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[00:00:00.320 --> 00:00:02.720] So, when I ask, what is Odoo?
[00:00:02.720 --> 00:00:04.240] What comes to mind?
[00:00:04.240 --> 00:00:06.880] Well, Odoo is a bit of everything.
[00:00:06.880 --> 00:00:14.000] Odo is a suite of business management software that some people say is like fertilizer because of the way it promotes growth.
[00:00:14.000 --> 00:00:22.480] But you know, some people also say Odoo is like a magic beanstalk because it grows with your company and is also magically affordable.
[00:00:22.480 --> 00:00:29.200] But then again, you could look at Odoo in terms of how its individual software programs are a lot like building blocks.
[00:00:29.200 --> 00:00:31.840] I mean, whatever your business needs.
[00:00:31.840 --> 00:00:34.720] Manufacturing, accounting, HR programs.
[00:00:34.720 --> 00:00:39.040] You can build a custom software suite that's perfect for your company.
[00:00:39.040 --> 00:00:40.800] So what is Odoo?
[00:00:40.800 --> 00:00:43.840] Well, I guess Odoo is a bit of everything.
[00:00:43.840 --> 00:00:49.440] Odo is a fertilizer, magic beanstock building blocks for business.
[00:00:49.440 --> 00:00:51.040] Yeah, that's it.
[00:00:51.040 --> 00:00:54.800] Which means that Odoo is exactly what every business needs.
[00:00:54.800 --> 00:00:57.760] Learn more and sign up now at odo.com.
[00:00:57.760 --> 00:01:00.160] That's odoo.com.
[00:01:00.160 --> 00:01:03.200] I chose FDU for my education for numerous reasons.
[00:01:03.200 --> 00:01:12.080] The first being the great reputation that the Silverman College of Business has, the amazing culture with the faculty and staff, and also the very convenient location to New York City.
[00:01:12.080 --> 00:01:16.320] I seized the moment at FDU and now I'm in the career of my dreams.
[00:01:16.320 --> 00:01:21.840] Ford was built on the belief that the world doesn't get to decide what you're capable of.
[00:01:21.840 --> 00:01:22.560] You do.
[00:01:22.880 --> 00:01:26.400] So ask yourself: can you or can't you?
[00:01:26.400 --> 00:01:31.120] Can you load up a Ford F-150 and build your dream with sweat and steel?
[00:01:31.120 --> 00:01:34.880] Can you chase thrills and conquer curves in a Mustang?
[00:01:34.880 --> 00:01:39.360] Can you take a Bronco to where the map ends and adventure begins?
[00:01:39.360 --> 00:01:43.440] Whether you think you can or think you can't, you're right.
[00:01:43.440 --> 00:01:44.320] Ready?
[00:01:44.320 --> 00:01:45.120] Set.
[00:01:45.120 --> 00:01:46.320] Forward.
[00:01:53.360 --> 00:02:00.600] It is Thursday, the 5th of June, 2025, and you're listening to Skeptics with a K, the podcast for science, reason, and critical thinking.
[00:02:00.920 --> 00:02:11.720] Skeptics with a K is produced by Skeptic Media in association with the Merseyside Skeptic Society, a non-profit organization for the promotion of scientific skepticism on Merseyside around the UK and internationally.
[00:02:11.720 --> 00:02:13.080] I'm your host, Mike Hall.
[00:02:13.080 --> 00:02:14.200] With me today is Marsh.
[00:02:14.200 --> 00:02:14.680] Hello.
[00:02:14.680 --> 00:02:15.480] And Alice.
[00:02:15.480 --> 00:02:15.960] Hello.
[00:02:15.960 --> 00:02:16.760] It's fucking June.
[00:02:16.760 --> 00:02:17.560] When did that happen?
[00:02:17.720 --> 00:02:18.040] It's June.
[00:02:18.040 --> 00:02:19.480] It's fucked until halfway through the year.
[00:02:19.480 --> 00:02:19.960] But you know what?
[00:02:20.040 --> 00:02:21.640] It doesn't even feel like June.
[00:02:22.200 --> 00:02:23.000] It doesn't.
[00:02:23.000 --> 00:02:24.840] It doesn't feel like it's been that long.
[00:02:24.840 --> 00:02:28.280] If someone said to me it's been six months since New Year, I say bullshit.
[00:02:28.280 --> 00:02:28.520] That's it.
[00:02:28.520 --> 00:02:28.840] Absolutely.
[00:02:29.640 --> 00:02:33.880] I'd say it feels like it's mid-April, mid-May at bus, rather.
[00:02:34.520 --> 00:02:42.040] Anyway, we'll start off today with an email from Susan, not from Sudan, which is what my phone decided to auto-correct this to.
[00:02:42.360 --> 00:02:44.120] Do you know Susan is in Sudan?
[00:02:44.440 --> 00:02:46.520] In fairness, maybe Susan is in Sudan.
[00:02:46.520 --> 00:02:49.640] It might be both from Susan and from Sudan.
[00:02:49.640 --> 00:02:50.360] I don't know.
[00:02:50.360 --> 00:02:54.600] But I think it is just from Susan, who wrote, I'm a huge fan of your show.
[00:02:54.600 --> 00:02:54.920] Ah.
[00:02:55.080 --> 00:02:56.360] Which is a strong start, Susan.
[00:02:56.520 --> 00:02:56.680] Nice.
[00:02:57.480 --> 00:02:57.960] That's the way.
[00:02:57.960 --> 00:02:58.680] Keep that up.
[00:02:58.680 --> 00:02:59.560] Susan continues.
[00:02:59.560 --> 00:03:01.000] I'm a huge fan of your show.
[00:03:01.000 --> 00:03:01.880] Anyway.
[00:03:02.200 --> 00:03:04.840] Okay, we're moving on from that very quickly.
[00:03:04.840 --> 00:03:05.240] Okay.
[00:03:05.240 --> 00:03:06.440] I'm a huge fan of your show.
[00:03:06.440 --> 00:03:14.600] Anyway, I read the following article: Efficacy of Open Label Placebos for Pre-menstrual Syndrome, a Randomized Controlled Trial.
[00:03:14.600 --> 00:03:18.840] And I thought it was a job for Mike, which is a great email.
[00:03:18.840 --> 00:03:19.720] I like that email.
[00:03:19.720 --> 00:03:21.000] It's straight to the fucking point.
[00:03:21.320 --> 00:03:22.600] There's no dicking around.
[00:03:22.600 --> 00:03:26.520] We have a little bit of pleasantries, but then just get straight onto the meat of it.
[00:03:26.680 --> 00:03:29.560] Classic academic email that is straight in, bam.
[00:03:29.560 --> 00:03:30.360] And I like this.
[00:03:30.360 --> 00:03:36.200] Looks like a job for Mike, like I'm a fucking superhero, like I'm like I'm placebo man.
[00:03:36.240 --> 00:03:43.000] Like, I've got no superpowers, but if I tell you you've got superpowers, you're more likely to report that I have superpowers to say people.
[00:03:43.400 --> 00:03:48.560] We must have a listener who can draw Mike in a placebo man, superhero costume.
[00:03:48.880 --> 00:03:56.480] I mean, it either sounds like it's a job for you in a superhero way, or that she's just assigning tasks as some sort of like line manager.
[00:03:56.480 --> 00:03:57.760] Which I'm fine either way.
[00:03:58.240 --> 00:03:59.200] Either way, that works.
[00:03:59.200 --> 00:04:04.720] I mean, I'm doing the story regardless of whether I'm a placebo man or a lowly subordinate.
[00:04:05.040 --> 00:04:07.040] Either way, this is how this is going.
[00:04:07.040 --> 00:04:11.760] So, this was a paper which was published, or will be published, as it is a preprint.
[00:04:11.760 --> 00:04:17.600] This is a paper that was published in the journal BMJ Evidence-Based Medicine, which is a journal from the British Medical Journal.
[00:04:17.600 --> 00:04:23.200] And it investigated the use of open-label placebos as an intervention for premenstrual syndrome.
[00:04:23.200 --> 00:04:30.000] Largely redundant sentence, as you should have gathered that from what we've talked about over the last 30 to 45 seconds.
[00:04:30.000 --> 00:04:45.120] We've talked about open-label placebo on the show before, and it's one of the areas that's currently being pushed by the placebo effect fans to try and work around one of the larger objections that people have to the use of placebos in clinical care.
[00:04:45.120 --> 00:04:52.240] Because the main objection to the use of placebos clinically is that it is unethical to offer a treatment without informed consent.
[00:04:52.560 --> 00:04:54.960] So, back in the day, doctors did this a lot.
[00:04:54.960 --> 00:05:01.680] They had this very paternalistic view of you just do as the doctor says, and you don't worry too much about what it is.
[00:05:01.680 --> 00:05:07.120] And we've moved away from that as an approach, and I think that's the right thing for us to have done that.
[00:05:07.120 --> 00:05:19.200] But that also means that doctors are now not able to slip you a crafty placebo and say this is a powerful drug, at least not outside the realm of a clinical trial where they still are allowed to do that.
[00:05:19.200 --> 00:05:23.120] But that's part of the contract of signing up for a trial: we might lie to you.
[00:05:23.120 --> 00:05:24.800] We're going to lie to you constantly, yeah.
[00:05:24.120 --> 00:05:33.080] Yeah, classically, however, it was thought that for a placebo to work, you had to lie to the patient and tell them it is a powerful drug.
[00:05:29.840 --> 00:05:36.680] You can't say, I'm going to give you these tablets and they're not going to do anything.
[00:05:36.920 --> 00:05:53.080] Frankly, you just need some rest, and I'm only giving you these to get you out of my office, which is often why doctors would give out placebos, or more realistically, what they did was give out antibiotics even when it wasn't appropriate because it's not going to do you any harm, but it makes you feel like you've been patiently having antibiotic risks.
[00:05:53.240 --> 00:05:57.960] It's just going to do the society harm by creating antimicrobial resistance.
[00:05:59.000 --> 00:06:15.480] So, to address this criticism of placebos, a few researchers, notably Ted Kapchuk, although he isn't involved in the particular paper we're talking about today, but a few researchers started investigating this idea of the open-label placebo, where you give somebody a placebo, but tell them it's a placebo.
[00:06:15.480 --> 00:06:18.760] So, there's no deception and therefore no ethical problem.
[00:06:19.160 --> 00:06:20.280] Totally fine.
[00:06:20.600 --> 00:06:22.040] No deception at all.
[00:06:22.040 --> 00:06:23.320] No, not at all.
[00:06:23.320 --> 00:06:26.840] But there are still problems with this approach of open-label placebos.
[00:06:26.840 --> 00:06:35.640] First, there are several components of placebo responses that you will continue to observe regardless of what the patient believes.
[00:06:35.640 --> 00:06:38.120] So, natural immunity, for example.
[00:06:38.120 --> 00:06:47.720] If you've got a patient with a cold and you give them a placebo, it doesn't matter whether they believe the placebo is a powerful drug or whether they know it's a placebo, their cold is going to get better, yeah.
[00:06:48.040 --> 00:06:52.120] Doesn't fucking matter what they believe because colds just get better anyway.
[00:06:52.440 --> 00:07:00.360] There's no reason to expect a placebo response will fall away to zero just because the patient knows they're getting a placebo, their immune system still works.
[00:07:00.360 --> 00:07:00.760] Yeah, yeah.
[00:07:01.720 --> 00:07:23.200] Second, while these studies are characterized as placebos without deception, usually when the placebo is administered, it is accompanied with a long pre-written script about how brilliant placebos are and how the placebo affect is so powerful and that invokes these mind-body healing processes, which I would argue is just as deceptive.
[00:07:23.360 --> 00:07:25.200] Massive priming, yeah.
[00:07:25.440 --> 00:07:31.040] We don't know that placebos do any such thing, and we don't even know what a mind-body healing process is.
[00:07:31.040 --> 00:07:39.520] That is just straight woo terminology that they drop into these priming statements that they put into placebo effect research.
[00:07:39.840 --> 00:07:54.000] In fact, often demonstrating that placebos can have powerful clinical effects is what these studies are trying to demonstrate, and they are assuming their conclusion as part of the study, part of the rationale of the study.
[00:07:54.640 --> 00:08:06.320] And even if we found some phrasing which manages to avoid making deceptive and misleading claims, it still introduces priming as a bias into the study.
[00:08:06.320 --> 00:08:14.880] So, priming is an effect in psychology where you introduce an initial stimulus into the system, which then influences some subsequent stimulus.
[00:08:14.880 --> 00:08:29.760] So, for example, you might say to somebody, you might hear a noise in the night, and as soon as you've said that, they are more likely to report hearing a noise in the night, even if the same noise would have passed without remark if they weren't primed to listen for it.
[00:08:29.760 --> 00:08:31.760] Could you do negative priming?
[00:08:31.760 --> 00:08:35.760] This is a placebo, it does these things, but you're not going to get better from it.
[00:08:35.760 --> 00:08:37.360] It's not going to work for you.
[00:08:37.360 --> 00:08:40.880] And then if the placebo still works, maybe they'll have a no, it's not going to work.
[00:08:42.240 --> 00:08:44.320] And that's just testing reverse psychology.
[00:08:44.320 --> 00:08:45.760] Yeah, but yeah, that's true.
[00:08:45.760 --> 00:08:48.480] Just testing the patient, going, no, I fucking am going to get better.
[00:08:48.480 --> 00:08:49.920] Thank you very much.
[00:08:50.240 --> 00:08:57.600] But probably my biggest issue with the open label placebo studies is that open label is the same thing as we didn't do any blinding.
[00:08:57.600 --> 00:08:58.400] Yeah, yeah.
[00:08:58.400 --> 00:09:04.680] And there are good reasons that we blind studies because of effects like priming, which can bias the result of our study.
[00:09:05.000 --> 00:09:18.440] But this very, very basic element of trial design is not only tolerated in placebo effect research, they rebrand it as a feature, as a positive thing, and say, look, we're doing it without blinding and it works.
[00:09:18.440 --> 00:09:19.160] Wow.
[00:09:19.480 --> 00:09:22.680] It's like, no, that's, of course, it works without blinding.
[00:09:22.680 --> 00:09:25.400] That's why we fucking do blinding.
[00:09:26.360 --> 00:09:32.040] But honestly, you know, they say if we discard this major control, it turns out things work differently.
[00:09:32.040 --> 00:09:34.440] Well, that's not a fucking shock, Ted, right?
[00:09:34.440 --> 00:09:36.360] That's why we had a control in the first place.
[00:09:36.360 --> 00:09:41.720] So with all that said, let's look at this paper specifically and see what it's maybe.
[00:09:41.720 --> 00:09:43.240] This is the paper that changes my mind.
[00:09:43.560 --> 00:09:44.360] Maybe this is the one.
[00:09:44.360 --> 00:09:46.280] You've always got to keep an open mind to that.
[00:09:46.600 --> 00:09:55.320] So 150 women aged between 18 and 45 who were struggling with either PMS or PMDD were recruited.
[00:09:55.320 --> 00:10:09.320] So PMS or pre-menstrual syndrome, as I'm sure listeners are aware, is a range of symptoms, typically including anxiety, depression, mood swings, breast tenderness, insomnia, which are commonly experienced in the run-up to menstruation.
[00:10:09.640 --> 00:10:12.440] PMDD, people might not be as familiar with.
[00:10:12.440 --> 00:10:17.320] This is pre-menstrual dysphoric disorder, which is PMS on steroids.
[00:10:17.320 --> 00:10:20.120] Not literally on steroids, but metaphorical steroids.
[00:10:20.280 --> 00:10:22.360] Not least because steroids might actually help some of the symptoms.
[00:10:23.800 --> 00:10:28.840] So it's PMS, but everything's dialed up to 11, which can be seriously debilitating.
[00:10:29.400 --> 00:10:33.240] It can be really, really serious, including suicidal ideation.
[00:10:33.640 --> 00:10:35.560] It can get that bad.
[00:10:36.200 --> 00:10:45.000] So, 150 women aged between 18 and 45 who suffer with either PMS or PMDD were recruited, and they were randomly assigned into one of three groups, right?
[00:10:46.160 --> 00:10:49.040] The first group was given open-label placebo.
[00:10:49.040 --> 00:10:53.440] So, it was two dummy pills that they would take every day for six weeks.
