[HN Gopher] Why are clinical trials so expensive? Tales from the...
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Why are clinical trials so expensive? Tales from the beast's belly
Author : wawayanda
Score : 156 points
Date : 2022-11-10 12:00 UTC (11 hours ago)
(HTM) web link (milkyeggs.com)
(TXT) w3m dump (milkyeggs.com)
| orzig wrote:
| This is incredibly important if you want to understand
| healthcare. Every little thing is expensive in a way that is hard
| to imagine before you get into the field.
| seidleroni wrote:
| As someone working at a company that has run several clinical
| trials, this really rings true, especially the segment on
| language translations.
| CharlieDigital wrote:
| I worked as Director of Engineering at a company for 10 years
| that built a SaaS for clinical trial document management.
|
| There is a weird perversion of incentives in the industry driven
| under the guise of "quality" and "safety" that from a software
| engineer's perspective, looked pretty bad to me because of how
| manual and error prone the process is.
|
| The problem is that the people who have the knowledge aren't
| incentived to make it more efficient or cost effective; the
| purpose of many of these folks is to simply extract rent from the
| system and blame regulations and "patient safety" concerns.
|
| At an MES startup, one of the industry stalwarts (starts with V)
| was more or less using mafia tactics to force the startup to use
| their software or they would voice no confidence with pharma
| companies where big V was already entrenched.
|
| One of my passion projects would be to build an open-core
| clinical trial document management system with a focus on
| automation and templatization of common processes and workflows.
| It's insane how much waste this system has.
| protomyth wrote:
| I worked on one in the 90's that was $50,000 a day for three
| years. The drug company, assuming the trial was successful, had
| about 4 years to make all its money back before the patent
| expired. Testing blood, urine, and stool for multiple things is
| expensive.
|
| Intellectually, I can understand the need for control groups, but
| I still think it's immoral. When you stare at a spreadsheet and
| see 70% of the control group is dead because some random number
| generator sorted them there like hell's own sorting hat, and the
| 98% of the people getting the drug are alive, you have no
| business talking about statistics. That graph will haunt me til
| my dying day.
| Slaminerag wrote:
| It's possible to stop a trial because the new drug is much more
| effective than the old drug. It's also possible to stop a trial
| because the new drug's significantly worse than the old. We've
| done both. Also, I hope that no one ever tells you that you
| have to do a drug schema change because "too many kids are
| dying."
| s1artibartfast wrote:
| You didn't kill 70% of the control group, you saved 98% of the
| experimental group.
|
| Also, with the appropriate trial design, you can stop the
| control and transfer patients once you see these big
| differences. Same thing should happen if you see the opposite,
| e.g. killing 70% of your experimental group.
| disgruntledphd2 wrote:
| Yeah if it's a potentially life saving treatment you really
| need that design that allows peeking at the results.
| protomyth wrote:
| Everyone knew the results of "standard treatment", that's why
| they were researching the drug. There were years and years of
| statistics.
|
| We killed 70% of the control group. Doomed by a random number
| generator.
| bigfudge wrote:
| If that was the case, the study actually was unethical.
|
| Some designs do include interim analyses and stopping
| rules.
|
| However in my view the real scandal is we are still using
| NHST for clinical trials. We should be continuously
| updating a sensible prior for the effect size and approving
| the drug/stopping the trial when we have sufficient
| evidence one way the other.
|
| As it is, the results of many underpowered trials are
| essentially thrown away because p > .05, which is stupid.
| This says nothing about the balance of evidence for the
| efficacy of an intervention... only the inertia and
| innumeracy of many clinicians preserves the tradition.
| s1artibartfast wrote:
| Not trying to invalidate your experience, but I think it is
| interesting and disagree.
|
| I suspect there are some people with different philosophies
| that that sit better with this sorta thing.
|
| It seems like you feel guilt not only for the harm you
| cause, but the harm you fail to prevent. Do you apply this
| logic to other parts of your life?
|
| How do you feel about the trolley problem, were you have to
| kill some to save others?
|
| How do you feel about the moral imperative of doctors to do
| no harm versus a utilitarian approach of maximize lives
| saved?
| protomyth wrote:
| I don't feel guilt, I still feel rage. I didn't determine
| any of the parameters or rules of the trial so I have no
| guilt on me. I just observed that the control group is
| dead because of some belief that they provided value when
| we already knew exactly what was going to happen to them.
|
| If you can prevent harm to others, then not doing so is
| just being an a$$. The trolley problem is just counting
| souls and really doesn't happen much in real life. The
| true problem is thinking the only choices are us/them
| versus everyone. I'm not a doctor so I have no idea how
| their ethics applies to their professional decisions.
