort of efficacy data in a good animal model. Essentially, they want some level of assurance that you aren't likely to kill your patients and that your therapy will, in the future, have some potential upside for the patient population. These tests can be done quite quickly - on the order of months - and are by and large tests you would want to do before putting it in a human anyways. Efficacy testing in animals might take a lot longer, depending on the indication they're going for, but that's a function of biological reality, not FDA bureaucracy.

Okay, so you've spent a few extra months (and maybe a million bucks) to check your boxes, and you go for a phase I trial. Phase I trials are intended to be very small numbers of patients testing the drug (or device) for safety/toxicity alone, with little to no consideration of efficacy in treating an indication. Depending on the technology in question, patients may even be healthy or otherwise not likely to benefit from the drug. It's really just to determine a safe dosing range and as a sanity check against any unforeseen consequences. Phase I trials, thus, tend to have short endpoints and relatively modest recruitment time and cost. Depending on the indication they might be completed in a year or much less. Again, this is something you'd probably want to do at any rate.

Then you typically carry out phase II and phase III trials - both of which look at efficacy in addition to safety, but with different scales. Phase II trials look at modestly larger numbers of patients, so while they're interested in following efficacy, it's also a way to see if any safety issues crop up that weren't seen in the very small Phase I setting. Phase III trials are even larger and are intended to provide a definitive answer about efficacy and safety for an FDA submission. These trials are typically where the biggest cost comes in (after initial R&D/discovery work) and also take the most time. But again, for an ethical scientist who wanted to accurately determine if their technology was safe and effective for use, there isn't much you'd change about trial design with or without the FDA.

The only big delay happens after you finish your phase III trials. You have to put all of your data - from the earliest preclinical tox and validation studies all the way through to the final phase III trial - into a big application and send it to a regulatory agency like the FDA. They then need to look at all of your data, analyze it themselves, discuss risk/benefit tradeoffs, and arrive at a decision. Typically this process takes about a year. It's certainly possible to make this shorter (likely be increasing funding for the FDA) but it's really the only major delay/cost the FDA adds to the process. And during the review period, typically companies are working on gearing up commercialization strategy and manufacturing and the like, so it's not obvious that they'd be able to go to market immediately if the FDA, say, halved the review period.

Perhaps more telling is that the FDA is well aware that this is costly for companies to wait for review, so they provide a number of different fast track designations that allow for expedited applications and review. For example, if a device is considered 'substantially similar' to a previous device (i.e. it's essentially an iteration of a basic and proven design), you can apply for approval through the '510k' process that is much faster, cheaper, and easier in terms of what you need to show in terms of clinical safety and efficacy data. You can get humanitarian exemptions for fast track approval of treatments that don't have good alternatives. You can get orphan drug status for drugs targeting tiny patient populations, which effectively limit what kind of clinical testing you can do. Generics and biosimilars have shorter approval cycles. Etc.

There are lots of ways to speed the approval process, and the FDA actively participates in them. Typically they encourage device/drug firms to meet with them early and often through so-called 'presubmission meetings' to make sure that the preclinical and clinical research plan looks reasonable and will likely pass muster. Companies will often carry out clinical trials in other countries where it is cheaper to operate (though still operating under strict IRB and regulatory controls, of course) in order to lessen the cost of clinical trials. I even was talking to an executive at one massive pharma company who said that they leverage their global operations to reduce the amount of time between closing a clinical trial and submitting regulatory paperwork by having their regulatory experts work on the submission around the clock, handing the documents off to offices around the globe.

I have spent a lot of time recently immersed in the world of preclinical and clinical testing and the subsequent FDA approval process. While it's certainly laborious and mind-bogglingly expensive, I've been continually impressed with how fundamentally reasonable the FDA has been most of the time. If there's a standard assay for a specific outcome that isn't optimal for your technology because of a solid scientific reason, you can just explain your logic, present an alternative, and they'll typically accept it. If you have clinical data that's okay but not amazing, if it meets their predetermined criteria for success, they'll often err on the side of approval in balancing risks and benefits to patients. And if you have an entirely new class of therapy that they're unfamiliar with, they'll work closely with you to assure that you can adequately demonstrate the safety and efficacy of your technology without an undue burden.

Working in a highly regulated industry is no fun, obviously. And there are times when you are frustrated by the bureaucracy or risk aversion involved (though one consolation is that you often get to insulate your technology a bit from competition because of the barrier to market entry). But by and large they're doing something we would want to do anyways in order to provide the best care for patients, and they're doing it in a broadly reasonable, fair, and sophisticated manner. It's not hard to get approval from someone (doesn't need to be the FDA) to test our a new drug (or vaccine) for a phase I trial - you really need to show pretty basic data. The 'scientists' who decided to do this trial without even an IRB were simply being lazy, unethical, and were probably bad at the science part to boot.