[00:10:53.760 --> 00:11:01.040] The placebos were, of course, accompanied by a treatment rationale, as is always the case in the open-label placebo studies.
[00:11:01.040 --> 00:11:04.320] They told the patients that placebo effects can be large.
[00:11:04.320 --> 00:11:04.800] Okay.
[00:11:04.800 --> 00:11:10.720] They told the patients placebo effects work without deception, even though that's what the study is trying to demonstrate.
[00:11:10.720 --> 00:11:11.920] Yeah, yeah, yeah, yeah.
[00:11:11.920 --> 00:11:14.880] They told them placebo effects work without deception.
[00:11:14.880 --> 00:11:18.720] They said placebos may decrease PMS symptoms.
[00:11:18.720 --> 00:11:21.600] May is doing a lot of heavy lifting in that sentence.
[00:11:21.600 --> 00:11:26.560] It's like it may do that, it may cause monkeys to spring out of your ass as well.
[00:11:26.560 --> 00:11:27.520] But probably won't.
[00:11:27.760 --> 00:11:28.480] Probably won't.
[00:11:28.480 --> 00:11:29.040] Yeah.
[00:11:29.360 --> 00:11:36.640] Placebo accounts for 40% of the improvements seen in PMS studies, was another thing that they were told.
[00:11:36.640 --> 00:11:39.440] Okay, so you're going to get better, and it's mostly because of this thing, anyway.
[00:11:39.680 --> 00:11:40.480] So you'll be fine.
[00:11:41.120 --> 00:11:52.480] And they were then shown an NBC news report, a historic NBC news report, about how brilliant placebos are, which was looking, I think, I haven't got this in my notes, but I think it was one of Ted Kapchuk's studies on IBS.
[00:11:52.720 --> 00:11:55.760] And it was a news report on that that they were shown.
[00:11:55.760 --> 00:11:57.120] Fucking Ted Kapchuck, man.
[00:11:57.120 --> 00:11:58.400] Jesus Christ.
[00:11:58.400 --> 00:12:04.000] Very, very much priming the audience to expect some sort of changes there, I would argue.
[00:12:04.160 --> 00:12:09.200] But also specifically priming them to get the thing that you're investigating.
[00:12:09.440 --> 00:12:11.200] You're actually looking for, yeah.
[00:12:11.200 --> 00:12:27.200] So I would argue that, like the noise in the night, this priming leads patients to notice small variations in their condition and report on those, even if those changes would have been so trivial that they would have gone unnoticed otherwise.
[00:12:27.520 --> 00:12:28.880] So, that's the first group, right?
[00:12:28.880 --> 00:12:30.680] Open label placebo with priming.
[00:12:30.680 --> 00:12:31.400] That's the first group.
[00:12:29.840 --> 00:12:35.400] The paper refers to this as the OLP plus group.
[00:12:36.360 --> 00:12:44.440] The second group gets the same placebo, the same dose, but doesn't get the priming, doesn't get the treatment rationale, right?
[00:12:44.440 --> 00:12:46.840] They refer to this as the OLP-minus group.
[00:12:46.840 --> 00:12:48.120] Makes sense.
[00:12:48.440 --> 00:12:52.680] And the final group, well, the final group's a bit odd.
[00:12:52.680 --> 00:12:56.520] The paper refers to this as the treatment-as-usual group.
[00:12:56.840 --> 00:13:11.640] But what actually this, what this amounts to actually is a no-treatment control, because no one in that group or in any group was taking anything for PMS and PMDD, which is not treatment as usual because people might be taking painkillers, for example.
[00:13:11.640 --> 00:13:15.640] Yeah, so the first-line therapy for PMS is typically SSRIs.
[00:13:15.640 --> 00:13:18.760] No one was taking SSRIs in this study, nobody was at all.
[00:13:18.760 --> 00:13:29.800] Some women were using hormonal contraceptives, which are used sometimes to manage PMS and PMDD, but we don't know that that's why they were taking them because they might have been taking them as a contraceptive.
[00:13:31.080 --> 00:13:40.040] It's unclear which one they were using it for, or indeed whether it was both, because quite often when you go to the doctor and they'll say, Oh, have you considered going on the pill?
[00:13:40.040 --> 00:13:44.920] Because it works as a contraceptive and it also will help stabilize you hormonally.
[00:13:45.560 --> 00:14:04.200] Some women were reported as taking paracetamol, some were taking ibuprofen, some were taking D-mannose, some were taking aspirin, some were on zinc, some were on antihistamines, some of them were taking folate, some were taking homeopathy, some were receiving acupuncture, some were having chronosacral therapy, some were taking treatment from an osteopath.
[00:14:04.200 --> 00:14:12.440] Because basically, this no treatment control, this treatment as usual group was whatever you were doing for whatever reason is fine.
[00:14:12.440 --> 00:14:15.760] And it's interesting that there's such a wide range of things, so there's 150 women.
[00:14:14.920 --> 00:14:16.320] 150 women.
[00:14:16.480 --> 00:14:27.040] And that's quite a wide range of things to come up, which also sort of nods towards the fact that there isn't a good treatment for this because medicine hasn't done a great deal of prioritizing of this as an issue.
[00:14:27.200 --> 00:14:28.320] Yeah, absolutely.
[00:14:28.320 --> 00:14:33.600] Were the two other treatment arms were people told to stop doing what they would typically do?
[00:14:33.600 --> 00:14:34.080] No.
[00:14:34.080 --> 00:14:41.760] Okay, so this was everyone could do this no matter what group they were in, they could keep taking paracetamol or stop or do whatever the fuck they wanted.
[00:14:42.080 --> 00:14:55.600] At such a small N number, you've not, unless they've done some very clever weighting, which I'm sure they haven't, and would be very, it would be near impossible to do with such a small group number.
[00:14:55.600 --> 00:15:09.840] Like, how do you know that you haven't got all your homeopathic treatments in group one, all your people taking De Manos in another group, and you know, you're actually testing one of the alternative therapies that these patients are taking?
[00:15:09.840 --> 00:15:15.200] Would that not have come out in the results afterwards if you were asking you would hope that they would list all of those things?
[00:15:16.240 --> 00:15:18.960] They do list them all and they list which women were taking them.
[00:15:18.960 --> 00:15:23.360] I don't recall if they said which groups they were in and whether there was a statistically significant.
[00:15:23.360 --> 00:15:24.960] I don't recall that analysis from the paper.
[00:15:24.960 --> 00:15:26.000] Maybe it's there and I missed it.
[00:15:26.080 --> 00:15:36.880] That feels like it would be a useful analysis because you say if all of the women who are taking a paracetamol are in the open label plus group, then what you might be discovering is the effects of paracetamol.
[00:15:37.760 --> 00:15:52.640] And you would hope that they try and evenly distribute them to some extent, but when you're distributing so many treatments plus, the demographics of those patients, there's not, you're not going to be able to do that differently, you're not randomizing that either.
[00:15:52.640 --> 00:15:54.720] Which, yeah, which makes it hard as well, right?
[00:15:54.720 --> 00:15:58.080] Because with your randomization, you want to randomize it.
[00:15:58.080 --> 00:16:10.600] You don't want to say that there are ways to randomize in a way that has some level of either weighting or you can statistically analyze that afterwards and take it out of the equation to some extent.
[00:16:10.920 --> 00:16:13.320] But I would say you need a much bigger number.
[00:16:13.320 --> 00:16:17.560] Obviously, there's a massive amount of background variation in the patients in this group.
[00:16:17.560 --> 00:16:18.760] Massive, a massive amount.
[00:16:18.760 --> 00:16:27.240] And I would personally say that it's misleading to call that a treatment as usual group, given that it was just keep doing whatever you're doing for whatever reason or stop whatever.
[00:16:27.640 --> 00:16:32.200] And some of those treatments likely aren't related to PMS and PMDD.
[00:16:32.200 --> 00:16:32.600] Yep.
[00:16:32.600 --> 00:16:33.800] But a lot of them would be.
[00:16:33.800 --> 00:16:37.160] Like D-manos, probably because they think they're getting UTIs.
[00:16:37.160 --> 00:16:38.840] UTI is typically for D-manos, yeah.
[00:16:38.840 --> 00:16:44.600] But that could be related to the bloating that they're struggling with around their period.
[00:16:44.600 --> 00:16:45.000] Yeah.
[00:16:45.320 --> 00:16:56.280] So this applied across all the groups, but no one was actually getting standard care for PMS, which says to me that there isn't really a standard care for PMS.
[00:16:56.440 --> 00:17:01.720] Yeah, so first-hand care is SSRIs, which to me sort of feels like we don't have anything good.
[00:17:01.720 --> 00:17:05.800] Maybe you're just a bit glum, have this and go away kind of thing.
[00:17:06.120 --> 00:17:10.600] But okay, I suppose in a sense, it is as usual in the sense that, you know, you carry on what you're doing.
[00:17:10.600 --> 00:17:20.920] But it's an important limitation to note that the placebo groups were on top of this very noisy background, not instead of this very noisy background.
[00:17:21.240 --> 00:17:22.040] So that's the study.
[00:17:22.040 --> 00:17:27.960] Yeah, placebo with rationale, placebo without rationale, and what they call treatment as usual.
[00:17:27.960 --> 00:17:30.440] And there were two primary outcome measures.
[00:17:30.440 --> 00:17:34.440] They were PMS symptom intensity and functional interference.
[00:17:34.440 --> 00:17:37.880] Both of these were recorded by patients filling out a symptom diary.
[00:17:37.880 --> 00:17:45.000] Yeah, which means, as you might infer from the names, a symptom diary is where you record the symptoms.
[00:17:45.200 --> 00:17:47.600] Symptom intensity is how severe they are.
[00:17:47.600 --> 00:17:51.280] Functional interference is how much it gets in the way of your day-to-day life.
[00:17:51.280 --> 00:17:51.920] Yeah.
[00:17:51.920 --> 00:17:56.080] And that's the only way you could record that because there isn't an objective measurement of those conditions.
[00:17:56.240 --> 00:17:57.200] Indeed, yeah.
[00:17:57.520 --> 00:17:59.840] There were also two secondary outcome measures.
[00:17:59.840 --> 00:18:09.280] These are psychological symptom intensity and somatic symptom intensity, which are actually subgroups of the primary outcome measure.
[00:18:09.280 --> 00:18:19.200] So they took the original symptom intensity data and split it down into psychological symptoms like mood swings, irritability, anxiety, and aggregated those as another analysis.
[00:18:19.200 --> 00:18:25.840] And then the physical symptoms like bloating, breast tenderness, headaches, and aggregated all of those into another group to analyze.
[00:18:27.600 --> 00:18:31.600] Which is reasonable and a reasonable breakdown to do.
[00:18:31.600 --> 00:18:37.920] I would like for them to have said before they did the study that they were going to do that rather than doing it after the fact.
[00:18:38.240 --> 00:18:40.800] They pre-registered the trial and said this is exactly how we're going to do the analysis.
[00:18:40.880 --> 00:18:42.000] In fairness to them, they do.
[00:18:42.000 --> 00:18:43.280] Okay, that's good.
[00:18:43.520 --> 00:18:53.440] And it is a reasonable enough disambiguation to make that you would expect if they were going to pre-register that they would pre-register that particular analysis.
[00:18:53.440 --> 00:18:55.600] And we'll touch on that a little bit more later.
[00:18:55.600 --> 00:19:00.080] I would argue these aren't true secondary measures because they're just a different way of looking at the primary data.
[00:19:00.080 --> 00:19:00.480] Yeah.
[00:19:00.480 --> 00:19:01.360] But okay, fair enough.
[00:19:01.360 --> 00:19:03.120] They're like two halves of the primary.
[00:19:03.120 --> 00:19:03.600] Yeah.
[00:19:03.920 --> 00:19:19.600] So the authors of this study conclude: so this is from the paper: administering open-label placebos with treatment rationale to women with PMS can decrease symptom intensity and interference considerably in the absence of substantial side effects with full transparency.
[00:19:19.600 --> 00:19:28.520] Considering our results, open-label placebo treatment could serve as an acceptable, efficacious, and safe intervention for PMS.
[00:19:28.160 --> 00:19:32.040] And that's such a frustrating conclusion.
[00:19:32.360 --> 00:19:43.880] I'm sure you're going to go into why it doesn't hold up, but it's a frustrating conclusion because you're already talking about something where there isn't sufficient medicalized priority to actually get something that works.
[00:19:43.880 --> 00:19:44.760] Oh, it's just women.
[00:19:44.760 --> 00:19:45.640] This happens every month.
[00:19:45.640 --> 00:19:47.000] We shouldn't worry about it, etc.
[00:19:47.240 --> 00:19:53.880] Those kind of paternalistic dismissals that drive people to go looking and seeking other treatments because they haven't got a treatment.
[00:19:53.880 --> 00:19:57.640] And now they're saying this thing that we don't have a good treatment for, it's fine.
[00:19:57.640 --> 00:19:59.560] We figured out we can give them nothing.
[00:19:59.560 --> 00:20:00.440] How empowering.
[00:20:01.480 --> 00:20:10.280] It's only more recently that we've even started to have the conversation that maybe we don't just have to put up with PMS because it's a normal part of having a period.
[00:20:10.280 --> 00:20:20.120] Likewise, painful periods have only just been part of the conversation more recently that people are recognizing that we don't just have to put up with really painful periods.
[00:20:20.120 --> 00:20:22.520] And actually, really painful periods isn't normal.
[00:20:22.520 --> 00:20:24.120] It's common, but it isn't normal.
[00:20:24.120 --> 00:20:26.600] It isn't something that you need to just live with.
[00:20:26.920 --> 00:20:32.840] So going through the raw results, there are many, many, many comparisons made in this study.
[00:20:32.840 --> 00:20:45.400] They do a comparison from baseline to OLP minus at the midpoint, from baseline to OLP minus at the end point, from baseline to OLP plus at the midpoint, from baseline to OLP plus at the end point.
[00:20:45.400 --> 00:20:49.800] For each of these, they look at symptom intensity and the functional interference scores.
[00:20:49.800 --> 00:20:55.400] And then again, for the psychological version of the intensity and the somatic version of the intensity.
[00:20:55.400 --> 00:20:58.360] So many different ways that they've carved this data up and analyzed.
[00:20:59.160 --> 00:21:10.640] The first set you were talking about there would make sense that you're doing the plus, the minus, the no treatment at midpoint and end point, but then you're doing so many different analyses at each midpoint and each endpoint for each arm.
[00:21:10.440 --> 00:21:10.800] Yeah.
[00:21:11.320 --> 00:21:18.960] But I was very happy to see that the authors of this paper have remarkably, because we see this so infrequently, adjusted for multiple comparisons.
[00:21:14.840 --> 00:21:19.280] Oh, no.
[00:21:19.520 --> 00:21:26.080] This is the first time I think I've seen a placebo paper where they have gone out and done the adjustment for multiple comparisons.
[00:21:26.080 --> 00:21:30.000] And when they did that, almost all of their significant findings disappeared.
[00:21:30.560 --> 00:21:36.960] They still report on them in the paper and say, we found this, we found this, we found this, even though they were not significant.
[00:21:36.960 --> 00:21:37.440] Wow.