| dekhn wrote:
| Control groups exist because they get us closer to global
| optimality.
|
| We can't eliminate suffering and dying of untreated
| people but it's generally considered ethical to eliminate
| suffering and dying of many while withholding that
| treatment from a subgroup of the study ("allowing them to
| die" by _not taking action_ , rather than the "causing
| them to die" by _taking action_ ).
|
| as long as that selection is done randomly and "fairly" I
| think it's an entirely acceptable risk. There have been
| trials that were truly badly run, and people died and
| suffered more than necessary, due to mistakes (often
| amateur ones) in the protocol. I'm more concerned about
| those types of deaths.
| s1artibartfast wrote:
| Thanks for clarifying your position
| funklute wrote:
| > Everyone knew
|
| If that was truly the case, then - as the parent hinted -
| it was the trial design that was the problem, and not the
| practice of having control groups.
|
| It is pretty common to stop trials early when it is obvious
| that the treatment works. Conversely, it is easy to think
| that "yea of course the new treatment works" despite the
| evidence not being there. The need for robust analysis must
| also be respected.
| protomyth wrote:
| It was my understanding that every study has a control
| group getting the standard care. I didn't see a study
| without such a control group.
| anthuswilliams wrote:
| No, in fact it is quite common to do "open label"
| clinical studies in which patients know what drug they
| are getting and no one is given the current standard of
| care. This is especially common in cancer, where the
| standard of care is so poor, and in rare diseases, where
| the patient population isn't large enough to admit such a
| comprehensive study.
|
| It is harder to have the same statistical confidence of
| efficacy and safety in such studies, but clinical
| researchers try to address those issues by varying e.g.
| dosage quantities, time in between doses, etc.
|
| Source: place I work is currently doing studies of this
| nature, and in general such studies seem to be well-
| understood and accepted by the FDA.
| s1artibartfast wrote:
| Randomization is independent from blinding. Open label
| studies can be either randomized or not, and controlled
| or not.
|
| The FDA will usually push for blinding if possible
| (sometimes it is not). They will also usually push for a
| randomization zed control with standard of care. They way
| the FDA views it (and I agree), is that control patients
| are not harmed because they are still getting the same
| care they would outside of the trial.
|
| It is usually unethical to have a treatment free arm.
| However, this has its own problem, where if you keep
| using equivalence comparisons, the end of the chain might
| not actually be any better
| funklute wrote:
| Yes, exactly. Control groups are incredibly important for
| ensuring good quality of clinical studies. It's a
| technique that solves multiple "calibration" problems,
| including:
|
| - being able to draw causal conclusions
|
| - being able to adjust against placebo effects
|
| A lot of clever people have tried to come up with ways of
| doing away with control groups. But ultimately, the best
| we can achieve is to stop early, as soon as the trial has
| a clear outcome. I do perhaps think this has become more
| common in recent times though, so perhaps the study you
| were involved in was at a time when early stopping wasn't
| really "the done thing".
|
| But it still beats "studies" done 100 years ago, when you
| might give someone a cough mixture, see that they
| improved (if they died, let's just ignore that), and
| conclude that it was the cough mixture that did it!
| robocat wrote:
| > the best we can achieve is to stop early, as soon as
| the trial has a clear outcome
|
| That must be really hard: if you wait for 95% confidence,
| you are selecting for 5% noise. If you repeatedly re-
| measure for 95% confidence, you strongly select for
| random noise.
|
| Not many medical advancements provide such an anomalously
| strong signal (98% survival versus 30% survival).
| funklute wrote:
| > If you repeatedly re-measure for 95% confidence, you
| strongly select for random noise.
|
| You can't use standard methods for early stopping - as
| you rightly point out, you get gibberish if you naively
| keep peeking at a growing data set. Instead, you have to
| use statistical methods that explicitly adjust for the
| repeated sampling in early stopping trials. This does
| make early stopping more complicated to analyse than a
| trial with a pre-determined duration.
| tsbischof wrote:
| For such a large effect it is quite possible to implement
| an adaptive trial design with unbalanced arms and interim
| analysis for efficacy. But you have to ask for this, the
| FDA will not necessarily suggest it directly.
| Khelavaster wrote:
| Peek-and-do-more is compatible with double-blindness, as long
| as the peeker-and-decider is different from the dispenser and
| patient.
| photochemsyn wrote:
| Interesting article, but the lack of mention of 'patent' or
| 'intellectual property' sort of stands out. There may be many
| out-of-patent drugs that are effective treatments for various
| conditions, but typically clinical trials for alternative uses of
| out-of-patent drugs are not pursued as anyone could then
| manufacture and sell them.
