9 ms·

Having worked in the pharma industry, this article is complete bullshit. For double and triple blind (the third blind comes from not even the pharma company k

• CodeMage 14y ago
  I encourage you to post that in the comments on the blog itself. There are already comments saying "thank you for this" and "placebos should be regulated" and whatnot. Maybe I'm overly optimistic, but I believe it would be useful to have your comment close to the article text (instead of having to scroll down) to provide balance.
• hellerbarde 14y ago
  I was about to write something similar. Thanks for formulating it so eloquently. I think it's this part that trips up some people: > [...] at a minimum it unblinds the doctors on the ground. It's very important that the person administering the drug/monitoring the patient can not tell the difference.
  • abtinf 14y ago
    The effects of unblinded doctors can be catastrophic and might not even be discovered. There was one study where a drug was designed to improve motor response in patients with retarded motor skills. The doctors had found a way to determine which patient was receiving which drug. So when it came time for the doctors to measure efficacy of the drug, they would do the motor skills test. If the patient was on the actual drug, and didn't show improvement, the doctors had a tendency to say things like "Well, that can't be right. Let me run the test again." Disaster. Hundred million dollar trial down the toilet.
    • jeremyarussell 14y ago
      "The doctors had found a way to determine which patient was receiving which drug." - This implies that they consciously tried to bypass their blindness, physical design of the pill being different would do this sure, but that's not an issue with too much disclosure, that's an issue with people either A) Not doing their job well enough(the pill designers) OR B)Trying to find out which one so they could fudge the results.(Crooked Doctors? Yeah, less disclosure will fix that right up.)
      • secabeen 14y ago
        You're attributing to malice what is more likely stupidity. Doctors with patients on experimental trials want the drugs to succeed. They expect the drugs to succeed. That impacts their evaluations.
      • jff 14y ago
        If I were a doctor participating in a study like this, I'd have a really hard time not trying to figure out who had the drug and who didn't. It's a secret; humans love secrets, and a doctor is extremely well-suited to figure this one out.
      • tptacek 14y ago
        Your argument here basically questions the whole idea of blinded studies ("Who cares if doctors will figure out which medication is the placebo?", it suggests; "After all, that only matters if doctors are crooked.") But you're replying to a comment that lays out a scenario in which 8-9 figure clinical trials were ruined by the incidental outcome of reasonable honest doctors accidentally unblinding studies.
        • jeremyarussell 14y ago
          I don't mean more disclosure to the doctors on the pills, if that's what you thought, which I'm only assuming because I wasn't attempting to question the validity of clinical trials at all. I was saying given the language the person I was replying to used, it seemed like the doctors were actively trying to figure out what which pills were which, evidenced by the fact that instead of going "dang, we accidentally figured it out and now are susceptible to bias. We should start the trials over right NOW instead of wasting money" They went, lets retest these patients since the outcome isn't coming out like we think it should, something they should know isn't going to fly. Also not saying specifically that it was malice, but that it's either malice or stupidity, or both. Also, I have ethical and intellectual standards of doctors doing things that will impact hundreds of thousands of people. Not sure why you said "Who cares if doctors will figure out which medication is the placebo?" - Since I didn't even insinuate that.
• jpablo 14y ago
  Of course we can't know who is telling the truth since ingredients on placebos are not disclosed. That's the part I think is the meat of the issue.
  • jennyjitters 14y ago
    >That's the part I think is the meat of the issue. I agree. I think the main issue the author wants the reader to take away is that since the ingredients in placebos are not disclosed, what's to say they can't add ingredients that will skew the results? I'm not saying that this happens, but what is stopping them? They obviously have financial, and other, incentives for their drugs to succeed, so why not take that extra measure to maintain integrity in studies that use placebos?
• pygy_ 14y ago
  Who controls the integrity of placebos?
  • refurb 14y ago
    If by "integrity" you mean "ensuring that the appropriate placebo was used in a clinical trial that was the basis of a drug approval", the answer is: the FDA.