[00:21:37.440 --> 00:21:41.200] So because individually they were significant before they did the multiple comparison.
[00:21:41.200 --> 00:21:41.440] Yeah.
[00:21:41.440 --> 00:21:42.400] And these were significant.
[00:21:42.400 --> 00:21:44.960] And also we did the multiple comparison thing, so we've done things the right way.
[00:21:44.960 --> 00:21:46.080] Is that essentially it?
[00:21:46.080 --> 00:21:46.640] Yeah.
[00:21:46.640 --> 00:21:53.760] So the paper still reports on several of the non-significant findings as if they were significant in the paper.
[00:21:53.760 --> 00:22:00.080] In fact, after adjustment, there are no significant findings at all for the open label placebo without rationale.
[00:22:00.080 --> 00:22:01.280] So without the priming.
[00:22:01.680 --> 00:22:08.880] Absolutely zero significant findings for that, either the midpoint, the end point, the somatic symptoms, the overall, none of it, nothing at all.
[00:22:08.880 --> 00:22:13.760] The only significant effect which remained was for the open label placebo with rationale.
[00:22:13.760 --> 00:22:17.760] And in many cases, even these were not very deep into significance.
[00:22:17.760 --> 00:22:22.480] They were like a p-value of 0.03, 0.04, that kind of thing.
[00:22:22.720 --> 00:22:27.520] Some of them were south of 0.01, but not an awful lot of them.
[00:22:27.840 --> 00:22:31.760] Now, as we've discussed, some of these outcome measures were derivative.
[00:22:31.760 --> 00:22:39.040] So if one outcome is significant, it's not really a surprise that measurements derived from that outcome will also be significant.
[00:22:39.280 --> 00:22:43.600] So the so-called secondary outcome doesn't really add very much to the study.
[00:22:43.600 --> 00:22:50.720] And I'd rather get the impression that they added these to the trial registration, assuming they wouldn't find anything.
[00:22:50.720 --> 00:22:56.880] And so saying, oh, and we're going to give ourselves the opportunity to carve up the data in several different ways later as well.
[00:22:57.200 --> 00:22:58.000] Yeah, it could be.
[00:22:58.000 --> 00:23:07.080] I don't know that that's the case, but I can so totally see a version of this paper where the primary outcome found nothing, but they said, Oh, but if you look at just the somatic symptoms, it turns out it's brilliant.
[00:23:07.320 --> 00:23:08.200] Yeah, yeah.
[00:23:08.520 --> 00:23:18.440] But that isn't what ended up happening, so the secondary measure ends up being somewhat redundant because they say overall it improves it and improves psychologically and improves somatic symptoms.
[00:23:18.520 --> 00:23:23.800] But it's perfectly reasonable to separate those out, especially on a study looking at placebo specifically.
[00:23:23.800 --> 00:23:24.200] It is, yeah.
[00:23:24.440 --> 00:23:30.280] But it's like he ran the first he ran the 100 meters quickly, and of that he ran the first 50 meters quickly and the second meters.
[00:23:30.360 --> 00:23:31.640] And the second meters quickly.
[00:23:31.640 --> 00:23:34.360] I mean, in fairness, it could have been all was in the psychological thing.
[00:23:34.600 --> 00:23:34.840] That's true.
[00:23:35.720 --> 00:23:39.160] But yeah, it just means that secondary outcome measure was largely redundant here.
[00:23:39.160 --> 00:23:47.960] But anyway, as is commonly the case when we look at placebo effect research, we have another study here which is based entirely on self-reported data.
[00:23:47.960 --> 00:23:54.600] So I would argue that the findings here are not really different to what you would expect to see if the placebo effect does not exist.
[00:23:54.600 --> 00:24:04.280] If the placebo effect is N-rays, we would still expect to see this same data, these same findings, because you've said it's going to help you.
[00:24:04.280 --> 00:24:07.800] And so any opportunity you have to say, do I feel a little bit better?
[00:24:07.800 --> 00:24:09.080] I think I probably do.
[00:24:09.080 --> 00:24:10.040] You're going to record.
[00:24:10.280 --> 00:24:12.760] Well, you're not going to, but you're more likely to.
[00:24:12.760 --> 00:24:13.160] To record it.
[00:24:13.400 --> 00:24:17.560] It probably takes that more likelihood for it to triple to start pushing things in that direction.
[00:24:17.560 --> 00:24:22.360] This isn't the brain activating some mysterious mind-body healing process.
[00:24:22.360 --> 00:24:28.920] These results can be fully accounted for by reporting bias introduced through priming.
[00:24:29.240 --> 00:24:31.800] It's not evidence of a therapeutic effect.
[00:24:31.800 --> 00:24:35.640] It's a textbook example of psychological manipulation.
[00:24:35.640 --> 00:24:46.560] In fact, it's a psychological manipulation with a major confounder, which is there's no blinding, but they've dressed that up as a desirable aspect of this study.
[00:24:47.440 --> 00:24:54.480] Demonstrating that priming and confirmation bias are a thing, which is all this study is doing, I think, doesn't really achieve anything.
[00:24:55.360 --> 00:24:59.360] There's plenty of evidence that these effects exist, they're well known, they're recorded in the literature.
[00:24:59.360 --> 00:25:07.600] People like Chris French have made entire careers on how psychological biases can impact us in unexpected ways.
[00:25:07.600 --> 00:25:14.160] And just telling somebody that a house is haunted is enough to make them report having strange experiences in that house.
[00:25:14.160 --> 00:25:22.400] And having someone in authority tell you this medicine will help is going to make you more likely to say that it has, even if nothing has changed.
[00:25:22.400 --> 00:25:23.680] That's not healing.
[00:25:23.680 --> 00:25:24.640] That's not healthcare.
[00:25:24.640 --> 00:25:24.800] Yes.
[00:25:25.520 --> 00:25:35.280] That's not why people go to the doctor to have them bamboozle you into saying you feel better regardless of any objective improvement in your condition.
[00:25:35.600 --> 00:25:48.160] It's certainly not enough to justify recommending placebos as a first-line treatment as this paper does, especially not to women who already spend far too much of their lives being told that their suffering is all in their heads.
[00:25:52.000 --> 00:25:55.440] So me and Alice have recently got back from Barcelona.
[00:25:55.440 --> 00:25:55.840] Good.
[00:25:55.840 --> 00:25:59.040] Yeah, we went off to Barcelona with the Skeptics in the Pub Online team.
[00:25:59.040 --> 00:26:00.160] We did this a couple of years ago.
[00:26:00.160 --> 00:26:02.480] So the Skeptics in the Pub Online team were fantastic.
[00:26:02.480 --> 00:26:13.200] And we met up for drinks in Munich when Igor from the team, anybody who's watched a Skeptics in the Pub Online broadcast, will know Igor because he asked all the questions and they're excellent questions.
[00:26:13.280 --> 00:26:14.400] He just asked questions.
[00:26:15.040 --> 00:26:23.760] So when Igor had managed to leave Russia, we all went to Munich to hang out with Igor and drink to him and Nadia and celebrate and everything.
[00:26:23.760 --> 00:26:28.240] And then we went back to Germany the next year, went to Clorn for Gerald's birthday, which was Gerald's 50th.
[00:26:28.320 --> 00:26:29.200] So we all went to London.
[00:26:29.520 --> 00:26:30.120] Big celebration.
[00:26:30.360 --> 00:26:32.840] We didn't get to go away last year, so we got away this year.
[00:26:32.840 --> 00:26:34.040] Was it last you went to Clorn?
[00:26:34.040 --> 00:26:35.320] Fuck me, my brain is useless.
[00:26:29.920 --> 00:26:36.280] I think it was last year.
[00:26:36.920 --> 00:26:38.920] This year, we went to Barcelona.
[00:26:38.920 --> 00:26:40.680] I can't tell you about it because we haven't been there.
[00:26:40.680 --> 00:26:41.880] We're recording this slightly.
[00:26:41.880 --> 00:26:45.960] But it's nice to get to see all of the people from Skeptics.
[00:26:45.960 --> 00:26:56.200] But I think the people going is going to be Kat and Igor and Joe and David Glass and Dave Jenkins and me and you and Brian.
[00:26:56.200 --> 00:26:57.000] Yeah, yeah.
[00:26:57.000 --> 00:26:58.840] I think that's brilliant.
[00:26:59.640 --> 00:27:00.600] Fantastic.
[00:27:00.600 --> 00:27:02.760] Oh, you're mean.
[00:27:04.360 --> 00:27:06.600] There is a planet Barcelona in Doctor Who.
[00:27:06.600 --> 00:27:06.920] Is there?
[00:27:06.920 --> 00:27:07.320] Yeah.
[00:27:07.320 --> 00:27:11.080] The doctor at one point says they're going to take you to Barcelona, but not the city, to the planet.
[00:27:11.240 --> 00:27:14.840] Was that just so you could keep up the average of saying Doctor Who on more than half a day?
[00:27:17.400 --> 00:27:19.080] I've got to try and work a little more often.
[00:27:19.400 --> 00:27:28.280] What thing is, I've got a major confounder there of every time I say Doctor Who said this, that comes up as a false positive on the Doctor Who thing.
[00:27:28.280 --> 00:27:29.400] So I need to work double hard.
[00:27:29.480 --> 00:27:31.640] It catches me every time with newspaper headlines as well.
[00:27:31.640 --> 00:27:34.440] And it goes, you know, Doctor Who murdered patients.
[00:27:34.440 --> 00:27:35.320] I go, he fucking did.
[00:27:35.560 --> 00:27:36.600] I know, I do that every time.
[00:27:36.600 --> 00:27:37.080] That's great.
[00:27:37.080 --> 00:27:37.480] That's great.
[00:27:37.480 --> 00:27:39.160] I do it to Liberty every single time.
[00:27:39.480 --> 00:27:40.120] Wow.
[00:27:40.120 --> 00:27:41.640] God, he gets about.
[00:27:41.960 --> 00:27:44.360] But no, I'm glad that Barcelona went well.
[00:27:44.760 --> 00:27:46.360] That sounds like it was a wee.
[00:27:46.440 --> 00:27:48.040] I'm sure it will have been.
[00:27:52.200 --> 00:27:53.800] So, Liverpool Skeptics at the Pub.
[00:27:53.800 --> 00:27:56.440] We have an event this evening in Dr.
[00:27:56.440 --> 00:27:57.320] Duncan's on St.
[00:27:57.320 --> 00:27:57.880] John's Lane.
[00:27:57.880 --> 00:27:59.960] And if you're in the Liverpool area, you should definitely come along to that.
[00:27:59.960 --> 00:28:01.320] That's from 8 p.m.
[00:28:01.480 --> 00:28:03.000] Meet Mike, meet the rest of the board.
[00:28:03.000 --> 00:28:04.520] Me and Alice are going to be away.
[00:28:04.520 --> 00:28:06.440] Well, we are currently away as this goes out.
[00:28:06.440 --> 00:28:07.800] But that's a fantastic time.
[00:28:07.800 --> 00:28:11.160] You know, we get together, we have drinks, we tell stories, we have some jokes.
[00:28:11.320 --> 00:28:11.880] It's a fantastic thing.
[00:28:12.200 --> 00:28:12.760] Socials are great.
[00:28:13.240 --> 00:28:14.120] They're really good fun.
[00:28:14.120 --> 00:28:14.960] It's an awesome time.
[00:28:14.960 --> 00:28:17.760] You should definitely come along to that if you were in the Liverpool area.
[00:28:14.680 --> 00:28:21.120] Also, QED, we've got tickets for QEDs are still on sale.
[00:28:21.680 --> 00:28:29.840] You can pick yours up for £179 new British pounds from the website qedcon.org, the exclusive distributor of tickets for QED.
[00:28:30.160 --> 00:28:31.440] We managed to get the rights for it again.
[00:28:31.680 --> 00:28:32.400] We somehow.
[00:28:32.880 --> 00:28:34.160] We wanted to get held up.
[00:28:34.160 --> 00:28:36.000] We've got outbid Ticketmaster on it.
[00:28:36.000 --> 00:28:37.760] How we manage that, I don't know.
[00:28:38.240 --> 00:28:39.600] You do have to be careful.
[00:28:40.000 --> 00:28:45.680] If ever we tweet, well, actually, Twitter's just fucked and broken now, so I don't think it's the case anymore.
[00:28:45.680 --> 00:28:54.000] But it used to be that if you tweeted, whenever I tweeted on Twitter that we'd sold out the dinner, you'd get loads of bots going, like, I've got tickets for this thing.
[00:28:54.000 --> 00:28:54.640] Yeah, that's right.
[00:28:55.360 --> 00:28:56.480] You can get extra spare ones.
[00:28:56.480 --> 00:28:57.120] Yeah, that was great.
[00:28:57.360 --> 00:28:59.040] Yeah, it's not how that fucking works.
[00:28:59.040 --> 00:29:04.320] So, yeah, QED is on the 25th and 26th of October at the Mercure Piccadilly Hotel in Manchester.
[00:29:04.320 --> 00:29:07.600] There's going to be a Skepticamp event that is free for everyone to attend.
[00:29:07.600 --> 00:29:09.520] You don't need a QED ticket to come along.
[00:29:09.520 --> 00:29:17.280] So if you can't come to QED itself, maybe you're busy that weekend, you can still come to Skepticamp on the Friday and say hello and meet the team.
[00:29:17.280 --> 00:29:18.480] And that's going to be a fantastic time.
[00:29:18.480 --> 00:29:24.000] Skepticamp this year being run for us once again by the fantastic folks at Skeptics in the Pob Online, which is brilliant.
[00:29:24.000 --> 00:29:25.680] David does a fantastic job.
[00:29:25.680 --> 00:29:31.760] And so we're going to be, and the rest of the team, like you know, Malcolm and Gerald and things.
[00:29:31.760 --> 00:29:33.600] So we're doing really well on that.
[00:29:33.760 --> 00:29:35.600] You should come along to that if you're in the Liverpool area.
[00:29:35.600 --> 00:29:36.800] That's on the 24th.
[00:29:36.800 --> 00:29:40.320] And almost certainly, Manchester area, rather, that's going to be on the 24th.
[00:29:40.320 --> 00:29:42.560] And almost certainly it's going to be stuff going on on the Thursday as well.
[00:29:42.640 --> 00:29:43.680] It's going to be great.
[00:29:44.000 --> 00:29:56.000] Also, if you enjoy the show and you like what we do, and you would like to support us and the time and effort that we put into this show, you could do that by joining our Patreon, which is a patreon.com forward slash skeptics with a K.
[00:29:56.000 --> 00:29:58.880] In exchange for that, you get an ad-free version of this show.
[00:29:58.960 --> 00:30:05.640] You do so without any leading advertising, it is really very much the best way to support us, and that's definitely the way that you should be going.
[00:30:05.800 --> 00:30:12.600] And we've got some people saying, I feel like I should just listen to the ads because then that's how much more entertaining than the ad-free show.
[00:30:13.240 --> 00:30:15.400] No, definitely the Patreon's a much better way to do it than that.
[00:30:15.560 --> 00:30:19.240] Throwing us a couple of quid a month, we'll do far far more than the ads.
[00:30:19.240 --> 00:30:21.080] Yeah, so it's very, very cheap to sign up.
[00:30:21.080 --> 00:30:23.800] We're not trying to upsell you and all that sort of stuff.
[00:30:23.800 --> 00:30:26.520] It really does help us out and help us keep the show going.
[00:30:26.520 --> 00:30:37.640] Also, if you like what we do with the show and what we do at Merseyside Skeptics, you can support Mercy Side Skeptics by going to their Patreon, which is patron.com forward slash Mercy Skeptics, where you will also get an ad-free version of this show.
[00:30:37.640 --> 00:30:40.920] Yeah, aside from that, then I think that is all we've got time for.
[00:30:40.920 --> 00:30:41.960] I think it is.
[00:30:41.960 --> 00:30:44.680] All that remains then is for me to thank Marsh for coming along today.
[00:30:44.680 --> 00:30:45.240] Cheers.
[00:30:45.240 --> 00:30:46.200] Thank you to Alice.
[00:30:46.200 --> 00:30:46.760] Thank you.
[00:30:46.760 --> 00:30:49.320] We have been Skeptics with a K, and we will see you next time.
[00:30:49.320 --> 00:30:50.040] Bye now.
[00:30:50.040 --> 00:30:51.000] Bye.
[00:30:55.800 --> 00:31:00.840] Skeptics with a K is produced by Skeptic Media in association with the Merseyside Skeptic Society.
[00:31:00.840 --> 00:31:09.880] For questions or comments, email podcast at skepticswithakay.org, and you can find out more about Merseyside Skeptics at mercysideskeptics.org.uk.