|
| This is not new - it dates back to the origins of the modern for-
| profit pharmaceutical industry, such as with Bayer's discovery of
| the anti-bacterial action of sulfanilimide (patented 1909) in the
| early 1930s (by which time patent had expired). Bayer made a
| derivative of sulfanilimide, i.e. Prontosil (patented in 1932)
| and tried to convince the world that this was the more effective
| product. In reality, it just broke down to sulfanilimide once
| ingested, that being the active species.
|
| As far as clinical trials in the USA, there have been numerous
| scandals regarding lack of consent, failure to halt trials
| immediately on indication of severe side effects, etc. Major
| stories about this came out in 2005, 2008, etc. Then there's the
| world of unregulated third-world clincal trial testing, and
| actual falsification of clinical trial data by contractors hired
| to run trials for various Big Pharma outfits, such as this from
| 2022.
|
| https://endpts.com/clinical-trial-coordinators-sentenced-to-...
|
| > "Tellus, which has worked with big-name pharma sponsors in the
| past like Pfizer, Gilead, Takeda, Boehringer Ingelheim and Eli
| Lilly, initially came under scrutiny for two trials related to
| opioid dependency, two for irritable bowel syndrome, and one for
| diabetes."
|
| That's just organized crime 101: hire a contractor to do the
| dirty work, keep your own hands clean, claim ignorance, act
| shocked, promise reforms, etc.
|
| Best solution I've heard of is a move to open-source (patent-
| free) drug discovery with federally financed clinical trials.
| Since almost all new drugs are discovered at universities with
| federal funds (see remdecivir, mRNA vaccines, etc.), before being
| exclusively licensed to private interests, the quickest way to
| that is to revoke Bayh-Dole and state that universities must non-
| exclusively license their discoveries to any parties for a flat
| fee.
| pfdietz wrote:
| One thing not mentioned: people are paid to participate in
| clinical trials. For example, in a vaccine clinical trial I know
| about, participants are paid over $1000 (in dribs and drabs over
| the course of the trial, as a retention mechanism.)
|
| With tens of thousands of participants, this cost adds up.
| idealmedtech wrote:
| Patient compensation is intentionally limited to prevent
| economic incentives from interfering with informed consent; pay
| people too much and they may participate in research that they
| would have passed on. Also, speaking from experience, patient
| compensation is a very small amount (5% or less) of overall
| cost. The vast majority goes to clinical staff costs, room
| costs, hospital overhead, labs etc.
| pfdietz wrote:
| That's not a vaccine trial though, right? I'm figuring those
| need more participants and have more retention problems, as
| well as less risk of informed consent problems.
| ebiester wrote:
| I mean, the CONFIRM trial
| (https://www.research.va.gov/currents/1117-Largest-ever-VA-
| cl...) had 50,000 patients. (That's not a pharmaceutical
| sponsor-led clinical trial, but it is a clinical trial.)
|
| But yes, the largest phase 3 trials ever are generally
| vaccines. https://www.evaluate.com/vantage/articles/news/sn
| ippets/its-...
| boole1854 wrote:
| > Patient compensation is intentionally limited to prevent
| economic incentives from interfering with informed consent;
| pay people too much and they may participate in research that
| they would have passed on.
|
| I'm not sure I understand the logic here. How does agreement
| suddenly become less informed or less consensual because the
| participant gets paid more? Sure, if they get paid more, they
| might be willing to accept more risk or do something more
| unpleasant. But that seems fair, not immoral. Why would it be
| more fair to say "yes, perhaps this trial is risky, but we
| only want participants who don't demand to be compensated
| much for the risk they take"? If anything, maybe _that_
| approach leads to less informed consent by filtering out the
| people who actually understand the risk and would have only
| agreed to participant in exchange for more compensation!
|
| Should we also be morally offended any time an employer
| raises wages in order to attract more workers?
| knodi123 wrote:
| > How does agreement suddenly become less informed or less
| consensual because the participant gets paid more
|
| Why shouldn't college professors sleep with their students?
| How does the relationship become less informed or less
| consensual? The answer is power.
|
| Money is power, and too large of a power imbalance corrupts
| a relationship. Money is pressure, and too much pressure is
| coercive.
| JamesianP wrote:
| Professors historically were prohibited from
| relationships with students because it creates the
| appearance (and high likelihood) of favoritism. And it
| probably pisses parents off a lot because the age
| difference seems creepy.
|
| "Power" is a relatively new argument. These days the
| student has the power to utterly destroy the professor.
| The professor has at best the charismatic "power"
| equivalent to any number of smooth pickup artists
| occupying college dorms, of getting a temporary good
| time.