• jarito 14y ago
  I think you may have missed the point. You have stated that the article 'pointed out a few random oversights', but the actual point of the article is that _there is no data_. How can anyone, including you, know how effective the choice of placebo ingredients are if they aren't disclosed? It doesn't seem an undue burden to ask that the placebo ingredients be documented so that their effect on the study, which is critical by any measure, can be understood. How can a separate group reproduce the results of a study if they don't have this type of information? What you seem to have said is - trust us. We won't tell you what's going on, you can't evaluate how well we are doing, but this is a totally hard problem so don't worry about it. This is disingenuous when the drug companies have vested interests in the outcome of these studies. If the drug companies are truly doing such a great job, then they should be recognized for the excellent work. The only way to do that is to release the ingredients used in the creation of placebos.
  • refurb 14y ago
    I don't think he's saying "trust us", he's saying "this is an issue that everyone knows about, thus it's a non-issue". When you submit a drug for approval at the FDA, you need to list in exacting detail exactly how trials were run, including how they were blinded. The ingredients and form of the placebo are critical for this. The paper referenced in this blog post examined journal articles to determine if the composition of the placebo was reported. Journal article are notoriously lacking in details and they have to be since no one want to read an article with pages upon pages of details. If his comment was "Hey, you guys who write papers on clinical trials, it would be awesome if you'd list the placebo composition, since I'd be more likely to believe your findings" I would say "fair point". But the blog post says "Hey! Drug companies are trying to pull a fast on all of you! Beware of what's in your medicine cabinet" which is a completely ridiculous statement. This "missing information" is available to the people that matter (the FDA). This is truly an example of making a mountain out of a molehill.
    • jeremyarussell 14y ago
      "This "missing information" is available to the people that matter (the FDA)." - That's right, I'm just too unimportant and stupid to be trusted to look at this stuff, also when the issue a lot of people are having is not being able to trust big pharma and the FDA, well hiding stuff isn't going to fix that. Yes, I was being a bit dramatic for impact.
• adaml_623 14y ago
  You've missed the point. Once the placebo has been designed to 'match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects' it should still be described in the final paper.
  • droithomme 14y ago
    Yes. If a placebo has active ingredients, you have no chance to replicate the study if you can't tell what those active ingredients are. And if you can't replicate a published study from the details given in the paper, then it's not a scientific study, it's bullshit. Yes, that's right, it's bullshit. And yes most studies fall into this category. Can't be replicated, shouldn't have been accepted for publication in the first place.
• Havoc 14y ago
  OK, but what do you measure the results against then if you distorted the benchmark with active ingredients? Surely the entire point of the control group is that it represents the unaltered baseline?
  • abtinf 14y ago
    This is a common misconception. In fact, there are very few studies in which patients receive an "inert" placebo. Consider a new drug that claims to treat heart disease. It would be obviously immoral to say, "we are going to take drugs away from the control group and give them sugar pills instead". So a "Placebo" is usually the current standard-of-care, which might be a very powerful drug. This works because we are not at all interested in the absolute effectiveness of a drug; we are only interested in whether or not it is better then the current alternatives.
    • moioci 14y ago
      You're describing an active-control trial, not a placebo-controlled trial. In a trial of drug A (current standard of care) vs. drug B (new agent), there will usually be 2 placebos involved. Participants will be randomized to receive drug A + placebo B or, conversely, placebo A + drug B. Typically the manufacturer of each drug is in the best position to produce an identical appearing placebo for each pill.
    • jessriedel 14y ago
      What moioci said. I don't believe > "Placebo" is usually the current standard-of-care is correct, either as popularly understood or as actually used during drug trials. Instead, "Placebo" is a device to make the experience of not taking a drug identical to taking a drug, which means both that it's a physical pill and that it causes the appropriate side effects.
• ahoyhere 14y ago
  Why does the placebo complexity make a call for regulation and study disclosure "utter bullshit"?
  • tptacek 14y ago
    Again: it didn't simply call for "regulation" and "disclosure". It overtly accused pharma companies of using active placebos for marketing purposes, of haphazardly endangering participants in trials, and then later suggested that the whole concept of active placebos might reasonably be outlawed. The post we're commenting on made a series of outlandishly ignorant assertions. That there are reasonable challenges we might make to the way active placebos are handled does not make the article better. You're a great writer. Maybe you should write a good article on the perils of undisclosed/underdisclosed active placebos? Because this particular article doesn't appear to be good.