Prompt 2: Key Takeaways

Now please extract the key takeaways from the transcript content I provided.

Extract the most important key takeaways from this part of the conversation. Use a single sentence statement (the key takeaway) rather than milquetoast descriptions like "the hosts discuss...". 

Limit the key takeaways to a maximum of 3. The key takeaways should be insightful and knowledge-additive. 

IMPORTANT: Return ONLY valid JSON, no explanations or markdown. Ensure:
- All strings are properly quoted and escaped
- No trailing commas
- All braces and brackets are balanced
Format: {"key_takeaways": ["takeaway 1", "takeaway 2"]}

Prompt 3: Segments

Now identify 2-4 distinct topical segments from this part of the conversation.

For each segment, identify:
- Descriptive title (3-6 words)  
- START timestamp when this topic begins (HH:MM:SS format)
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Most important Key takeaway from that segment. Key takeaway must be specific and knowledge-additive.
- Brief summary of the discussion

IMPORTANT: The timestamp should mark when the topic/segment STARTS, not a range. Look for topic transitions and conversation shifts.

Return ONLY valid JSON. Ensure all strings are properly quoted, no trailing commas:
{
  "segments": [
    {
      "segment_title": "Topic Discussion", 
      "timestamp": "01:15:30",
      "key_takeaway": "main point from this segment",
      "segment_summary": "brief description of what was discussed"
    }
  ]
}

Timestamp format: HH:MM:SS (e.g., 00:05:30, 01:22:45) marking the START of each segment.