| s1artibartfast wrote:
| I think it's still a fair question. The money is intended
| to be an incentive. If the trial is ethical and has a
| positive risk benefit ratio, there is no harm from
| coercion.
| knodi123 wrote:
| Okay, but what if a person sincerely does not want to
| participate in a medical trial? But then when he sees the
| dollar figure, he thinks "well, shit, I hate doing this,
| but I can't afford to turn that much money down."
|
| Same reason we don't allow the purchase of kidneys, and
| the same reason we think it's unethical for a millionaire
| with a tophat and a monocle to offer two homeless guys a
| wad of money to the winner if they fight each other.
| Sure, it's an adult making a decision of their own free
| will- but it's obviously unethical.
| pinky1417 wrote:
| That's true. Good Clinical Practice guidelines say that
| Institutional Review Boards must evaluate compensation is not
| too high otherwise it constitutes "undue influence".
|
| ...but I think that's a terrible idea. I understand that, to
| come up with a far-fetched example, high compensation could
| result in some weird edge cases where, for example, a Phase I
| trial with healthy volunteers and a non-preventive drug
| candidate (e.g. an antibiotic rather than a COVID vaccine),
| but you're confident that drug is going to kill 99% of the
| volunteers so you offer $10 million to each volunteer. A
| totally informed volunteer might view this as something akin
| to a life insurance policy that pays out to the family even
| upon suicide. I don't personally see an ethical problem with
| that so long as volunteers are _really_ well-informed, but I
| could see how others and the law would be uncomfortable with
| the ethics of such a situation.
|
| But aside from that far-fetched situation, it seems harmful
| to limit compensation... especially if it's true that patient
| compensation is a small part of overall cost. Perhaps if
| every trial doubled compensation to 10% of today's overall
| costs, absolute overall costs would _decrease_ because less
| effort has to go into patient recruitment.
|
| I do see one real-world issue with high compensation, but it
| has nothing to do with ethics. It has to do with statistical
| interpretation. If you start dangling too much money to
| participate in a trial, you may change the kind of people who
| participate in the trial. These individuals might not be
| representative of the actual users of the drug. The problem
| is similar to running a drug trial in the US versus Japan.
| The US has a pretty diverse population with respect to
| genetics. Japan, in contrast, is almost entirely ethnic
| Japanese. If you were to somehow succeed in using Japanese
| trial data to market an acne cream in the US, the same drug
| that cleared up Japanese faces might result in Venezuelans
| having their noses fall off!
|
| However, I'm cautiously optimistic that higher compensation
| could make trials _more_ representative. In my mind, I could
| see how African-Americans, who tend to participate in trials
| at a lower rate than their Caucasian fellow humans, would, if
| only for the shameful history of the Tuskegee Syphilis Study,
| require greater compensation to take the risk of
| participating in a trial.
| idealmedtech wrote:
| As you said, at the end of the day it's an ethical
| guideline that must be upheld, more than something based in
| economics. We do compensate participants as well as we're
| allowed within these guidelines!
|
| I agree with your points, but compensation must be approved
| by the independent institutional review board, who is
| accountable to national ethical review boards and thus acts
| very conservatively.
| JamesianP wrote:
| I would think the worst of such edge cases should be
| prohibited by law anyway. A set of more subjects is
| presumably a superset of a set with less subjects. So any
| issues can be addressed by screening them better. I suppose
| there could be a greater problem with fraud as people claim
| to have issues when they don't.
|
| It just seems unfair to subjects to me. Not to mention
| paternalistic. Every other actor in the process gets
| enriched based on (limitless it seems) market rates for
| their contribution, except for the subjects who take on all
| the risk.
| fuckyah wrote:
| robocat wrote:
| Call me cynical, but this could apply in most any industry:
| Suppose that one tries to push back on inefficiency in
| generalsomeone naive but well-intentioned, like myself, who is
| tired of the Long March of interminable meetings. In fact, I
| expressed my concerns about the proliferation of unproductive
| meetings in the clinical department to the C-suite executives
| (with whom I remain on good terms!) and, together, we carefully
| planned a series of reforms to company culture designed to reduce
| meeting burden. We hoped to implement a soft cap on the number of
| meeting participants and the length of a meeting, to normalize
| efficient behavior such as leaving meetings midway if you no
| longer need to participate in the remainder, starting meetings on
| time without 15 minutes of small talk, and a mandated review of
| all recurring meetings with the intention of pruning overall
| meeting load by >50%. Ironically, on the morning that
| we planned on roll out these reforms, we received urgent and
| vehement protests from a member of middle management who was
| notorious for obsessively overscheduling meetings with huge
| participant lists just for the sake of "inclusion" and
| "engagement." Because this particular manager was currently
| playing a crucial role in managing the rollout of several
| clinical trials at the same time, executive management judged
| that the risk of alienating him was too high, and to this day I
| believe these reforms remain unimplemented (although I hear he
| has since left the company, so perhaps my slides will eventually
| see the light of day).