• crpatino 14y ago
  While the article might have pulled a few cheap shots at pharma companies, the point stands. We need disclosure of this incredibly complex placebo matching methodology (for lack of a better term), at minimum because the experiments cannot be replicated by a third party without it. Another reason for disclosure is the ethical risk assessment. What is to prevent a misguided executive from arranging a placebo with minimal doses of active components that produce adverse effects... just to push the results of a marginally effective drug. I am sure that 99.9% of people in the industry would not do that, but there is no reason to avoid putting checks and balances in place, for the day when some random sociopath decides to push it a little bit and get away with it.
  • jessriedel 14y ago
    Do we know if it hasn't been disclosed in FDA filings (which are way more detailed), or just that it was disclosed in these research articles? Journal articles are meant to be terse for readability, and standard placebo techniques are just the sort of thing I would expect to be left out.
• samstave 14y ago
  So didn't you just state that a placebo needs to cause side effects? Doesn't that mean that it's poison by nature if said side effects are negative? Screw wanting to take part in that. "Here's a pill that will cause oily discharge and nothing else" Yum!
  • saraid216 14y ago
    Everything is poison by nature. Everything has negative side effects.
  • dalke 14y ago
    Not all side effects are equally negative. Some negative side effects are acceptable and ethical. Let's take DMSO as an example. Treatments with DMSO leave a particular garlic-like taste in the mouth. This is a negative side-effect. But DMSO is not a poison during normal treatments any more than ethyl alcohol is a poison. A good placebo for DMSO would have the same side-effects as otherwise a patient and perhaps even the doctor could tell the difference based on taste/smell compared to the anticipated taste/smell. I believe this still isn't possible, which makes testing DMSO difficult. One solution, for example, is to look for a dose-response curve, which is a more complicated signal to extract.
• samstave 14y ago
  So didn't you just state that a placebo needs to cause side effects? Doesn't that mean that it's poison by nature if said side effects are negative? Screw wanting to take part in that. "Here's a pill that will cause oily discharge and nothing else" Yum!
• samstave 14y ago
  So didn't you just state that a placebo needs to cause side effects? Doesn't that mean that it's poison by nature if said side effects are negative? Screw wanting to take part in that. "Here's a pill that will cause oily discharge and nothing else" Yum!
• bigfudge2 14y ago
  Agreed the article is bullshit. However getting the issue 100% backwards the author actually raises an important point. Active placebos do make for a different comparator than inert placebos --- arguably a much better one. Given that north of 90% of patients and doctors have been found to correctly guess allocation in blinded trials of tricyclic antidepressants and other antipsychotics, it might actually help to add something to the placebo which does generate side effects to make it harder for people to pick which group they are in. It always made me laugh reading about 'double blinded' trials of cannabis extract for MS... In this and many other cases the blind is a complete fiction.
• Xion 14y ago
  > (...) as if though drug trials aren't already expensive enough, retarding scientific progress and costing millions of lives from drugs that would have been otherwise developed. Isn't testing a vital part of this development, and by extension a crucial part of what you call scientific progress? The fact that we need more and more sophisticated testing techniques is because we understand more about the intricacies of human body and the ways it can interfere with treatment process. Placebo is an obvious example of such interference. To me, calling a scrupulous testing process a factor that's retarding scientific progress is like saying QA is retarding software progress.
• einhverfr 14y ago
  > A placebo must match the drug in physical appearance, taste, texture, density, state (liquid/solid/gas), and anticipated side effects. This makes the following statement: "When compared to a placebo, this drug had rare incidents of the following side effects..." translate as "We guessed correctly at the incidents of side effects before we started the trials," correct? If so, then that's false advertising.
• z92 14y ago
  "A placebo must match the drug's ... anticipated side effects" --- that's what he is saying too. Placebos are not inert as I had been assuming till date. And then comes the after story...
• mapt 14y ago
  Not necessarily true; The veil of ignorance can be induced for doctors, if some care is taken. Direct psychological effects of the pill's appearance on patients can't be measured, but the effect of the doctors spoiling the study based on that certainly can. Doctor hands patient sealed opaque pill blister pack, tells them to take two, nurse watching on a CCTV or via webcam sends a text message that they've verified the patient taking the pill.