Prompt 4: Media Mentions

Now scan the transcript content I provided for ACTUAL mentions of specific media titles:

Find explicit mentions of:
- Books (with specific titles)
- Movies (with specific titles)  
- TV Shows (with specific titles)
- Music/Songs (with specific titles)

DO NOT include:
- Websites, URLs, or web services
- Other podcasts or podcast names

IMPORTANT: 
- Only include items explicitly mentioned by name. Do not invent titles.
- Valid categories are: "Book", "Movie", "TV Show", "Music"
- Include the exact phrase where each item was mentioned
- Find the nearest proximate timestamp where it appears in the conversation
- THE TIMESTAMP OF THE MEDIA MENTION IS IMPORTANT - DO NOT INVENT TIMESTAMPS AND DO NOT MISATTRIBUTE TIMESTAMPS
- Double check that the timestamp is accurate - a timestamp will NEVER be greater than the total length of the audio
- Timestamps are given as ranges, e.g. 01:13:42.520 --> 01:13:46.720. Use the EARLIER of the 2 timestamps in the range.

Return ONLY valid JSON. Ensure all strings are properly quoted and escaped, no trailing commas:
{
  "media_mentions": [
    {
      "title": "Exact Title as Mentioned",
      "category": "Book",
      "author_artist": "N/A",
      "context": "Brief context of why it was mentioned",
      "context_phrase": "The exact sentence or phrase where it was mentioned",
      "timestamp": "estimated time like 01:15:30"
    }
  ]
}