It has gotten harder to get approval for therapies, that is true. Partly that's because learning from past failures gives us better and more numerous tests to eliminate problematic compounds. Partly it's because a lot of the low hanging fruit has already been plucked - it's a lot harder to make a safe and effective drug to substantially improve on current clinical practice than it used to. Partly it's because new therapies tend to be so complex and so prone to unexpected challenges that it takes time to truly evaluate them. And part of it is that they were far too lax in the past, mostly because they didn't know any better. But I don't see a lot of evidence that it's just pointless bureaucracy holding back our champions of capitalism.

And then you get politicians literally abusing that highly sensible system because they don't like the budgettary effects. It's remarkable how using anti-HiV medication in preventative ways is non-controversial in the US and huge chunks of the world where HIV is actually a health crisis, but not in Europe where identical application would cost around €700 a month per person.

[wiggin]

Is this an FDA/ce mark thing or a payer thing? Honestly I'm not really sure what you're referring to.

[Aimless]

And then you get politicians literally abusing that highly sensible system because they don't like the budgettary effects. It's remarkable how using anti-HiV medication in preventative ways is non-controversial in the US and huge chunks of the world where HIV is actually a health crisis, but not in Europe where identical application would cost around €700 a month per person.

They're coming around on pre-exposure prophylaxis. Bureaucrats and politicians approach health economics like bad accountants.

[Hazir]

They're coming around on pre-exposure prophylaxis. Bureaucrats and politicians approach health economics like bad accountants.

I know they are coming around, but it's gobsmacking how they hide behind questions of efficacy as if the data is completely inconclusive.

[LittleFuzzy]

And then you get politicians literally abusing that highly sensible system because they don't like the budgettary effects. It's remarkable how using anti-HiV medication in preventative ways is non-controversial in the US and huge chunks of the world where HIV is actually a health crisis, but not in Europe where identical application would cost around €700 a month per person.

It may be non-controversial but you'd still be paying less than I would (which is why I'm not on PrEP myself). Well, assuming I could get a prescription at all which I can't since I can't manage to find a new primary-care physician in the area willing to take on new patients.

[Aimless]

I know they are coming around, but it's gobsmacking how they hide behind questions of efficacy as if the data is completely inconclusive.

The simplistic answer is that it's easier to be deaf to/screw over smaller, stigmatized groups whose voices are weak. But there are also other cultural, organizational and psychological reasons for why so many bureaucrats take this particular approach to health-economic analysis, esp. in matters involving conditions that are not highly prevalent in the areas they administer. And even without that you have the question of opportunity cost in countries with socialized healthcare, which (I think?) is true of most of the EU. I don't find that line of reasoning, in the case of PrEP, to be compelling--but I can see where they're coming from.

Wrt using efficacy and health-economic data from other countries, obviously that information is not always directly transferable or applicable. For example, you may find yourself in a country where existing best treatment is so well-managed that a new treatment may have a lower advantage over that treatment compared to the situation in another country (classic example in Sweden involves old vs. newer direct-acting oral anticoagulants). As you say, data from other countries shouldn't be dismissed outright, but sometimes it takes more clinical experience before you cross the threshold that can trigger an affirmative decision.

Regardless, I'm glad that this specific matter has shifted out of the bureaucratic blind spot. peace

[Hazir]

It may be non-controversial but you'd still be paying less than I would (which is why I'm not on PrEP myself). Well, assuming I could get a prescription at all which I can't since I can't manage to find a new primary-care physician in the area willing to take on new patients.

I think I sent you a private message.

[Hazir]

The simplistic answer is that it's easier to be deaf to/screw over smaller, stigmatized groups whose voices are weak. But there are also other cultural, organizational and psychological reasons for why so many bureaucrats take this particular approach to health-economic analysis, esp. in matters involving conditions that are not highly prevalent in the areas they administer. And even without that you have the question of opportunity cost in countries with socialized healthcare, which (I think?) is true of most of the EU. I don't find that line of reasoning, in the case of PrEP, to be compelling--but I can see where they're coming from.

Wrt using efficacy and health-economic data from other countries, obviously that information is not always directly transferable or applicable. For example, you may find yourself in a country where existing best treatment is so well-managed that a new treatment may have a lower advantage over that treatment compared to the situation in another country (classic example in Sweden involves old vs. newer direct-acting oral anticoagulants). As you say, data from other countries shouldn't be dismissed outright, but sometimes it takes more clinical experience before you cross the threshold that can trigger an affirmative decision.

Regardless, I'm glad that this specific matter has shifted out of the bureaucratic blind spot. peace

For me it was a clear example where process is used against the interests of the involved parties.

