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posted by martyb on Saturday May 02 2020, @09:12PM   Printer-friendly
from the festina-lente dept.

With a major pandemic sweeping the world, the standard process of clinical trials for drug approval has come under criticism as a needless source of bureaucracy and delay. Drug discovery chemist Derek Lowe in a blog post explains how clinical trials for drug approval work and the reasons behind the various requirements that the FDA and equivalent organisations around the world generally put in place before approving a new drug. He explains how most of these apparently pointless bureaucratic hurdles are actually there to help protect the integrity of the scientific process and ensure that the human subjects undergoing the trials are treated ethically. While a case can be made for relaxing some of these safeguards, especially in this time of pandemic, it is probably not a good idea to do so without at least understanding what these safeguards are for.

Determining how much of a pharmaceutical is needed to prepare for the trial. Ensuring your are actually preparing just that drug and not a polymorph. Proper laboratory and manufacturing practices to ensure the desired drug is actually prepared without impurities and contaminants. Preparing a plan for a drug trial. Demographics — age, gender, weight, current medications being taken. Getting a representative distribution of these as participants. And there's much more.


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  • (Score: 5, Insightful) by JoeMerchant on Saturday May 02 2020, @10:35PM (22 children)

    by JoeMerchant (3937) on Saturday May 02 2020, @10:35PM (#989617)

    There are some very good scientific/biological/statistical reasons why clinical trials are complicated, expensive, and long drawn out processes... however, there are also some straight up barrier to entry reasons behind it too. The "Big Pharma" can handle the cost and complexity, and smaller players can't; Big Pharma likes it that way and has goosed the scales a bit to keep their exclusive club as small as possible - after all: competition is bad for profits.

    Double-blind (where appropriate) multi-stage (to reduce risks to study subjects) multi-population (because 140lb white women from Boston are NOT the same as 240lb Hawaiian men) are all important to ensure that we really know what a drug is going to do before "testing" it on hundreds of millions of people.

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  • (Score: -1, Troll) by Anonymous Coward on Saturday May 02 2020, @11:15PM (10 children)

    by Anonymous Coward on Saturday May 02 2020, @11:15PM (#989630)

    Rubbish! Give it all of them and let herd immunity sort it out. That's the invisible hand taking your rectal temperature with its penis if you didn't notice.

    • (Score: 2, Interesting) by anubi on Sunday May 03 2020, @01:11AM (9 children)

      by anubi (2828) on Sunday May 03 2020, @01:11AM (#989656) Journal

      You have a crude way of saying it, but invariably, herd immunity or tolerance will be the final outcome.

      If it didn't, leprosy would have eventually wiped out the whole human race. Or that Covid19 would have completely wiped out those Chinese bats who supposedly gave it to us.

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      "Prove all things; hold fast that which is good." [KJV: I Thessalonians 5:21]
      • (Score: 2, Informative) by Anonymous Coward on Sunday May 03 2020, @03:18AM

        by Anonymous Coward on Sunday May 03 2020, @03:18AM (#989687)

        leprosy takes 20+ years to start presenting symptoms. and it is relatively hard to get in the first place. it has never reached epidemic status, even though it is still endemic in some regions.

      • (Score: 3, Insightful) by JoeMerchant on Sunday May 03 2020, @04:07AM (7 children)

        by JoeMerchant (3937) on Sunday May 03 2020, @04:07AM (#989694)

        Part of why it spreads so well is that a very large percentage of us already have immunity/tolerance - it's turning most of the people it infects into "Typhoid Marys."

        Latest numbers I've heard are 63,000 dead in the US, that's somewhere around 0.02% of the population, and I have a hard time believing that our present total infected level is less than 0.5%. In other words: I believe the overall death rate is pretty far below the 3.4% level that I've seen quoted. Which is fine, people wouldn't take it seriously if you told them the overall death rate after infection was 0.1%, and below age 70 was 0.01%, and the whole "curve flattening" thing wouldn't work.

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        • (Score: 1, Interesting) by Anonymous Coward on Sunday May 03 2020, @06:33AM (2 children)

          by Anonymous Coward on Sunday May 03 2020, @06:33AM (#989704)

          Viruses usually evolve to be less lethal due to the selective pressures on them. Last I checked, the various clades already have drastically differing mortality rates. They are also not distributed geographically in an even fashion, which is part of the reason why death rates are so different. It wouldn't be too surprising if those less-lethal strains are dragging the overall mortality rate down. Either way, the phylogenetic analysis will be interesting.

          • (Score: 2) by hendrikboom on Sunday May 03 2020, @04:07PM (1 child)

            by hendrikboom (1125) Subscriber Badge on Sunday May 03 2020, @04:07PM (#989823) Homepage Journal

            We can hope that immunity against the less-lethal strains confers immunity against the more lethal strains.

            • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @08:40PM

              by Anonymous Coward on Sunday May 03 2020, @08:40PM (#989894)

              It should. It is the major reason the Pandemic Flu disappeared.

        • (Score: 1, Informative) by Anonymous Coward on Sunday May 03 2020, @08:29AM (1 child)

          by Anonymous Coward on Sunday May 03 2020, @08:29AM (#989722)
          Which still translates to hundreds of thousands to millions of deaths if business is allowed to proceed as usual.
          • (Score: 2) by JoeMerchant on Sunday May 03 2020, @12:37PM

            by JoeMerchant (3937) on Sunday May 03 2020, @12:37PM (#989767)

            Which still translates to hundreds of thousands to millions of deaths if business is allowed to proceed as usual.

            Absolutely, and we should take measures to prevent that. Hell, we should also have taken stronger measures to prevent the million+ deaths caused by Gulf War II. It's just a shame that you have to lie to the general population to get them to react in an appropriate manner.

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        • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @11:46AM (1 child)

          by Anonymous Coward on Sunday May 03 2020, @11:46AM (#989753)

          whole "curve flattening" thing wouldn't work.

          Seems to work here in Germany.

          • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @02:36PM

            by Anonymous Coward on Sunday May 03 2020, @02:36PM (#989807)

            We know that Germany is reporting the underlying condition as the cause of death even if a person is infected, and that in the US we are reporting covid as the cause of death even if the person has an underlying condition. I spent some time yesterday trying to figure out Canada's death criteria but couldn't find it. Anyway, the point is, all these numbers being thrown around are just numbers and may not be all that comparable and whether Germany has or has not flattened the curve is hard to know.

  • (Score: 5, Insightful) by stormwyrm on Sunday May 03 2020, @02:44AM (6 children)

    by stormwyrm (717) on Sunday May 03 2020, @02:44AM (#989680) Journal
    All these regulations, procedures, and safeguards exist because a lot of missteps have happened along the way. Thanks to Josef Mengele and his ilk we've learned not to take human experimentation lightly. In 1937 we had a drug called elixir sulfanilamide enter the market, but it turned out to be lethally toxic, and it killed over a hundred people. Between that incident and the thalidomide scandal of the 1960s we've learned the necessity of requiring good scientific evidence of safety and efficacy. It is a given that barriers to entry are created by the regulations imposed to avoid similar things happening in the future, but I doubt that any but the most hardcore of libertarians would argue that such barriers are a bad thing, when the alternative is more lethally toxic drugs and horrifying experiments which don't even produce good science (much of the human experimentation conducted by the Nazis and the equally horrendous research of Unit 731 turned out to be scientifically worthless in the end).
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    • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @03:20AM (3 children)

      by Anonymous Coward on Sunday May 03 2020, @03:20AM (#989689)

      be careful.

      much of how we treat and know about hypothermia is from Mengele.

      • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @09:58AM (2 children)

        by Anonymous Coward on Sunday May 03 2020, @09:58AM (#989735)
        That we might have got some useful science out of such unethical experiments still doesn't justify what they did. There is considerable controversy as to just how scientifically useful the results of these hypothermia experiments conducted by the Nazis really are, even setting aside their horrendous disregard for ethics. A review article [nejm.org] in the New England Journal of Medicine makes the case that there is actually scant useful science to be gleaned from the hypothermia experiments in any case, concluding: "On analysis, the Dachau hypothermia study has all the ingredients of a scientific fraud, and rejection of the data on purely scientific grounds is inevitable. They cannot advance science or save human lives." The other Nazi human experiments, such as the twin studies that were personally conducted by Mengele himself, are even more scientifically worthless.
        • (Score: 2) by driverless on Sunday May 03 2020, @12:34PM (1 child)

          by driverless (4770) on Sunday May 03 2020, @12:34PM (#989765)

          I don't think we'll ever really find out whether those studies were useful or not: Can you see the NEJM publishing a paper "Nazi Medical Research Was Actually Quite Useful In Some Cases"? Certainly after the war the Allies scrambled to get their hands on the Nazi study data, and former Unit 731 members were snapped up by the US, so there was obviously some use for it. "Totally unethical but now it's been done, may as well use it".