If no media is mentioned, return: {"media_mentions": []}

Full Transcript

[00:00:00.320 --> 00:00:02.720] So, when I ask, what is Odoo?
[00:00:02.720 --> 00:00:04.240] What comes to mind?
[00:00:04.240 --> 00:00:06.880] Well, Odoo is a bit of everything.
[00:00:06.880 --> 00:00:14.000] Odo is a suite of business management software that some people say is like fertilizer because of the way it promotes growth.
[00:00:14.000 --> 00:00:22.480] But you know, some people also say Odoo is like a magic beanstalk because it grows with your company and is also magically affordable.
[00:00:22.480 --> 00:00:29.200] But then again, you could look at Odoo in terms of how its individual software programs are a lot like building blocks.
[00:00:29.200 --> 00:00:31.840] I mean, whatever your business needs.
[00:00:31.840 --> 00:00:34.720] Manufacturing, accounting, HR programs.
[00:00:34.720 --> 00:00:39.040] You can build a custom software suite that's perfect for your company.
[00:00:39.040 --> 00:00:40.800] So what is Odoo?
[00:00:40.800 --> 00:00:43.840] Well, I guess Odoo is a bit of everything.
[00:00:43.840 --> 00:00:49.440] Odo is a fertilizer, magic beanstock building blocks for business.
[00:00:49.440 --> 00:00:51.040] Yeah, that's it.
[00:00:51.040 --> 00:00:54.800] Which means that Odoo is exactly what every business needs.
[00:00:54.800 --> 00:00:57.760] Learn more and sign up now at odo.com.
[00:00:57.760 --> 00:01:00.160] That's odoo.com.
[00:01:00.160 --> 00:01:03.200] I chose FDU for my education for numerous reasons.
[00:01:03.200 --> 00:01:12.080] The first being the great reputation that the Silverman College of Business has, the amazing culture with the faculty and staff, and also the very convenient location to New York City.
[00:01:12.080 --> 00:01:16.320] I seized the moment at FDU and now I'm in the career of my dreams.
[00:01:16.320 --> 00:01:21.840] Ford was built on the belief that the world doesn't get to decide what you're capable of.
[00:01:21.840 --> 00:01:22.560] You do.
[00:01:22.880 --> 00:01:26.400] So ask yourself: can you or can't you?
[00:01:26.400 --> 00:01:31.120] Can you load up a Ford F-150 and build your dream with sweat and steel?
[00:01:31.120 --> 00:01:34.880] Can you chase thrills and conquer curves in a Mustang?
[00:01:34.880 --> 00:01:39.360] Can you take a Bronco to where the map ends and adventure begins?
[00:01:39.360 --> 00:01:43.440] Whether you think you can or think you can't, you're right.
[00:01:43.440 --> 00:01:44.320] Ready?
[00:01:44.320 --> 00:01:45.120] Set.
[00:01:45.120 --> 00:01:46.320] Forward.
[00:01:53.360 --> 00:02:00.600] It is Thursday, the 5th of June, 2025, and you're listening to Skeptics with a K, the podcast for science, reason, and critical thinking.
[00:02:00.920 --> 00:02:11.720] Skeptics with a K is produced by Skeptic Media in association with the Merseyside Skeptic Society, a non-profit organization for the promotion of scientific skepticism on Merseyside around the UK and internationally.
[00:02:11.720 --> 00:02:13.080] I'm your host, Mike Hall.
[00:02:13.080 --> 00:02:14.200] With me today is Marsh.
[00:02:14.200 --> 00:02:14.680] Hello.
[00:02:14.680 --> 00:02:15.480] And Alice.
[00:02:15.480 --> 00:02:15.960] Hello.
[00:02:15.960 --> 00:02:16.760] It's fucking June.
[00:02:16.760 --> 00:02:17.560] When did that happen?
[00:02:17.720 --> 00:02:18.040] It's June.
[00:02:18.040 --> 00:02:19.480] It's fucked until halfway through the year.
[00:02:19.480 --> 00:02:19.960] But you know what?
[00:02:20.040 --> 00:02:21.640] It doesn't even feel like June.
[00:02:22.200 --> 00:02:23.000] It doesn't.
[00:02:23.000 --> 00:02:24.840] It doesn't feel like it's been that long.
[00:02:24.840 --> 00:02:28.280] If someone said to me it's been six months since New Year, I say bullshit.
[00:02:28.280 --> 00:02:28.520] That's it.
[00:02:28.520 --> 00:02:28.840] Absolutely.
[00:02:29.640 --> 00:02:33.880] I'd say it feels like it's mid-April, mid-May at bus, rather.
[00:02:34.520 --> 00:02:42.040] Anyway, we'll start off today with an email from Susan, not from Sudan, which is what my phone decided to auto-correct this to.
[00:02:42.360 --> 00:02:44.120] Do you know Susan is in Sudan?
[00:02:44.440 --> 00:02:46.520] In fairness, maybe Susan is in Sudan.
[00:02:46.520 --> 00:02:49.640] It might be both from Susan and from Sudan.
[00:02:49.640 --> 00:02:50.360] I don't know.
[00:02:50.360 --> 00:02:54.600] But I think it is just from Susan, who wrote, I'm a huge fan of your show.
[00:02:54.600 --> 00:02:54.920] Ah.
[00:02:55.080 --> 00:02:56.360] Which is a strong start, Susan.
[00:02:56.520 --> 00:02:56.680] Nice.
[00:02:57.480 --> 00:02:57.960] That's the way.
[00:02:57.960 --> 00:02:58.680] Keep that up.
[00:02:58.680 --> 00:02:59.560] Susan continues.
[00:02:59.560 --> 00:03:01.000] I'm a huge fan of your show.
[00:03:01.000 --> 00:03:01.880] Anyway.
[00:03:02.200 --> 00:03:04.840] Okay, we're moving on from that very quickly.
[00:03:04.840 --> 00:03:05.240] Okay.
[00:03:05.240 --> 00:03:06.440] I'm a huge fan of your show.
[00:03:06.440 --> 00:03:14.600] Anyway, I read the following article: Efficacy of Open Label Placebos for Pre-menstrual Syndrome, a Randomized Controlled Trial.
[00:03:14.600 --> 00:03:18.840] And I thought it was a job for Mike, which is a great email.
[00:03:18.840 --> 00:03:19.720] I like that email.
[00:03:19.720 --> 00:03:21.000] It's straight to the fucking point.
[00:03:21.320 --> 00:03:22.600] There's no dicking around.
[00:03:22.600 --> 00:03:26.520] We have a little bit of pleasantries, but then just get straight onto the meat of it.
[00:03:26.680 --> 00:03:29.560] Classic academic email that is straight in, bam.
[00:03:29.560 --> 00:03:30.360] And I like this.
[00:03:30.360 --> 00:03:36.200] Looks like a job for Mike, like I'm a fucking superhero, like I'm like I'm placebo man.
[00:03:36.240 --> 00:03:43.000] Like, I've got no superpowers, but if I tell you you've got superpowers, you're more likely to report that I have superpowers to say people.
[00:03:43.400 --> 00:03:48.560] We must have a listener who can draw Mike in a placebo man, superhero costume.
[00:03:48.880 --> 00:03:56.480] I mean, it either sounds like it's a job for you in a superhero way, or that she's just assigning tasks as some sort of like line manager.
[00:03:56.480 --> 00:03:57.760] Which I'm fine either way.
[00:03:58.240 --> 00:03:59.200] Either way, that works.
[00:03:59.200 --> 00:04:04.720] I mean, I'm doing the story regardless of whether I'm a placebo man or a lowly subordinate.
[00:04:05.040 --> 00:04:07.040] Either way, this is how this is going.
[00:04:07.040 --> 00:04:11.760] So, this was a paper which was published, or will be published, as it is a preprint.
[00:04:11.760 --> 00:04:17.600] This is a paper that was published in the journal BMJ Evidence-Based Medicine, which is a journal from the British Medical Journal.
[00:04:17.600 --> 00:04:23.200] And it investigated the use of open-label placebos as an intervention for premenstrual syndrome.
[00:04:23.200 --> 00:04:30.000] Largely redundant sentence, as you should have gathered that from what we've talked about over the last 30 to 45 seconds.
[00:04:30.000 --> 00:04:45.120] We've talked about open-label placebo on the show before, and it's one of the areas that's currently being pushed by the placebo effect fans to try and work around one of the larger objections that people have to the use of placebos in clinical care.
[00:04:45.120 --> 00:04:52.240] Because the main objection to the use of placebos clinically is that it is unethical to offer a treatment without informed consent.
[00:04:52.560 --> 00:04:54.960] So, back in the day, doctors did this a lot.
[00:04:54.960 --> 00:05:01.680] They had this very paternalistic view of you just do as the doctor says, and you don't worry too much about what it is.
[00:05:01.680 --> 00:05:07.120] And we've moved away from that as an approach, and I think that's the right thing for us to have done that.
[00:05:07.120 --> 00:05:19.200] But that also means that doctors are now not able to slip you a crafty placebo and say this is a powerful drug, at least not outside the realm of a clinical trial where they still are allowed to do that.
[00:05:19.200 --> 00:05:23.120] But that's part of the contract of signing up for a trial: we might lie to you.
[00:05:23.120 --> 00:05:24.800] We're going to lie to you constantly, yeah.
[00:05:24.120 --> 00:05:33.080] Yeah, classically, however, it was thought that for a placebo to work, you had to lie to the patient and tell them it is a powerful drug.
[00:05:29.840 --> 00:05:36.680] You can't say, I'm going to give you these tablets and they're not going to do anything.
[00:05:36.920 --> 00:05:53.080] Frankly, you just need some rest, and I'm only giving you these to get you out of my office, which is often why doctors would give out placebos, or more realistically, what they did was give out antibiotics even when it wasn't appropriate because it's not going to do you any harm, but it makes you feel like you've been patiently having antibiotic risks.
[00:05:53.240 --> 00:05:57.960] It's just going to do the society harm by creating antimicrobial resistance.
[00:05:59.000 --> 00:06:15.480] So, to address this criticism of placebos, a few researchers, notably Ted Kapchuk, although he isn't involved in the particular paper we're talking about today, but a few researchers started investigating this idea of the open-label placebo, where you give somebody a placebo, but tell them it's a placebo.
[00:06:15.480 --> 00:06:18.760] So, there's no deception and therefore no ethical problem.
[00:06:19.160 --> 00:06:20.280] Totally fine.
[00:06:20.600 --> 00:06:22.040] No deception at all.
[00:06:22.040 --> 00:06:23.320] No, not at all.
[00:06:23.320 --> 00:06:26.840] But there are still problems with this approach of open-label placebos.
[00:06:26.840 --> 00:06:35.640] First, there are several components of placebo responses that you will continue to observe regardless of what the patient believes.
[00:06:35.640 --> 00:06:38.120] So, natural immunity, for example.
[00:06:38.120 --> 00:06:47.720] If you've got a patient with a cold and you give them a placebo, it doesn't matter whether they believe the placebo is a powerful drug or whether they know it's a placebo, their cold is going to get better, yeah.
[00:06:48.040 --> 00:06:52.120] Doesn't fucking matter what they believe because colds just get better anyway.
[00:06:52.440 --> 00:07:00.360] There's no reason to expect a placebo response will fall away to zero just because the patient knows they're getting a placebo, their immune system still works.
[00:07:00.360 --> 00:07:00.760] Yeah, yeah.
[00:07:01.720 --> 00:07:23.200] Second, while these studies are characterized as placebos without deception, usually when the placebo is administered, it is accompanied with a long pre-written script about how brilliant placebos are and how the placebo affect is so powerful and that invokes these mind-body healing processes, which I would argue is just as deceptive.
[00:07:23.360 --> 00:07:25.200] Massive priming, yeah.
[00:07:25.440 --> 00:07:31.040] We don't know that placebos do any such thing, and we don't even know what a mind-body healing process is.
[00:07:31.040 --> 00:07:39.520] That is just straight woo terminology that they drop into these priming statements that they put into placebo effect research.
[00:07:39.840 --> 00:07:54.000] In fact, often demonstrating that placebos can have powerful clinical effects is what these studies are trying to demonstrate, and they are assuming their conclusion as part of the study, part of the rationale of the study.
[00:07:54.640 --> 00:08:06.320] And even if we found some phrasing which manages to avoid making deceptive and misleading claims, it still introduces priming as a bias into the study.
[00:08:06.320 --> 00:08:14.880] So, priming is an effect in psychology where you introduce an initial stimulus into the system, which then influences some subsequent stimulus.
[00:08:14.880 --> 00:08:29.760] So, for example, you might say to somebody, you might hear a noise in the night, and as soon as you've said that, they are more likely to report hearing a noise in the night, even if the same noise would have passed without remark if they weren't primed to listen for it.
[00:08:29.760 --> 00:08:31.760] Could you do negative priming?
[00:08:31.760 --> 00:08:35.760] This is a placebo, it does these things, but you're not going to get better from it.
[00:08:35.760 --> 00:08:37.360] It's not going to work for you.
[00:08:37.360 --> 00:08:40.880] And then if the placebo still works, maybe they'll have a no, it's not going to work.
[00:08:42.240 --> 00:08:44.320] And that's just testing reverse psychology.
[00:08:44.320 --> 00:08:45.760] Yeah, but yeah, that's true.
[00:08:45.760 --> 00:08:48.480] Just testing the patient, going, no, I fucking am going to get better.
[00:08:48.480 --> 00:08:49.920] Thank you very much.
[00:08:50.240 --> 00:08:57.600] But probably my biggest issue with the open label placebo studies is that open label is the same thing as we didn't do any blinding.
[00:08:57.600 --> 00:08:58.400] Yeah, yeah.
[00:08:58.400 --> 00:09:04.680] And there are good reasons that we blind studies because of effects like priming, which can bias the result of our study.
[00:09:05.000 --> 00:09:18.440] But this very, very basic element of trial design is not only tolerated in placebo effect research, they rebrand it as a feature, as a positive thing, and say, look, we're doing it without blinding and it works.
[00:09:18.440 --> 00:09:19.160] Wow.
[00:09:19.480 --> 00:09:22.680] It's like, no, that's, of course, it works without blinding.
[00:09:22.680 --> 00:09:25.400] That's why we fucking do blinding.
[00:09:26.360 --> 00:09:32.040] But honestly, you know, they say if we discard this major control, it turns out things work differently.
[00:09:32.040 --> 00:09:34.440] Well, that's not a fucking shock, Ted, right?
[00:09:34.440 --> 00:09:36.360] That's why we had a control in the first place.
[00:09:36.360 --> 00:09:41.720] So with all that said, let's look at this paper specifically and see what it's maybe.
[00:09:41.720 --> 00:09:43.240] This is the paper that changes my mind.
[00:09:43.560 --> 00:09:44.360] Maybe this is the one.
[00:09:44.360 --> 00:09:46.280] You've always got to keep an open mind to that.
[00:09:46.600 --> 00:09:55.320] So 150 women aged between 18 and 45 who were struggling with either PMS or PMDD were recruited.
[00:09:55.320 --> 00:10:09.320] So PMS or pre-menstrual syndrome, as I'm sure listeners are aware, is a range of symptoms, typically including anxiety, depression, mood swings, breast tenderness, insomnia, which are commonly experienced in the run-up to menstruation.
[00:10:09.640 --> 00:10:12.440] PMDD, people might not be as familiar with.
[00:10:12.440 --> 00:10:17.320] This is pre-menstrual dysphoric disorder, which is PMS on steroids.
[00:10:17.320 --> 00:10:20.120] Not literally on steroids, but metaphorical steroids.
[00:10:20.280 --> 00:10:22.360] Not least because steroids might actually help some of the symptoms.
[00:10:23.800 --> 00:10:28.840] So it's PMS, but everything's dialed up to 11, which can be seriously debilitating.
[00:10:29.400 --> 00:10:33.240] It can be really, really serious, including suicidal ideation.
[00:10:33.640 --> 00:10:35.560] It can get that bad.
[00:10:36.200 --> 00:10:45.000] So, 150 women aged between 18 and 45 who suffer with either PMS or PMDD were recruited, and they were randomly assigned into one of three groups, right?
[00:10:46.160 --> 00:10:49.040] The first group was given open-label placebo.
