The Fault Lies in Our Stars

December, 13, 2020 | 7 Comments


  1. This links in my opinion into issues Jean-François has raised that I have not addressed here but hope to in my book Shipwreck of the Singular when it comes out. Neo-liberalism is essentially one-dimensional. It substitutes operational procedures for judgement. Having said this, it may now be clear to some that my essay (the revised one more obviously) is as much about neo-liberalism as it is about clinical trials.

    David Healy September 28th

    Prof. Peter Gøtzsche

    Fawlty Stars**

    Casting RCTs as offering gold standard evidence about a drug creates an ignorance about the ignorance they generate.*very good point*

    In the case of airplanes, adding parachutes and other interventions that are effective (rather than just have an effect) enhances safety, although recent Boeing plane crashes point to the perils of too great a reliance on automatic decision tools. *Please drop this. Airlines are very safe, much safer than any other means of transport*

    In March 2019, the Boeing 737 MAX passenger airliner was grounded worldwide after 346 people died in two crashes, Lion Air Flight 610 on October 29, 2018 and Ethiopian Airlines Flight 302 on March 10, 2019. Ethiopian Airlines immediately grounded its remaining MAX fleet.

    Cause: Airworthiness revoked after recurring flight control failure

    Date: Lion Air accident: October 29, 2018, Ethiopian Airlines accident: March 10, 2019,
    First grounding: March 10, 2019 by Ethiopian Airlines,
    First nationwide grounding: March 11, 2019 by the Civil Aviation Administration of China (CAAC),
    Effectively a worldwide grounding: March 13, 2019 by the Federal Aviation Administration (FAA), Cleared for return to service: November 18, 2020 by the FAA

    Deaths: 346:, 189 on Lion Air Flight 610, 157 on Ethiopian Airlines Flight 302

    Duration: between accidents: 4 months and 10 days, of grounding by the FAA: 1 year, 8 months and 5 days (619 days)

    Boeing’s safety analysis of the system assumed that “the pilots would recognize what was happening as a runaway and cut off the switches,” said the engineer. “The assumptions in here are incorrect. The human factors were not properly evaluated.”

    Flawed analysis, failed oversight: How Boeing, FAA certified the suspect 737 MAX flight control system

    Peter Lemme, a former Boeing flight controls engineer who is now an avionics and satellite-communications consultant, said that because MCAS reset each time it was used, “it effectively has unlimited authority.”

    Facing legal actions brought by the families of those killed, Boeing will have to explain why those fixes were not part of the original system design. And the FAA will have to defend its certification of the system as safe.

    Boeing 737 MAX Plane, is, in my opinion, the perfect analogy

    Fresh from the Cockpit –
    “This is the Captain speaking”

    Patrick D Hahn

    SmithKline’s own studies showed nearly seven times as many suicide attempts per patient on #Paxil compared to #placebo.

    Healthcare’s Castaways and GSK Paroxetine, take note…

  2. There is so much to think about here, For now I found this article helpful RCTs seem to hark back to the Victorian obssession with classification initially with plants but has contaminated the thinking about people The classification was fairly harmless when we could all recognise some one as say introvert or extravert, but with greater and greater use of technology the perception of a person has become more and more dehumanising, More and more classification has become an insult to those on the receiving end of a ‘consultation.; Some aspects of RCTs can seem ridiculous , using little more than guesses in scientific garb eg confidence levels.-
    But It seems that RCTs do have a use along with other methods for research I would be doubtful though about relying on the morality of groups of clinicians getting together to investigate ‘cases’ without some sort of oversight As soon as groups develop the same old corrupt behaviour is likely Case reports can be skewed. How could a ‘patient’ be able to have an independant input to verify or contribute equally to what is being documented?

    American Psychological Association LogoSearch Menu
    Home//Monitor on Psychology//2010//09//

    More than one way to measure
    Randomized clinical trials have their place, but critics argue that researchers would get better results if they also embraced other methodologies.

    By Rebecca A. Clay

    September 2010, Vol 41, No. 8

    Print version: page 52

    6 min read

    Ben A. Williams, PhD, came by his distrust of randomized controlled trials (RCTs) the hard way: He developed a kind of brain cancer with no proven treatment.

    There had been randomized trials of various approaches, but they were all failures, says Williams, an emeritus psychology professor at the University of California at San Diego. And although several drugs had helped a small percentage of patients in Phase II trials, he says, it can be hard to get hold of therapies not yet vetted by Phase III trials.

    “Medicine was basically saying if it isn’t done this way, it doesn’t count,” says Williams, describing the difficulties his physicians had in gaining access to therapies that probably wouldn’t help him, but might. “The problem is the one-size-fits-all mentality.”

    Like Williams, many other psychologists — as well as medical researchers — question the assumption by the National Institutes of Health, the Food and Drug Administration and others that RCTs should be the gold standard for clinical research. While the methodology — which involves randomly assigning participants to either a treatment or control group — does have its strengths, they say, it also has serious limitations that are often overlooked or ignored.