          • (Score: 0) by Anonymous Coward on Sunday May 03 2020, @02:29PM

            by Anonymous Coward on Sunday May 03 2020, @02:29PM (#989805)
            There are some medical ethicists (tellingly, some of them are even Jewish) who argue exactly that: if the data exists and can be used to save lives, then it would be unethical not to use it, despite its provenance. The thing is, much of the data that does exist and is available for public consumption is actually garbage. Do try to read the paper I cited by Dr. Berger. He makes little reference to the ethics of what Hauptsturmführer Sigmund Rascher had done in his hypothermia experiments at Dachau, and studies only the experimental data that is publicly available. He concludes that the data is disorganised, inconsistent, incomplete, and makes conclusions that are unsupported by the data that are available. Rascher was also a liar and a crook who among other misdeeds actually kidnapped babies and passed them off as his own (his wife was in her late forties and likely no longer able to bear children); for these and other crimes he was executed at Dachau just three days before the camp was liberated by the Allies.
    • (Score: 2) by JoeMerchant on Sunday May 03 2020, @03:46AM

      by JoeMerchant (3937) on Sunday May 03 2020, @03:46AM (#989692)

      Barriers are good, and the scientific barriers should be higher than they are (or, alternately, an increased level of transparency on the already established scientific standards). What's not so good is that some of the barriers are costlier than they have to be to get the good science. Want to setup a new animal research lab? The requirements are beyond gratuitous, they're basically saying: "if you don't already have one, you're not going to get one."

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    • (Score: 2) by The Vocal Minority on Sunday May 03 2020, @05:17AM

      by The Vocal Minority (2765) on Sunday May 03 2020, @05:17AM (#989700) Journal

      Article was a good read - thanks for submitting this one.

  • (Score: 2) by driverless on Sunday May 03 2020, @08:01AM (3 children)

    by driverless (4770) on Sunday May 03 2020, @08:01AM (#989718)

    It's not just the obvious "hurr durr big pharma bad" that the previous thread degenerated into, there are so many things you need to control for that the tests end up being incredibly complicated and expensive. In particular as we've become aware of more and more things that can confound trials we've needed to add more and more mechanisms to deal with them. Look at what happens when you don't do it. As a well-known example, a certain Dr.Raoult in France, who doesn't believe in evolution, climate change, ..., and most importantly evidence-based medicine and who resigned from the editorial boards of several ASM journals after he was caught fudging experimental results in a journal paper, runs a... well, he called it a "trial" but one that met none of the requirements for a randomized controlled trial (RCT) - it's not just that he missed one of the requirements, he missed all of them - and the outcome was chaos. This is why there are stringent requirements for clinical trials, and why they tend to be really complex and expensive.

    • (Score: 2) by JoeMerchant on Sunday May 03 2020, @12:49PM (2 children)

      by JoeMerchant (3937) on Sunday May 03 2020, @12:49PM (#989769)

      In my opinion, the cure for most of these problems is transparency. When you get a "trial" run by another Raoult (and they are legion), with sufficient transparency in the process it can be called out for what it is, not only by competitors but also by watchdogs.

      People complain that automation is taking away all of their jobs - I think there's a huge industry waiting to be born in "industrial monitoring" - just because it only takes 100 people to run an industry that supplies all the corn for a continent doesn't mean those 100 people are doing their jobs in a way that meets the needs, or wants, of the corn customers. I'm not saying the 10,000 people employed by the proposed continental corn monitoring congress should tell the corn producers how to do their jobs - not exactly - but they should be telling the customers / consumers how the job is being done and provide them with the option to source their corn from preferred suppliers. A billion corn consumers can easily afford the $1 per year it would take to pay 10,000 people $100K per year to diligently monitor and report on the corn manufacturing and supply channels, and each other. Same thing could/should be applied to pharma, energy, foods in general, etc.

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      • (Score: 2) by driverless on Sunday May 03 2020, @12:53PM (1 child)

        by driverless (4770) on Sunday May 03 2020, @12:53PM (#989770)

        A billion corn consumers can easily afford the $1 per year it would take to pay 10,000 people $100K per year to diligently monitor and report on the corn manufacturing and supply channels, and each other. Same thing could/should be applied to pharma, energy, foods in general, etc.

        In theory we're already doing this, it's called "taxes" and "government regulators", problem is that many of them have been captured by the industries they're supposed to be watching. It does work in some areas, e.g. water quality monitoring, and in some countries which take it seriously. Problem is that in the US too much government oversight is communism or socialism or something and so you can't have it.

        • (Score: 2) by JoeMerchant on Sunday May 03 2020, @01:32PM

          by JoeMerchant (3937) on Sunday May 03 2020, @01:32PM (#989781)

          In the med device industry, regulation is effectively forcing the companies to do it to themselves - what's lacking is transparency to the consumer level. The device companies employ legions of compliance officers who ensure legally compliant levels of documentation and traceability discoverable by regulator (government, or agencies mandated to exist by EU regulation) audit. What I'm proposing is greater transparency / exposure of this kind of information to the end users of the products - and shifting the reporting structure such that the "transparency officers" don't report to the same CEO who is bonused on quarterly profits.

          As alluded to above, the EU regulators (ISO-9000 notified bodies and similar) are moving closer to this "monitoring by the people" model, but they still lack transparency to the consumers. Their scope of discovery is also tremendously restricted, the opposite of transparency. There's no reason that corporate internal financial details should be secret - following the money is often the most direct route to expose corruption.

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