[00:10:49.040 --> 00:10:53.440] So, it was two dummy pills that they would take every day for six weeks.
[00:10:53.760 --> 00:11:01.040] The placebos were, of course, accompanied by a treatment rationale, as is always the case in the open-label placebo studies.
[00:11:01.040 --> 00:11:04.320] They told the patients that placebo effects can be large.
[00:11:04.320 --> 00:11:04.800] Okay.
[00:11:04.800 --> 00:11:10.720] They told the patients placebo effects work without deception, even though that's what the study is trying to demonstrate.
[00:11:10.720 --> 00:11:11.920] Yeah, yeah, yeah, yeah.
[00:11:11.920 --> 00:11:14.880] They told them placebo effects work without deception.
[00:11:14.880 --> 00:11:18.720] They said placebos may decrease PMS symptoms.
[00:11:18.720 --> 00:11:21.600] May is doing a lot of heavy lifting in that sentence.
[00:11:21.600 --> 00:11:26.560] It's like it may do that, it may cause monkeys to spring out of your ass as well.
[00:11:26.560 --> 00:11:27.520] But probably won't.
[00:11:27.760 --> 00:11:28.480] Probably won't.
[00:11:28.480 --> 00:11:29.040] Yeah.
[00:11:29.360 --> 00:11:36.640] Placebo accounts for 40% of the improvements seen in PMS studies, was another thing that they were told.
[00:11:36.640 --> 00:11:39.440] Okay, so you're going to get better, and it's mostly because of this thing, anyway.
[00:11:39.680 --> 00:11:40.480] So you'll be fine.
[00:11:41.120 --> 00:11:52.480] And they were then shown an NBC news report, a historic NBC news report, about how brilliant placebos are, which was looking, I think, I haven't got this in my notes, but I think it was one of Ted Kapchuk's studies on IBS.
[00:11:52.720 --> 00:11:55.760] And it was a news report on that that they were shown.
[00:11:55.760 --> 00:11:57.120] Fucking Ted Kapchuck, man.
[00:11:57.120 --> 00:11:58.400] Jesus Christ.
[00:11:58.400 --> 00:12:04.000] Very, very much priming the audience to expect some sort of changes there, I would argue.
[00:12:04.160 --> 00:12:09.200] But also specifically priming them to get the thing that you're investigating.
[00:12:09.440 --> 00:12:11.200] You're actually looking for, yeah.
[00:12:11.200 --> 00:12:27.200] So I would argue that, like the noise in the night, this priming leads patients to notice small variations in their condition and report on those, even if those changes would have been so trivial that they would have gone unnoticed otherwise.
[00:12:27.520 --> 00:12:28.880] So, that's the first group, right?
[00:12:28.880 --> 00:12:30.680] Open label placebo with priming.
[00:12:30.680 --> 00:12:31.400] That's the first group.
[00:12:29.840 --> 00:12:35.400] The paper refers to this as the OLP plus group.
[00:12:36.360 --> 00:12:44.440] The second group gets the same placebo, the same dose, but doesn't get the priming, doesn't get the treatment rationale, right?
[00:12:44.440 --> 00:12:46.840] They refer to this as the OLP-minus group.
[00:12:46.840 --> 00:12:48.120] Makes sense.
[00:12:48.440 --> 00:12:52.680] And the final group, well, the final group's a bit odd.
[00:12:52.680 --> 00:12:56.520] The paper refers to this as the treatment-as-usual group.
[00:12:56.840 --> 00:13:11.640] But what actually this, what this amounts to actually is a no-treatment control, because no one in that group or in any group was taking anything for PMS and PMDD, which is not treatment as usual because people might be taking painkillers, for example.
[00:13:11.640 --> 00:13:15.640] Yeah, so the first-line therapy for PMS is typically SSRIs.
[00:13:15.640 --> 00:13:18.760] No one was taking SSRIs in this study, nobody was at all.
[00:13:18.760 --> 00:13:29.800] Some women were using hormonal contraceptives, which are used sometimes to manage PMS and PMDD, but we don't know that that's why they were taking them because they might have been taking them as a contraceptive.
[00:13:31.080 --> 00:13:40.040] It's unclear which one they were using it for, or indeed whether it was both, because quite often when you go to the doctor and they'll say, Oh, have you considered going on the pill?
[00:13:40.040 --> 00:13:44.920] Because it works as a contraceptive and it also will help stabilize you hormonally.
[00:13:45.560 --> 00:14:04.200] Some women were reported as taking paracetamol, some were taking ibuprofen, some were taking D-mannose, some were taking aspirin, some were on zinc, some were on antihistamines, some of them were taking folate, some were taking homeopathy, some were receiving acupuncture, some were having chronosacral therapy, some were taking treatment from an osteopath.
[00:14:04.200 --> 00:14:12.440] Because basically, this no treatment control, this treatment as usual group was whatever you were doing for whatever reason is fine.
[00:14:12.440 --> 00:14:15.760] And it's interesting that there's such a wide range of things, so there's 150 women.
[00:14:14.920 --> 00:14:16.320] 150 women.
[00:14:16.480 --> 00:14:27.040] And that's quite a wide range of things to come up, which also sort of nods towards the fact that there isn't a good treatment for this because medicine hasn't done a great deal of prioritizing of this as an issue.
[00:14:27.200 --> 00:14:28.320] Yeah, absolutely.
[00:14:28.320 --> 00:14:33.600] Were the two other treatment arms were people told to stop doing what they would typically do?
[00:14:33.600 --> 00:14:34.080] No.
[00:14:34.080 --> 00:14:41.760] Okay, so this was everyone could do this no matter what group they were in, they could keep taking paracetamol or stop or do whatever the fuck they wanted.
[00:14:42.080 --> 00:14:55.600] At such a small N number, you've not, unless they've done some very clever weighting, which I'm sure they haven't, and would be very, it would be near impossible to do with such a small group number.
[00:14:55.600 --> 00:15:09.840] Like, how do you know that you haven't got all your homeopathic treatments in group one, all your people taking De Manos in another group, and you know, you're actually testing one of the alternative therapies that these patients are taking?
[00:15:09.840 --> 00:15:15.200] Would that not have come out in the results afterwards if you were asking you would hope that they would list all of those things?
[00:15:16.240 --> 00:15:18.960] They do list them all and they list which women were taking them.
[00:15:18.960 --> 00:15:23.360] I don't recall if they said which groups they were in and whether there was a statistically significant.
[00:15:23.360 --> 00:15:24.960] I don't recall that analysis from the paper.
[00:15:24.960 --> 00:15:26.000] Maybe it's there and I missed it.
[00:15:26.080 --> 00:15:36.880] That feels like it would be a useful analysis because you say if all of the women who are taking a paracetamol are in the open label plus group, then what you might be discovering is the effects of paracetamol.
[00:15:37.760 --> 00:15:52.640] And you would hope that they try and evenly distribute them to some extent, but when you're distributing so many treatments plus, the demographics of those patients, there's not, you're not going to be able to do that differently, you're not randomizing that either.
[00:15:52.640 --> 00:15:54.720] Which, yeah, which makes it hard as well, right?
[00:15:54.720 --> 00:15:58.080] Because with your randomization, you want to randomize it.
[00:15:58.080 --> 00:16:10.600] You don't want to say that there are ways to randomize in a way that has some level of either weighting or you can statistically analyze that afterwards and take it out of the equation to some extent.
[00:16:10.920 --> 00:16:13.320] But I would say you need a much bigger number.
[00:16:13.320 --> 00:16:17.560] Obviously, there's a massive amount of background variation in the patients in this group.
[00:16:17.560 --> 00:16:18.760] Massive, a massive amount.
[00:16:18.760 --> 00:16:27.240] And I would personally say that it's misleading to call that a treatment as usual group, given that it was just keep doing whatever you're doing for whatever reason or stop whatever.
[00:16:27.640 --> 00:16:32.200] And some of those treatments likely aren't related to PMS and PMDD.
[00:16:32.200 --> 00:16:32.600] Yep.
[00:16:32.600 --> 00:16:33.800] But a lot of them would be.
[00:16:33.800 --> 00:16:37.160] Like D-manos, probably because they think they're getting UTIs.
[00:16:37.160 --> 00:16:38.840] UTI is typically for D-manos, yeah.
[00:16:38.840 --> 00:16:44.600] But that could be related to the bloating that they're struggling with around their period.
[00:16:44.600 --> 00:16:45.000] Yeah.
[00:16:45.320 --> 00:16:56.280] So this applied across all the groups, but no one was actually getting standard care for PMS, which says to me that there isn't really a standard care for PMS.
[00:16:56.440 --> 00:17:01.720] Yeah, so first-hand care is SSRIs, which to me sort of feels like we don't have anything good.
[00:17:01.720 --> 00:17:05.800] Maybe you're just a bit glum, have this and go away kind of thing.
[00:17:06.120 --> 00:17:10.600] But okay, I suppose in a sense, it is as usual in the sense that, you know, you carry on what you're doing.
[00:17:10.600 --> 00:17:20.920] But it's an important limitation to note that the placebo groups were on top of this very noisy background, not instead of this very noisy background.
[00:17:21.240 --> 00:17:22.040] So that's the study.
[00:17:22.040 --> 00:17:27.960] Yeah, placebo with rationale, placebo without rationale, and what they call treatment as usual.
[00:17:27.960 --> 00:17:30.440] And there were two primary outcome measures.
[00:17:30.440 --> 00:17:34.440] They were PMS symptom intensity and functional interference.
[00:17:34.440 --> 00:17:37.880] Both of these were recorded by patients filling out a symptom diary.
[00:17:37.880 --> 00:17:45.000] Yeah, which means, as you might infer from the names, a symptom diary is where you record the symptoms.
[00:17:45.200 --> 00:17:47.600] Symptom intensity is how severe they are.
[00:17:47.600 --> 00:17:51.280] Functional interference is how much it gets in the way of your day-to-day life.
[00:17:51.280 --> 00:17:51.920] Yeah.
[00:17:51.920 --> 00:17:56.080] And that's the only way you could record that because there isn't an objective measurement of those conditions.
[00:17:56.240 --> 00:17:57.200] Indeed, yeah.
[00:17:57.520 --> 00:17:59.840] There were also two secondary outcome measures.
[00:17:59.840 --> 00:18:09.280] These are psychological symptom intensity and somatic symptom intensity, which are actually subgroups of the primary outcome measure.
[00:18:09.280 --> 00:18:19.200] So they took the original symptom intensity data and split it down into psychological symptoms like mood swings, irritability, anxiety, and aggregated those as another analysis.
[00:18:19.200 --> 00:18:25.840] And then the physical symptoms like bloating, breast tenderness, headaches, and aggregated all of those into another group to analyze.
[00:18:27.600 --> 00:18:31.600] Which is reasonable and a reasonable breakdown to do.
[00:18:31.600 --> 00:18:37.920] I would like for them to have said before they did the study that they were going to do that rather than doing it after the fact.
[00:18:38.240 --> 00:18:40.800] They pre-registered the trial and said this is exactly how we're going to do the analysis.
[00:18:40.880 --> 00:18:42.000] In fairness to them, they do.
[00:18:42.000 --> 00:18:43.280] Okay, that's good.
[00:18:43.520 --> 00:18:53.440] And it is a reasonable enough disambiguation to make that you would expect if they were going to pre-register that they would pre-register that particular analysis.
[00:18:53.440 --> 00:18:55.600] And we'll touch on that a little bit more later.
[00:18:55.600 --> 00:19:00.080] I would argue these aren't true secondary measures because they're just a different way of looking at the primary data.
[00:19:00.080 --> 00:19:00.480] Yeah.
[00:19:00.480 --> 00:19:01.360] But okay, fair enough.
[00:19:01.360 --> 00:19:03.120] They're like two halves of the primary.
[00:19:03.120 --> 00:19:03.600] Yeah.
[00:19:03.920 --> 00:19:19.600] So the authors of this study conclude: so this is from the paper: administering open-label placebos with treatment rationale to women with PMS can decrease symptom intensity and interference considerably in the absence of substantial side effects with full transparency.
[00:19:19.600 --> 00:19:28.520] Considering our results, open-label placebo treatment could serve as an acceptable, efficacious, and safe intervention for PMS.
[00:19:28.160 --> 00:19:32.040] And that's such a frustrating conclusion.
[00:19:32.360 --> 00:19:43.880] I'm sure you're going to go into why it doesn't hold up, but it's a frustrating conclusion because you're already talking about something where there isn't sufficient medicalized priority to actually get something that works.
[00:19:43.880 --> 00:19:44.760] Oh, it's just women.
[00:19:44.760 --> 00:19:45.640] This happens every month.
[00:19:45.640 --> 00:19:47.000] We shouldn't worry about it, etc.
[00:19:47.240 --> 00:19:53.880] Those kind of paternalistic dismissals that drive people to go looking and seeking other treatments because they haven't got a treatment.
[00:19:53.880 --> 00:19:57.640] And now they're saying this thing that we don't have a good treatment for, it's fine.
[00:19:57.640 --> 00:19:59.560] We figured out we can give them nothing.
[00:19:59.560 --> 00:20:00.440] How empowering.
[00:20:01.480 --> 00:20:10.280] It's only more recently that we've even started to have the conversation that maybe we don't just have to put up with PMS because it's a normal part of having a period.
[00:20:10.280 --> 00:20:20.120] Likewise, painful periods have only just been part of the conversation more recently that people are recognizing that we don't just have to put up with really painful periods.
[00:20:20.120 --> 00:20:22.520] And actually, really painful periods isn't normal.
[00:20:22.520 --> 00:20:24.120] It's common, but it isn't normal.
[00:20:24.120 --> 00:20:26.600] It isn't something that you need to just live with.
[00:20:26.920 --> 00:20:32.840] So going through the raw results, there are many, many, many comparisons made in this study.
[00:20:32.840 --> 00:20:45.400] They do a comparison from baseline to OLP minus at the midpoint, from baseline to OLP minus at the end point, from baseline to OLP plus at the midpoint, from baseline to OLP plus at the end point.
[00:20:45.400 --> 00:20:49.800] For each of these, they look at symptom intensity and the functional interference scores.
[00:20:49.800 --> 00:20:55.400] And then again, for the psychological version of the intensity and the somatic version of the intensity.
[00:20:55.400 --> 00:20:58.360] So many different ways that they've carved this data up and analyzed.
[00:20:59.160 --> 00:21:10.640] The first set you were talking about there would make sense that you're doing the plus, the minus, the no treatment at midpoint and end point, but then you're doing so many different analyses at each midpoint and each endpoint for each arm.
[00:21:10.440 --> 00:21:10.800] Yeah.
[00:21:11.320 --> 00:21:18.960] But I was very happy to see that the authors of this paper have remarkably, because we see this so infrequently, adjusted for multiple comparisons.
[00:21:14.840 --> 00:21:19.280] Oh, no.
[00:21:19.520 --> 00:21:26.080] This is the first time I think I've seen a placebo paper where they have gone out and done the adjustment for multiple comparisons.
[00:21:26.080 --> 00:21:30.000] And when they did that, almost all of their significant findings disappeared.
[00:21:30.560 --> 00:21:36.960] They still report on them in the paper and say, we found this, we found this, we found this, even though they were not significant.
[00:21:36.960 --> 00:21:37.440] Wow.