    Because trial participants typically don’t represent the population as a whole, for example, results from RCTs may not apply more generally. And even if they did, it’s impossible to tell from an RCT which subset of participants actually benefited from the intervention being studied.

    These critics don’t want to reject RCTs altogether. Rather, they want to supplement their findings with evidence from other methodologies, such as epidemiological studies, single-case experiments, the use of historical controls or just plain clinical experience.

    Strengths and weaknesses

    No one denies that RCTs have their strengths.

    “Randomized trials do two things that are very rare among other designs,” says William R. Shadish, PhD, a professor of psychological science at the University of California at Merced. “They yield an estimate of the effect that is unbiased and consistent.” Although Shadish is reluctant to describe RTCs as the gold standard because the phrase connotes perfection, he does describe himself as a “huge fan” of the methodology.

    “If you can do a randomized trial,” he says, “by all means do it.”
    But that’s not always possible. By their very nature, he says, some questions don’t permit random assignment of participants. Doing so might be unethical, for example.

    Even when RCTs are feasible, they may not provide the answers researchers are looking for.

    “All RCTs do is show that what you’re dealing with is not snake oil,” says Williams. “They don’t tell you the critical information you need, which is which patients are going to benefit from the treatment.”

    To account for heterogeneity among participants, he explains, RCTs must be quite large to achieve statistical significance. What researchers end up with, he says, is the “central tendencies” of a very large number of people — a measure that’s “not going to be representative of much of anybody if you look at them as individuals.”

    Move beyond the context of an RCT itself, and the applicability of the results to individual patients becomes even more problematic.

    For one thing, participants in RCTs tend to be a “pretty rarefied population” that isn’t representative of the real-world population an intervention would eventually target, says Steven J. Breckler, PhD, executive director of APA’s Science Directorate.

    “Think about the people who show up for drug trials — patients who have probably tried everything else and are desperate for some kind of treatment,” he says, adding that they are further winnowed down as researchers eliminate would-be participants with co-morbid conditions and the like. “Are the results of that trial going to generalize to you and me? Or do we come from a population of people who would never have enrolled in a trial to begin with?”

    Experiments, says Breckler, typically involve a trade-off between internal validity — the ability to trace causal inferences to the intervention — and external validity — the generalizability of the results.

    “What people seem to fail to recognize is that the perfect RCT is designed strictly with internal validity in mind,” he says.

    RCTs may be especially ill-suited to psychological interventions versus medical ones, adds Breckler. In contrast to medications that have a straightforward biochemical effect that’s unlikely to vary across individuals, he says, psychological interventions tend to interact with such factors as gender, age and educational level.

    Supplementing RCTs

    No one suggests that researchers give up RCTs. Instead, they urge the supplementation of RCTs with other forms of evidence.

    “Evidence-based practice should rely on a very broad, diverse base of evidence,” says Breckler. “RCTs would be one source, but there are lots of other sources.” These sources could include Phase II trial data, epidemiological data, qualitative data and reports from the field from clinicians using an intervention, say Breckler and others.

    Williams champions the use of historical controls as a supplemental source of information.

    In this methodology, researchers examine the results of earlier, nonrandomized trials to establish a crude baseline. They then compare the results of subsequent nonrandomized trials to that benchmark.

    The approach works, says Williams, adding that the process allows many interventions to be tested in quick succession. Faced with the failures of RCTs for glioblastoma treatment, for example, researchers turned to the historical record and found that only 15 percent of those with the cancer had no disease progression six months after treatment began.

    “They found that if you add this thing to the standard treatment, you can push that number up to 25 percent and add two things and push it up to 35 percent,” he says. “It’s a crude comparison, no doubt, but it turns out to be an effective way of doing the research.”

    The FDA agreed, approving a drug for treatment of glioblastoma not on the basis of an RCT but on multiple Phase II trials whose results were better than the historical norm.

    Single-case experiments are another important source of evidence, says Alan E. Kazdin, PhD, a past president of APA and professor of psychology and child psychiatry at Yale. In contrast to RCTs, which involve many subjects and few observations, single-case designs involve many observations but often few subjects. Instead of simply doing a pre- and postassessment, the researcher assesses behavior — of an individual, a classroom, even an entire school — over time.

    Say a patient has a tic, says Kazdin. In a single-case design, the researcher would observe the patient and establish the number of tics per hour. The researcher would then conduct an intervention and watch what happens over time.

    “If you just do an assessment before some treatment and an assessment after treatment and compare the group that got it to the group that did not, you lose the richness of the change on a day-to-day, week-to-week, month-to-month basis,” says Kazdin, emphasizing that single-case designs are not mere case studies.

    For Kazdin, overreliance on RCTs means missing out on all sorts of valuable information. Think of the nation’s telescope program, he says. The Hubble telescope looks at visible light. Another telescope looks at X-rays. Another handles gamma rays.

    “The method that you use to study something can influence the results you get,” says Kazdin. “Because of that, you always want to use as many different methods as you can.” *

    Rebecca A. Clay is a writer in Washington, D.C.