[Aimless]

fo shizzle.

[Aimless]

https://arstechnica.com/science/2017...-took-it-away/

Extremely creepy.

[wiggin]

For me it was a clear example where process is used against the interests of the involved parties.

Hazir - I'm genuinely confused. Truvada already is approved by the EMA, right? So why can't someone just use it off-label for PrEP? Getting the label is more of a formality. My guess is that this is a payer problem.

[Lewkowski]

Lewk, I am giving you the benefit of the doubt on this one because I assume you do not have first hand knowledge of how drugs and devices are developed and regulated. So instead I'll educate you.

Making a new drug or device is indeed a typically slow process. For drugs, you first need to identify a worthwhile target (which itself might take decades of basic science research). Once you have a target but don't actually have a way of hitting said target, we typically start the 'clock' on drug development. Scientists have a variety of methods of developing drugs that appropriately modulate the targeted cellular process, but typically it involves very large scale screens against libraries of compounds (think hundreds of thousands) followed by sophisticated chemical modification of the best candidates to improve their safety and efficacy profiles. So let's say you've been very fortunate and it only took you 3 or 4 years to find a drug candidate that you think - based on cell studies and maybe some small animal studies - that it might do what you want it to do. Then you need to check a lot of boxes - can you manufacture the compound? How will it be delivered? Does it need a special formulation (excipients, etc.)? Once you have something in a form similar to what you'd want to use in a human - again, if you're lucky, you're maybe 5 years into your development process - only then do regulatory agencies really get involved.

Generally there is a relatively small and fairly straightforward set of tests that must be done before a regulatory agency will be comfortable starting a first in human trial - some basic toxicity/etc. tests on cells and small animals, and they might also want to see some sort of efficacy data in a good animal model. Essentially, they want some level of assurance that you aren't likely to kill your patients and that your therapy will, in the future, have some potential upside for the patient population. These tests can be done quite quickly - on the order of months - and are by and large tests you would want to do before putting it in a human anyways. Efficacy testing in animals might take a lot longer, depending on the indication they're going for, but that's a function of biological reality, not FDA bureaucracy.

Okay, so you've spent a few extra months (and maybe a million bucks) to check your boxes, and you go for a phase I trial. Phase I trials are intended to be very small numbers of patients testing the drug (or device) for safety/toxicity alone, with little to no consideration of efficacy in treating an indication. Depending on the technology in question, patients may even be healthy or otherwise not likely to benefit from the drug. It's really just to determine a safe dosing range and as a sanity check against any unforeseen consequences. Phase I trials, thus, tend to have short endpoints and relatively modest recruitment time and cost. Depending on the indication they might be completed in a year or much less. Again, this is something you'd probably want to do at any rate.

Then you typically carry out phase II and phase III trials - both of which look at efficacy in addition to safety, but with different scales. Phase II trials look at modestly larger numbers of patients, so while they're interested in following efficacy, it's also a way to see if any safety issues crop up that weren't seen in the very small Phase I setting. Phase III trials are even larger and are intended to provide a definitive answer about efficacy and safety for an FDA submission. These trials are typically where the biggest cost comes in (after initial R&D/discovery work) and also take the most time. But again, for an ethical scientist who wanted to accurately determine if their technology was safe and effective for use, there isn't much you'd change about trial design with or without the FDA.

The only big delay happens after you finish your phase III trials. You have to put all of your data - from the earliest preclinical tox and validation studies all the way through to the final phase III trial - into a big application and send it to a regulatory agency like the FDA. They then need to look at all of your data, analyze it themselves, discuss risk/benefit tradeoffs, and arrive at a decision. Typically this process takes about a year. It's certainly possible to make this shorter (likely be increasing funding for the FDA) but it's really the only major delay/cost the FDA adds to the process. And during the review period, typically companies are working on gearing up commercialization strategy and manufacturing and the like, so it's not obvious that they'd be able to go to market immediately if the FDA, say, halved the review period.

Perhaps more telling is that the FDA is well aware that this is costly for companies to wait for review, so they provide a number of different fast track designations that allow for expedited applications and review. For example, if a device is considered 'substantially similar' to a previous device (i.e. it's essentially an iteration of a basic and proven design), you can apply for approval through the '510k' process that is much faster, cheaper, and easier in terms of what you need to show in terms of clinical safety and efficacy data. You can get humanitarian exemptions for fast track approval of treatments that don't have good alternatives. You can get orphan drug status for drugs targeting tiny patient populations, which effectively limit what kind of clinical testing you can do. Generics and biosimilars have shorter approval cycles. Etc.