[00:21:37.440 --> 00:21:41.200] So because individually they were significant before they did the multiple comparison.
[00:21:41.200 --> 00:21:41.440] Yeah.
[00:21:41.440 --> 00:21:42.400] And these were significant.
[00:21:42.400 --> 00:21:44.960] And also we did the multiple comparison thing, so we've done things the right way.
[00:21:44.960 --> 00:21:46.080] Is that essentially it?
[00:21:46.080 --> 00:21:46.640] Yeah.
[00:21:46.640 --> 00:21:53.760] So the paper still reports on several of the non-significant findings as if they were significant in the paper.
[00:21:53.760 --> 00:22:00.080] In fact, after adjustment, there are no significant findings at all for the open label placebo without rationale.
[00:22:00.080 --> 00:22:01.280] So without the priming.
[00:22:01.680 --> 00:22:08.880] Absolutely zero significant findings for that, either the midpoint, the end point, the somatic symptoms, the overall, none of it, nothing at all.
[00:22:08.880 --> 00:22:13.760] The only significant effect which remained was for the open label placebo with rationale.
[00:22:13.760 --> 00:22:17.760] And in many cases, even these were not very deep into significance.
[00:22:17.760 --> 00:22:22.480] They were like a p-value of 0.03, 0.04, that kind of thing.
[00:22:22.720 --> 00:22:27.520] Some of them were south of 0.01, but not an awful lot of them.
[00:22:27.840 --> 00:22:31.760] Now, as we've discussed, some of these outcome measures were derivative.
[00:22:31.760 --> 00:22:39.040] So if one outcome is significant, it's not really a surprise that measurements derived from that outcome will also be significant.
[00:22:39.280 --> 00:22:43.600] So the so-called secondary outcome doesn't really add very much to the study.
[00:22:43.600 --> 00:22:50.720] And I'd rather get the impression that they added these to the trial registration, assuming they wouldn't find anything.
[00:22:50.720 --> 00:22:56.880] And so saying, oh, and we're going to give ourselves the opportunity to carve up the data in several different ways later as well.
[00:22:57.200 --> 00:22:58.000] Yeah, it could be.
[00:22:58.000 --> 00:23:07.080] I don't know that that's the case, but I can so totally see a version of this paper where the primary outcome found nothing, but they said, Oh, but if you look at just the somatic symptoms, it turns out it's brilliant.
[00:23:07.320 --> 00:23:08.200] Yeah, yeah.
[00:23:08.520 --> 00:23:18.440] But that isn't what ended up happening, so the secondary measure ends up being somewhat redundant because they say overall it improves it and improves psychologically and improves somatic symptoms.
[00:23:18.520 --> 00:23:23.800] But it's perfectly reasonable to separate those out, especially on a study looking at placebo specifically.
[00:23:23.800 --> 00:23:24.200] It is, yeah.
[00:23:24.440 --> 00:23:30.280] But it's like he ran the first he ran the 100 meters quickly, and of that he ran the first 50 meters quickly and the second meters.
[00:23:30.360 --> 00:23:31.640] And the second meters quickly.
[00:23:31.640 --> 00:23:34.360] I mean, in fairness, it could have been all was in the psychological thing.
[00:23:34.600 --> 00:23:34.840] That's true.
[00:23:35.720 --> 00:23:39.160] But yeah, it just means that secondary outcome measure was largely redundant here.
[00:23:39.160 --> 00:23:47.960] But anyway, as is commonly the case when we look at placebo effect research, we have another study here which is based entirely on self-reported data.
[00:23:47.960 --> 00:23:54.600] So I would argue that the findings here are not really different to what you would expect to see if the placebo effect does not exist.
[00:23:54.600 --> 00:24:04.280] If the placebo effect is N-rays, we would still expect to see this same data, these same findings, because you've said it's going to help you.
[00:24:04.280 --> 00:24:07.800] And so any opportunity you have to say, do I feel a little bit better?
[00:24:07.800 --> 00:24:09.080] I think I probably do.
[00:24:09.080 --> 00:24:10.040] You're going to record.
[00:24:10.280 --> 00:24:12.760] Well, you're not going to, but you're more likely to.
[00:24:12.760 --> 00:24:13.160] To record it.
[00:24:13.400 --> 00:24:17.560] It probably takes that more likelihood for it to triple to start pushing things in that direction.
[00:24:17.560 --> 00:24:22.360] This isn't the brain activating some mysterious mind-body healing process.
[00:24:22.360 --> 00:24:28.920] These results can be fully accounted for by reporting bias introduced through priming.
[00:24:29.240 --> 00:24:31.800] It's not evidence of a therapeutic effect.
[00:24:31.800 --> 00:24:35.640] It's a textbook example of psychological manipulation.
[00:24:35.640 --> 00:24:46.560] In fact, it's a psychological manipulation with a major confounder, which is there's no blinding, but they've dressed that up as a desirable aspect of this study.
[00:24:47.440 --> 00:24:54.480] Demonstrating that priming and confirmation bias are a thing, which is all this study is doing, I think, doesn't really achieve anything.
[00:24:55.360 --> 00:24:59.360] There's plenty of evidence that these effects exist, they're well known, they're recorded in the literature.
[00:24:59.360 --> 00:25:07.600] People like Chris French have made entire careers on how psychological biases can impact us in unexpected ways.
[00:25:07.600 --> 00:25:14.160] And just telling somebody that a house is haunted is enough to make them report having strange experiences in that house.
[00:25:14.160 --> 00:25:22.400] And having someone in authority tell you this medicine will help is going to make you more likely to say that it has, even if nothing has changed.
[00:25:22.400 --> 00:25:23.680] That's not healing.
[00:25:23.680 --> 00:25:24.640] That's not healthcare.
[00:25:24.640 --> 00:25:24.800] Yes.
[00:25:25.520 --> 00:25:35.280] That's not why people go to the doctor to have them bamboozle you into saying you feel better regardless of any objective improvement in your condition.
[00:25:35.600 --> 00:25:48.160] It's certainly not enough to justify recommending placebos as a first-line treatment as this paper does, especially not to women who already spend far too much of their lives being told that their suffering is all in their heads.
[00:25:52.000 --> 00:25:55.440] So me and Alice have recently got back from Barcelona.
[00:25:55.440 --> 00:25:55.840] Good.
[00:25:55.840 --> 00:25:59.040] Yeah, we went off to Barcelona with the Skeptics in the Pub Online team.
[00:25:59.040 --> 00:26:00.160] We did this a couple of years ago.
[00:26:00.160 --> 00:26:02.480] So the Skeptics in the Pub Online team were fantastic.
[00:26:02.480 --> 00:26:13.200] And we met up for drinks in Munich when Igor from the team, anybody who's watched a Skeptics in the Pub Online broadcast, will know Igor because he asked all the questions and they're excellent questions.
[00:26:13.280 --> 00:26:14.400] He just asked questions.
[00:26:15.040 --> 00:26:23.760] So when Igor had managed to leave Russia, we all went to Munich to hang out with Igor and drink to him and Nadia and celebrate and everything.
[00:26:23.760 --> 00:26:28.240] And then we went back to Germany the next year, went to Clorn for Gerald's birthday, which was Gerald's 50th.
[00:26:28.320 --> 00:26:29.200] So we all went to London.
[00:26:29.520 --> 00:26:30.120] Big celebration.
[00:26:30.360 --> 00:26:32.840] We didn't get to go away last year, so we got away this year.
[00:26:32.840 --> 00:26:34.040] Was it last you went to Clorn?
[00:26:34.040 --> 00:26:35.320] Fuck me, my brain is useless.
[00:26:29.920 --> 00:26:36.280] I think it was last year.
[00:26:36.920 --> 00:26:38.920] This year, we went to Barcelona.
[00:26:38.920 --> 00:26:40.680] I can't tell you about it because we haven't been there.
[00:26:40.680 --> 00:26:41.880] We're recording this slightly.
[00:26:41.880 --> 00:26:45.960] But it's nice to get to see all of the people from Skeptics.
[00:26:45.960 --> 00:26:56.200] But I think the people going is going to be Kat and Igor and Joe and David Glass and Dave Jenkins and me and you and Brian.
[00:26:56.200 --> 00:26:57.000] Yeah, yeah.
[00:26:57.000 --> 00:26:58.840] I think that's brilliant.
[00:26:59.640 --> 00:27:00.600] Fantastic.
[00:27:00.600 --> 00:27:02.760] Oh, you're mean.
[00:27:04.360 --> 00:27:06.600] There is a planet Barcelona in Doctor Who.
[00:27:06.600 --> 00:27:06.920] Is there?
[00:27:06.920 --> 00:27:07.320] Yeah.
[00:27:07.320 --> 00:27:11.080] The doctor at one point says they're going to take you to Barcelona, but not the city, to the planet.
[00:27:11.240 --> 00:27:14.840] Was that just so you could keep up the average of saying Doctor Who on more than half a day?
[00:27:17.400 --> 00:27:19.080] I've got to try and work a little more often.
[00:27:19.400 --> 00:27:28.280] What thing is, I've got a major confounder there of every time I say Doctor Who said this, that comes up as a false positive on the Doctor Who thing.
[00:27:28.280 --> 00:27:29.400] So I need to work double hard.
[00:27:29.480 --> 00:27:31.640] It catches me every time with newspaper headlines as well.
[00:27:31.640 --> 00:27:34.440] And it goes, you know, Doctor Who murdered patients.
[00:27:34.440 --> 00:27:35.320] I go, he fucking did.
[00:27:35.560 --> 00:27:36.600] I know, I do that every time.
[00:27:36.600 --> 00:27:37.080] That's great.
[00:27:37.080 --> 00:27:37.480] That's great.
[00:27:37.480 --> 00:27:39.160] I do it to Liberty every single time.
[00:27:39.480 --> 00:27:40.120] Wow.
[00:27:40.120 --> 00:27:41.640] God, he gets about.
[00:27:41.960 --> 00:27:44.360] But no, I'm glad that Barcelona went well.
[00:27:44.760 --> 00:27:46.360] That sounds like it was a wee.
[00:27:46.440 --> 00:27:48.040] I'm sure it will have been.
[00:27:52.200 --> 00:27:53.800] So, Liverpool Skeptics at the Pub.
[00:27:53.800 --> 00:27:56.440] We have an event this evening in Dr.
[00:27:56.440 --> 00:27:57.320] Duncan's on St.
[00:27:57.320 --> 00:27:57.880] John's Lane.
[00:27:57.880 --> 00:27:59.960] And if you're in the Liverpool area, you should definitely come along to that.
[00:27:59.960 --> 00:28:01.320] That's from 8 p.m.
[00:28:01.480 --> 00:28:03.000] Meet Mike, meet the rest of the board.
[00:28:03.000 --> 00:28:04.520] Me and Alice are going to be away.
[00:28:04.520 --> 00:28:06.440] Well, we are currently away as this goes out.
[00:28:06.440 --> 00:28:07.800] But that's a fantastic time.
[00:28:07.800 --> 00:28:11.160] You know, we get together, we have drinks, we tell stories, we have some jokes.
[00:28:11.320 --> 00:28:11.880] It's a fantastic thing.
[00:28:12.200 --> 00:28:12.760] Socials are great.
[00:28:13.240 --> 00:28:14.120] They're really good fun.
[00:28:14.120 --> 00:28:14.960] It's an awesome time.
[00:28:14.960 --> 00:28:17.760] You should definitely come along to that if you were in the Liverpool area.
[00:28:14.680 --> 00:28:21.120] Also, QED, we've got tickets for QEDs are still on sale.
[00:28:21.680 --> 00:28:29.840] You can pick yours up for £179 new British pounds from the website qedcon.org, the exclusive distributor of tickets for QED.
[00:28:30.160 --> 00:28:31.440] We managed to get the rights for it again.
[00:28:31.680 --> 00:28:32.400] We somehow.
[00:28:32.880 --> 00:28:34.160] We wanted to get held up.
[00:28:34.160 --> 00:28:36.000] We've got outbid Ticketmaster on it.
[00:28:36.000 --> 00:28:37.760] How we manage that, I don't know.
[00:28:38.240 --> 00:28:39.600] You do have to be careful.
[00:28:40.000 --> 00:28:45.680] If ever we tweet, well, actually, Twitter's just fucked and broken now, so I don't think it's the case anymore.
[00:28:45.680 --> 00:28:54.000] But it used to be that if you tweeted, whenever I tweeted on Twitter that we'd sold out the dinner, you'd get loads of bots going, like, I've got tickets for this thing.
[00:28:54.000 --> 00:28:54.640] Yeah, that's right.
[00:28:55.360 --> 00:28:56.480] You can get extra spare ones.
[00:28:56.480 --> 00:28:57.120] Yeah, that was great.
[00:28:57.360 --> 00:28:59.040] Yeah, it's not how that fucking works.
[00:28:59.040 --> 00:29:04.320] So, yeah, QED is on the 25th and 26th of October at the Mercure Piccadilly Hotel in Manchester.
[00:29:04.320 --> 00:29:07.600] There's going to be a Skepticamp event that is free for everyone to attend.
[00:29:07.600 --> 00:29:09.520] You don't need a QED ticket to come along.
[00:29:09.520 --> 00:29:17.280] So if you can't come to QED itself, maybe you're busy that weekend, you can still come to Skepticamp on the Friday and say hello and meet the team.
[00:29:17.280 --> 00:29:18.480] And that's going to be a fantastic time.
[00:29:18.480 --> 00:29:24.000] Skepticamp this year being run for us once again by the fantastic folks at Skeptics in the Pob Online, which is brilliant.
[00:29:24.000 --> 00:29:25.680] David does a fantastic job.
[00:29:25.680 --> 00:29:31.760] And so we're going to be, and the rest of the team, like you know, Malcolm and Gerald and things.
[00:29:31.760 --> 00:29:33.600] So we're doing really well on that.
[00:29:33.760 --> 00:29:35.600] You should come along to that if you're in the Liverpool area.
[00:29:35.600 --> 00:29:36.800] That's on the 24th.
[00:29:36.800 --> 00:29:40.320] And almost certainly, Manchester area, rather, that's going to be on the 24th.
[00:29:40.320 --> 00:29:42.560] And almost certainly it's going to be stuff going on on the Thursday as well.
[00:29:42.640 --> 00:29:43.680] It's going to be great.
[00:29:44.000 --> 00:29:56.000] Also, if you enjoy the show and you like what we do, and you would like to support us and the time and effort that we put into this show, you could do that by joining our Patreon, which is a patreon.com forward slash skeptics with a K.
[00:29:56.000 --> 00:29:58.880] In exchange for that, you get an ad-free version of this show.
[00:29:58.960 --> 00:30:05.640] You do so without any leading advertising, it is really very much the best way to support us, and that's definitely the way that you should be going.
[00:30:05.800 --> 00:30:12.600] And we've got some people saying, I feel like I should just listen to the ads because then that's how much more entertaining than the ad-free show.
[00:30:13.240 --> 00:30:15.400] No, definitely the Patreon's a much better way to do it than that.
[00:30:15.560 --> 00:30:19.240] Throwing us a couple of quid a month, we'll do far far more than the ads.
[00:30:19.240 --> 00:30:21.080] Yeah, so it's very, very cheap to sign up.
[00:30:21.080 --> 00:30:23.800] We're not trying to upsell you and all that sort of stuff.
[00:30:23.800 --> 00:30:26.520] It really does help us out and help us keep the show going.
[00:30:26.520 --> 00:30:37.640] Also, if you like what we do with the show and what we do at Merseyside Skeptics, you can support Mercy Side Skeptics by going to their Patreon, which is patron.com forward slash Mercy Skeptics, where you will also get an ad-free version of this show.
[00:30:37.640 --> 00:30:40.920] Yeah, aside from that, then I think that is all we've got time for.
[00:30:40.920 --> 00:30:41.960] I think it is.
[00:30:41.960 --> 00:30:44.680] All that remains then is for me to thank Marsh for coming along today.
[00:30:44.680 --> 00:30:45.240] Cheers.
[00:30:45.240 --> 00:30:46.200] Thank you to Alice.
[00:30:46.200 --> 00:30:46.760] Thank you.
[00:30:46.760 --> 00:30:49.320] We have been Skeptics with a K, and we will see you next time.
[00:30:49.320 --> 00:30:50.040] Bye now.
[00:30:50.040 --> 00:30:51.000] Bye.
[00:30:55.800 --> 00:31:00.840] Skeptics with a K is produced by Skeptic Media in association with the Merseyside Skeptic Society.
[00:31:00.840 --> 00:31:09.880] For questions or comments, email podcast at skepticswithakay.org, and you can find out more about Merseyside Skeptics at mercysideskeptics.org.uk.