    Further reading
    Kazdin, A.E. (2010). Single-Case Research Designs: Methods for Clinical and Applied Settings, 2nd edition. New York: Oxford University Press.Shadish, W.R., Clark, M.H., & Steiner, P.M. (2008). Can nonrandomized experiments yield accurate answers? A randomized experiment comparing random and nonrandom assignments. Journal of the American Statistical Association, 103, 484, 1334–1356.Shadish, W.R., Cook, T.D., & Campbell, D.T. (2001). Experimental and Quasi-Experimental Designs for Generalized Causal Inference, 2nd ed. Florence, KY: Wadsworth.Williams, B.A. (2010). Perils of evidence-based medicine. Perspectives on Biology and Medicine, 53, 1, 106–120.

  3. Thanks David, for this article.

    RCTs can be a valuable and important research instrument, but they are not necessarily the only and not always the best way to conduct research, especially not in mental health research.

    The correct interpretation of RCTs requires very careful consideration. To determine if other forms of research may be more appropriate and yield more.

    In part 1 “the right size” of a presentation I gave, entitled “Tapering medication (tapering strips) as a necessary tool for a meaningful conversation in the doctors office” I have tried to make this clear using an RCT involving clogs for medical personel as an analogy.

    The presentation can be viewed here:

    Peter Groot,
    User Research Centre NL
    University Medical Center Utrecht

  4. UK Psychiatrists are ripping people off neuroleptics- who have been on for more than a year – in two weeks. This happened to me – 400mg quetiapine ordered by phone to come off in two weeks and they contacted my GP to order him – no more tablets ofter two weeks. They don’t give a damn about correct slow taper.

    • Good grief Chris, this is so frightening. I am surprised that you have lived to tell the tale. My son was on 400mg of Quetiapine daily – took him over three years of sheer hell to reduce it to 125mg daily, which is where he remains at present.

      • Sorry my mistake it was 100mg. I wish I had recorded the phone call. Wasn’t going to say no to comming off that vile drug. Lucky that I had a large quantity of 25mg tablets to tapper off over three months.

        The general public have no idea where all this virus business is going but they are worried by design. The technocracy madness wants to replace money with energy and social scientists (psychologists/psychiatrists) replacing left right politics to control us all, and what do you know – SAGE are social scientists.

        “Cameron’s presidential address to the American Psychiatric Association in 1953 suggests his involvement in the Cold War and his concerns about communism. Although he also used the opportunity to express his concerns about McCarthyism, Cameron held to a now familiar position — our best hope for a new world order and without hysteria, one without the totalitarianism of either the right or left, lies in science. With behavioural scientists as leaders, order would emerge from chaos. Were these attitudes a factor in his determination to change behaviour? It seems likely.”

        “our best hope for a new world order and without hysteria, one without the totalitarianism of either the right or left, lies in science. With behavioural scientists as leaders, order would emerge from chaos.”

        Donald Ewen Cameron torturer

        Could this be a start to fight back:

        All the best to your son, I’ve had more than a taste of what he – and yourself – have been through.

  5. In his letter to the MHRA, Mr Osborne said: ‘It was quite apparent from the evidence that she had a psychotic reaction as a result of taking the drug [doxycycline] and yet there is nothing on the drug information leaflet that either highlights or mentions this possibility. The information sent out with the drug should be reviewed to prevent future deaths.’

    The MHRA is now probing the drug’s safety.

    Why common antibiotics may trigger mental breakdowns: Coroner ruled that a malaria drug could be to blame for this student’s death… and there’s worrying evidence hers is not an isolated case


    PUBLISHED: 01:29, 29 December 2020 | UPDATED: 02:39, 29 December 2020

    In the meantime, could many more patients be suffering, not realising it may be due to their antibiotics? Disturbing research suggests this may be the case.

    Scientists at Augusta University in Georgia, U.S., carried out one of the largest studies into the psychiatric side-effects of antibiotics such as doxycycline.

    They trawled through eight years’ worth of data from the U.S. Food and Drink Administration’s Adverse Event Reporting System — a catalogue of potentially harmful drug reactions reported by doctors and patients.

    Professor David Healy, a psychiatrist who was consulted in the Alana Cutland case, first raised concerns about potential harmful effects of doxycycline in 2013, when he was a professor of psychiatry at Bangor University.

    Now based at McMaster University in Ontario, Canada, Professor Healy says: ‘I know four or five people personally who have been on doxycycline and felt very anxious as a result. In all cases, the symptoms disappeared as soon as they stopped taking it.

    ‘In Alana Cutland’s case, it was an extreme effect. Most doctors think doxycycline is benign, but it may simply be the wrong drug for some people. The drug should carry a carefully worded warning to let people know the risks and that they should stop taking it immediately if they experience a mental health problem. It could save lives.’

    Citizen Science …

    The medical breakthroughs helped by ordinary people. This week: Clinical trials

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