There are lots of ways to speed the approval process, and the FDA actively participates in them. Typically they encourage device/drug firms to meet with them early and often through so-called 'presubmission meetings' to make sure that the preclinical and clinical research plan looks reasonable and will likely pass muster. Companies will often carry out clinical trials in other countries where it is cheaper to operate (though still operating under strict IRB and regulatory controls, of course) in order to lessen the cost of clinical trials. I even was talking to an executive at one massive pharma company who said that they leverage their global operations to reduce the amount of time between closing a clinical trial and submitting regulatory paperwork by having their regulatory experts work on the submission around the clock, handing the documents off to offices around the globe.

I have spent a lot of time recently immersed in the world of preclinical and clinical testing and the subsequent FDA approval process. While it's certainly laborious and mind-bogglingly expensive, I've been continually impressed with how fundamentally reasonable the FDA has been most of the time. If there's a standard assay for a specific outcome that isn't optimal for your technology because of a solid scientific reason, you can just explain your logic, present an alternative, and they'll typically accept it. If you have clinical data that's okay but not amazing, if it meets their predetermined criteria for success, they'll often err on the side of approval in balancing risks and benefits to patients. And if you have an entirely new class of therapy that they're unfamiliar with, they'll work closely with you to assure that you can adequately demonstrate the safety and efficacy of your technology without an undue burden.

Working in a highly regulated industry is no fun, obviously. And there are times when you are frustrated by the bureaucracy or risk aversion involved (though one consolation is that you often get to insulate your technology a bit from competition because of the barrier to market entry). But by and large they're doing something we would want to do anyways in order to provide the best care for patients, and they're doing it in a broadly reasonable, fair, and sophisticated manner. It's not hard to get approval from someone (doesn't need to be the FDA) to test our a new drug (or vaccine) for a phase I trial - you really need to show pretty basic data. The 'scientists' who decided to do this trial without even an IRB were simply being lazy, unethical, and were probably bad at the science part to boot.

It has gotten harder to get approval for therapies, that is true. Partly that's because learning from past failures gives us better and more numerous tests to eliminate problematic compounds. Partly it's because a lot of the low hanging fruit has already been plucked - it's a lot harder to make a safe and effective drug to substantially improve on current clinical practice than it used to. Partly it's because new therapies tend to be so complex and so prone to unexpected challenges that it takes time to truly evaluate them. And part of it is that they were far too lax in the past, mostly because they didn't know any better. But I don't see a lot of evidence that it's just pointless bureaucracy holding back our champions of capitalism.

That was very informative, thank you. That being said I'm inherently wary of regulatory bodies. The FDA has every incentive to err on the side of extreme caution and little incentive to take a balanced approach of # of lives at risk vs. # of lives saved. If a new drug saves 10,000 people a year over existing medication and there is a one year delay that's cost 10,000 people their lives.

[Loki]

There are processes for expediting clinical trials when the drugs are shown to be extremely effective.

[Hazir]

Hazir - I'm genuinely confused. Truvada already is approved by the EMA, right? So why can't someone just use it off-label for PrEP? Getting the label is more of a formality. My guess is that this is a payer problem.

I am 100% convinced it is a payer issue, but that's about the last thing they want to admit.

[Loki]

A real impediment to research: the Institutional Review Board.

http://slatestarcodex.com/2017/08/29/my-irb-nightmare/

[Aimless]

As much as I enjoy this blog I sometimes can't shake the feeling that he's stretching the truth a little when describing his real life experiences. Nevertheless an entertaining description of a nightmare that, from my perspective working in a university hospital and a clinic where all but two doctors are actively working in clinical research, seems quite alien. My sympathies.

[Flixy]

A real impediment to research: the Institutional Review Board.

http://slatestarcodex.com/2017/08/29/my-irb-nightmare/

I only have experience with clinical trials that involve very real risks to patients, and then every question and demand the author whines about is reasonable. Seems to me like the IRB process is not very well equipped for trials like that (and that the author did next to no homework before starting).

On a side note the pencil thing is rather obvious as pencil can be erased. We're only allowed to use blue pens (to make copies more distinguishable from originals - colour copies apparently don't exist).

I can also echo Wiggin that in my (limited) experience the FDA is pretty cooperative and reasonably flexible. I just read tge FDA regulations that are directly applicable to my work (equipment and production) and those regulations are not crazy.

On a side note we're being audited for ISO 13485 in a couple of weeks, which will be the first time I am one of those being directly audited, wish me luck

[Loki]

The pencil point is a fair one, but accommodations should be made for reality. I've heard multiple horror stories about the lack of flexibility, which manifests itself most clearly when the IRB is dealing with fields it's not familiar with (like someone wanting to run a basic experiment in an African village). And instead of working with people to better understand the challenges, the IRB creates insurmountable obstacles that frequently make people give up.