| manv1 wrote:
| FYI, the RFP process is basically the same in other industries.
| apohn wrote:
| I came here to post the same thing.
|
| I used to be in enterprise software sales and consulting and
| have been involved for RFIs/RFPs across multiple industries. I
| don't know a single person who thought the process was sensible
| or efficient. Unless you have an person whose job is dedicated
| to responding to the questions, it's basically just a game of
| passing a hot coal around until you have something you can
| submit.
| NDizzle wrote:
| One point in there - data management. It varies in cost because
| on the upper end, that includes support for data change requests
| for the life of the trial. Zillions of people involved, human
| error, need paper trails and sign offs to fix most things.
| bmj wrote:
| This is usually downstream of the CROs, or, at least contracted
| out. What's most interesting to me about the post is that the
| author doesn't mention any efficiencies gained by moving to
| electronic data collection. But, I also understand why it isn't
| mentioned -- I work for an EDC/eCOA provider, and our biggest
| competitor for new business isn't our competitors in the space,
| it is paper-based data collection.
| olieidel wrote:
| This is so, so interesting. Thanks so much for posting this!
|
| The author already touched upon a few hypotheses why the industry
| has arrived at this state. There's one I'd like to highlight: The
| author, now having gone through this experience, would actually
| be in a perfect position to found their own CRO and implement all
| their efficiency learnings there. However, they probably look
| back upon this experience and think it was super painful and
| would prefer to do fun stuff like developing software instead.
|
| That, for me, is the main reason. There are smart, structured,
| pragmatic people who got acquainted with this industry, but they
| choose to leave it.
|
| And that's sad!
|
| So the solution would be to find a group of smart, structured,
| pragmatic people with a high tolerance for bureaucratic pain and
| give them the resources to make this industry more efficient.
|
| And here's my plug: That's exactly what we're doing at
| OpenRegulatory [1], albeit for medical device software and not
| for clinical trials. Among other things, we've published all our
| document templates for free (also on GitHub), host a free Slack
| community for companies to help each other out, and offer a
| compliance SaaS with transparent and fair pricing. It's still a
| long way, but it's a start :)
|
| [1] https://openregulatory.com
| BeefySwain wrote:
| Your company is very interesting. I briefly looked over the
| website, but couldn't tell what country(ies?) you operate in?
| My assumption is the regulatory requirements of each country
| are dramatically different, so seeing the pricing in not $
| makes me think it's unlikely you offer services in the US, for
| instance.
| jtwaleson wrote:
| They operate mostly in Germany, but the Slack community
| around it is broader, I think 90% is EU based though.
| refurb wrote:
| I worked in clinical development and the rough estimate of phase
| 3 clinical trial costs (this is a few years back) was $15,000 per
| patient per year.
|
| Depending on the trial design it can be less (less frequent
| follow up, less invasive testing) or a lot more (say doing
| multiple MRIs or other expensive imaging).
|
| It's kind of mind blowing when you think about the really big
| trials for medications like cholesterol. Trials are often 30,000
| or more patients, in two trials for 2-3 years.
|
| You're roughly talking about $2B or more just for phase 3
| (ignoring all the earlier trials and preclinical work).
| s1artibartfast wrote:
| Another huge cost is comparator products. Some trials budgets I
| have seen spent 100-200+ million purchasing the drugs they are
| trying to outperform. This is for trials with <1000 patients.
| idealmedtech wrote:
| There's a reason why we ended up putting our trials together
| essentially by trial and error! You learn a lot by writing your
| own clinical protocol, interacting with the FDA etc. It's an
| intimidating process at the outset, but if you can save $200k on
| a first-in-man study by not contracting a CRO, that's gonna
| extend your runway by a lot!
| seidleroni wrote:
| A fair point, but with the FDA responses taking up to 30 days
| you burn a lot of runway.
| ska wrote:
| They have a 180 day review commitment. A 30 day delay on
| their side would be unusual and burn a big chunk of that
| clock.
| s1artibartfast wrote:
| That's why you have several Type B or Type C meetings during
| development to work out the kinks before you submit a
| protocol.
| vibrio wrote:
| I don't completely disagree with your point, but for one's
| clinical regulatory strategy, perhaps "trial and error" isn't
| the best branding to appeal to investigators, patients,
| regulators or investors.
| idealmedtech wrote:
| Perhaps I was being too self deprecating! We worked closely
| with the FDA through multiple QSub meetings to make sure it
| was up to snuff, and did a lot of legwork on the backend to
| make sure we understood what they were asking for. 3 or 4
| revisions later, we had an approval!
| s1artibartfast wrote:
| Are you under the impression that that's how they branded
| things?
| adultSwim wrote:
| If you are worried about $200k, do you have enough money to
| bring your product to market?
| idealmedtech wrote:
| When we started putting the trial together, we were still
| self funded. In medical device, to get to series A you need
| human data, so by doing the trial protocol ourselves, we
| avoid the chicken and egg problem of needing money in order
| to raise money. Once you get human data, your valuation
| skyrockets.
| SubiculumCode wrote:
| Nicely written piece highlighting the value of in-house expertise
| and capabilities, providing a lesson that translates very well
| imo to why government projects should have more in house
| expertise and not contract everything to the private sector.
| napier wrote:
| Best explanation I've read online. Most attempts at describing
| why boil down to the circular "clinical trials are very expensive
| because the process of getting a new drug approved is lengthy,
| complex and expensive".
| Melissa_bime wrote:
| I totally understand the frustrations experienced by the author
| of this post. I am a nurse and my exposure to the Clinical Trial
| Industry came from a more bottoms up entry point. Its mind
| boggling to the the total costs CRO's charge for the services
| compared to the eventual experience for the staff and patients
| taking part in these studies. CRO's are in dire need of
| disruption. I also agree about the incestuous industry hence the
| very slow progress being observed. It's hard to show any progress
| when it's the same people moving around the same companies and
| implementing ideas that are somewhat outdated. Also, from a cost
| perspective, i think the future is also coming to a place where
| Clinical trials get outsourced outside the US. Sites and PI's
| outside the US should be empowered to run this clinical trials as
| they provide a more cost effective solution with regards to
| operational costs and also access to an ever growing number of
| patients, reducing clinical trials timelines that lead to
| increased costs. I understand the need for CRO's to maintain
| quality, and they can do this by building out the right
| relationships and partnerships with overseas contractors, but i
| believe in the long run, this is the solution. I believe this so
| much that i launched my own CRO company. Infiuss Health. The goal
| of this company is to unlock the potential for studies to the run
| by CROs and smaller life science companies outside the US. We are
| starting with Africa. As soon as we can unlock this population
| that has traditionally just been taboo to life science companies,
| imagine the lengths we could go with with access other
| geographies.
| invitrom wrote:
| I am eagerly waiting for the clinical trial on BC007 for Long
| Covid. As a chronically ill patient the slow pace of research is
| almost unbearable.
| mandmandam wrote:
| This all sounds so familiar.
|
| How many industries could these sentences descrive, stripped of
| context?
|
| Or more easily, are there _any_ industries where this is _not_
| the norm?
|
| > an industry which is severely lacking in human capital and
| fully captured by bureaucratic tendencies
|
| > going through this process is an extended exercise in sheer
| absurdity.
|
| > meaningless bloat
|
| > a farcical "data-driven" scoring process
|
| > there was an intermediary clinical organization we attempted to
| work with which was so obviously attempting to grift money from
| our coffers, the entire relationship escalated into the level of
| back-and-forth legal threats
|
| > One cannot help but get the impression that this is an industry
| which is, at best, severely lacking in anything that could be
| called "human capital" and, in reality, simply deeply unserious
|
| > despite the very large amount of boilerplate content that every
| single actor in this ecosystem has spent thousands of hours of
| manpower developing, there seem to have been very few actual
| gains made in simplifying common tasks or processes!
|
| ... Et cetera.
|
| To me, this sounds a lot like processes in education, teaching,
| energy, environmental protection, agriculture, research, arms,
| media, law, IT, etc.
|
| I don't believe we can afford to remain this stupid, however much
| money the inefficiencies are making for those at the top.
| knodi123 wrote:
| > Or more easily, are there any industries where this is not
| the norm?
|
| porn?
|
| Or in general, any business with highly mobile
| customers/employees and narrow profit margins.
| turnsout wrote:
| Great summary! And yet, for all their problems, CROs are
| sometimes still the fastest alternative. We did a clinical trial
| for a software platform a few years ago, and hoped to partner
| with a prestigious hospital system to run the trial.
|
| The hospital partner was 100% on board--our protocol just had to
| pass their internal review board (IRB). IRB is a black box, and
| they could only give us a vague estimate of how long this would
| take. We had a huge team, and every week we sat around waiting
| cost about $200k.
|
| Finally the client couldn't take the uncertainty and burn rate
| anymore, and they reached out to a CRO they had used in the past.
| The CRO's IRB had a fixed timeline (2 weeks?), and we were
| onboarding patients a short time later.
| MichaelZuo wrote:
| Why couldn't the team be tasked on something else while
| waiting?
| 1auralynn wrote:
| Yeah the lesson with getting IRB approval if you want it done
| in less than 6 months is to always use an external IRB (if
| possible). Institutional IRBs are sloooooowwww.
| BurningFrog wrote:
| Soap box: IRBs are one of many things deteriorating modern
| science, and in great need of reform.
| getsloped wrote:
| The logistical inefficiencies mentioned in this article are mind
| boggling when compared to what we've come to expect in different
| industries. We all know healthcare is always a little behind the
| curve, but with clinical trials, we're talking decades.
|
| For example: most clinical studies have no way to track samples
| going from sites to labs beyond a hope, prayer, and constellation
| of unconnected spreadsheets. The status quo is to write a 50 page
| lab manual and include a wall of text and bullets outlining a
| list of multiple stakeholders that need to be emailed a tracking
| number each time a sample is shipped. Not to mention there are
| days you really shouldn't ship samples. Labs have no idea when
| samples are going to show up. Seriously, samples just show up,
| they open the box expecting a piece of paper to identify the
| samples.
|
| An incredible amount of perfectly good, usable samples get LOST
| or DESTROYED due to the fact that there's no way to track any of
| these samples or coordinate stakeholders. We're talking critical
| samples, like blood from kids with cancer. It's absolutely
| ridiculous.
|
| Compare this sob story to the fact that I know in _realtime_
| where all the dumb shit I bought on Amazon is. The cognitive
| dissonance here is beyond comparison!
|
| + + +
|
| About 8 years ago my brother and I were given a window into this
| problem. Being Amazon FBA sellers ourselves, we thought, "hey now
| that can't be too hard to fix" and thus began the wild journey of
| Slope [0]. What we learned working on this problem is that
| clinical research sites literally get crapped on left and right
| with ridiculous contracts & protocols written by people who don't
| understand the clinical setting or logistics in general. With
| each research site running 30-50 clinical studies and each of
| those studies having its own catalog of kits, shippers, and other
| inventory, it's no wonder why clinical research is so expensive!
| And this is just supply chain folks.
|
| Slope started by making an inventory and sample management
| software to address the needs of sites and have worked backwards
| into selling this platform to Sponsors and CROs. While I have
| your attention, we're hiring a head of engineering now and will
| have a JD up for a product manager next week [1]. Thanks for
| reading!
|
| [0] https://www.slope.io/ [1] https://www.slope.io/jobs/head-of-
| engineering
| trap_goes_hot wrote:
| People complain about industries with bureaucracy but nobody
| wants to take the hit and actually work in those industries.
| They want magically for their pay/benefits/culture incentives
| to align.
| ativzzz wrote:
| Exactly - like the OP you replied to - Slope are trying to
| hire a Head of engineering for a salary that competent
| mid/senior level engineers should be easily getting. It's no
| tech industry, and the work is less fun
| xiphias2 wrote:
| While there are lots of new biotech tools, most of the illnesses
| left to treat are caused by aging, when the human system falls
| apart from the interaction of old parts, therefore super hard to
| treat.
|
| At this point I gave up waiting for a medical solution for my
| chronic illness, and have a better hope that I can live 15-20
| years with it and rejuvenate my body after that time period.
| wins32767 wrote:
| The author doesn't really understand the details of the
| operations of clinical trials, though this is a good overview of
| the kinds of outcomes that show up. I worked on operations
| software for clinical trials for about a decade, and there are
| (mostly necessary) regulatory drivers a large fraction of the
| complexity he complains about. The first order effects of the
| regulations are pretty straightforward, but when you get into
| second, third, and fourth order impacts, you start seeing some of
| the outcomes he's describing.
| [deleted]
| AlbertCory wrote:
| I have to admit I found this tl;dr. That's my bad, because it's
| an important article.
|
| All the bureaucratese in the RFPs and heavy-duty lawyering just
| add, unnecessarily and hugely, to the cost. At bottom, though,
| you have:
|
| 1) A lot of human beings who have to be recruited and paid to be
| subjects
|
| 2) Medical institutions that have to administer the drugs or run
| the devices
|
| 3) A sufficient amount of elapsed time for effects and side
| effects to manifest
|
| 4) A reporting system that's trustworthy
|
| So at best you could cut (puts finger to the wind) _half_ the
| cost? Surely not 90%.
| pinky1417 wrote:
| I worked at a small-to-mid-size clinical research organization
| for a hot minute. That company had its own set of - let's say
| "unique" - problems*, but the author touched on many of the
| issues I saw in my short experience at a CRO. I was in an odd
| (for me), pseudo-managerial, HR-type role at the company (a role
| in which I'll be the first to admit I wasn't good at) so perhaps
| I can offer some additional perspective.
|
| But first, I want to give some background on an important part of
| the CRO world: the "clinical research associate" or "CRA". CRAs
| are are the CRO's meat-and-potatoes, boots-on-the-ground, core,
| etc. after contracts have been signed. A CRA is the person who
| actually goes to clinical trial "sites" (e.g. a doctor's office,
| a hospital, or, even a dedicated facility for clinical trial
| participants). The CRA goes to each trial site, talks to the doc,
| makes sure participant recruitment is going well, checks/writes
| documentation, and follows up as the trial goes on. In other
| words, the performance of the CRAs strongly & directly affects
| the performance of the clinical trial.
|
| Anyway, my top issues with clinical trials today are:
|
| (1) Poor patient recruitment - this is a major problem. There is,
| of course, lots of variability between trials and CROs with
| respect to recruitment, but it should be telling that "trial
| rescue" is often done (at least where I worked) as a result of
| the incumbent CRO's inability to recruit enough patients.
|
| (2) (Related) Limiting pay to study participants: although it's
| up to the institutional review board's interpretation (IRB, an
| ostensibly independent entity that's supposed to sign off on the
| trial's ethics), good clinical practice (GCP) guidelines states
| that paying participants too much would be "undue influence". I
| have no idea how this plays out in practice, but I think it's a
| bad guideline. Most of the other parts of GCP are good things -
| stuff like informed consent and not coercing subjects - but this
| one is (again, in my opinion) probably raising trial costs
| through recruitment delays or total non-recruitment, even
| accounting for the extra cost of paying participants more.
|
| (3) Clinical Research Associate (CRA) training & hiring: this
| isn't unique to the CRO industry but it seems like a bigger
| problem than in other industries. I've seen US median salary
| ranges from $70,000 to $120,00 from publicly available sources
| but my time in the industry rarely demonstrated numbers that
| high. Although CRAs don't treat patients directly, it is a role
| that requires medical knowledge, attention to detailed paperwork,
| and good communication skills. There seemed to be a lot of
| cutting corners on training & hiring CRAs - e.g. hiring highly
| experienced CRAs from India and putting them into entry-level
| roles in the US on the cheap. I don't mean to say there aren't
| great experienced CRAs from India who are also great when dropped
| into an entry-level CRA role but doing so as a matter of
| unofficial policy is a bad idea: India's drug industry has a
| different regulatory environment (although there is significant
| cooperation between FDA and Indian manufacturing facilities) and,
| perhaps more importantly, there will be a wide variation in
| communication skills simply because english is a second language
| (or, in the case of India in particular, "Indian english" has
| taken on a life of its own).
|
| (4) Over-promising, under-delivering - true of any contractor
| even outside the CRA industry. Even when working on a fixed price
| basis, there are perpetual "change orders" and arguments over
| change orders.
|
| Side-note: if you want to learn more about the process by which
| drugs come to market, I strongly recommend _New Drugs_ by
| Lawrence T. Friedhoff. It 's short and the HN crowd won't have
| any problem understanding. Amazon link:
| https://www.amazon.com/New-Drugs-Insiders-Scientists-Investo...
|
| * "Unique" problems in the sense that they were personality-
| based. I won't go into specifics nor do I wish to speak
| negatively of my prior employer who, to their credit, took a
| chance on me that just happened to not work out. But I will give
| some general advice: if, during a job interview or in early
| conversations, senior management insults his/her own family _and_
| dumpsters their own employees, you 're going to have a bad time.
| esel2k wrote:
| I would add to your list of problems: Decades of easy-money
| milk-the-cow style companies (Often CROs) with very outdated
| systems with folks sittings in cheap countries to do some data
| change requests and manual tests. Truely horrible and outdated
| tech, mixed with bad salaries, high turnover and bad
| management. I used to work for a company were because of
| timezone issues a wrong date was entered, CRA requested
| correction (edit manually, sign, scan) and wrong assumptions
| etc we had to change 7 times the whole thing and send CRA
| onsite and recorrect the mess. In short: Inefficient mess.
|
| I left that industry quickly and can say I that others are
| better. Lab tracking is way better with diagnostic samples with
| private labs or when mixed with good logistics partners. It is
| not everywhere as bad as this.
|
| TLDR: add outdated tech, greed and bad management
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