Showing posts with label bias. Show all posts
Showing posts with label bias. Show all posts

Wednesday, 19 June 2019

Mindfulness for ADHD systematically reviewed

"According to presented descriptive results, all the studies (100%) showed improvement of ADHD [attention-deficit hyperactivity disorder] symptoms."

That was the standout sentence derived from the findings reported by Hélène Poissant and colleagues [1] who looked at "the available literature concerning MBIs [mindfulness-based interventions] in adult participants with ADHD." Mindfulness by the way, is described as a way of "reconnecting with our bodies and the sensations they experience" with a specific focus on "an awareness of our thoughts and feelings as they happen moment to moment." I'm no expert on mindfulness or mindfulness-based interventions but, from what I gather, the core of such intervention(s) is based around "somatically focused meditative techniques (body scan, sitting meditation, and mindful yoga) that are thought to help participants cultivate nonjudgmental, mindful awareness of present-moment experience." 'Focusing in on the present' seems to be the phrase that springs to mind.

Poissant et al examined the relevant peer-reviewed science on the application of the MBIs to ADHD upto June 2018. They specifically focused on adults with ADHD, and were able to track down "13 studies conducted with 753 adults (mean age of 35.1 years)" for inclusion in their systematic review. They observed that: "All the studies (100%) showed improvement of ADHD symptoms following an MBI." They also mentioned that: "mindfulness meditation training improves some aspects of executive function and emotion dysregulation" as per the findings of some of those studies.

Despite the '100% of studies showing improvement in ADHD symptoms' sentiments, I'm not falling hook, line and sinker for the value of MBIs in relation to ADHD. The main reason is the high risk of bias identified in quite a few of the studies reviewed by Poissant, related to things like performance bias ("blinding of participants and of personnel") and selection bias ("allocation concealment" and "selection bias"). One could argue that the examination of something like MBIs under research conditions is never going to be perfect. Unlike scientific investigation of a medicine, where a placebo can be formulated to look, smell and taste the same, it would be difficult to come up with something to approximate MBI and indeed, approximate what the 'active ingredient' of mindfulness actually is. Similar issues have been talked about on other occasions on this blog (see here).

That all being said, there is something appealing about MBIs both in terms of effect and also the fact that it can be learned by pretty much anyone, is cost-free and probably about as side-effect free as one could get. If such a simple technique helps with any one of the symptoms of ADHD and improves quality of life for those with ADHD, it's got to be something to be considered alongside the myriad of other possible interventions (see here and see here and see here) that *might* offset the risks that follow a diagnosis of ADHD (see here).

Oh, and it appears that mindfulness and ADHD is a topic in the ascendancy [2]...

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[1] Poissant H. et al. Behavioral and Cognitive Impacts of Mindfulness-Based Interventions on Adults with Attention-Deficit Hyperactivity Disorder: A Systematic Review. Behav Neurol. 2019;2019:5682050.

[2] Xue J. et al. A meta-analytic investigation of the impact of mindfulness-based interventions on ADHD symptoms. Medicine (Baltimore). 2019 Jun;98(23):e15957.

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Wednesday, 26 September 2018

On transparency in science: lessons from the Pandemrix vaccine and 'partial' evidence-based practice

Minus any hype or sweeping generalisation, I want to draw your attention to a feature article recently published by Peter Doshi [1] titled: "Pandemrix vaccine: why was the public not told of early warning signs?" complete with some media interest (see here).

The feature is based around the vaccines developed to counter the 2009 flu pandemic that starred the H1N1 influenza virus which was sweeping across the globe at the time. The 2009 flu pandemic was potentially serious insofar as its infection pattern and fatalities linked to infection although in reality did not turn out to be quite the 'global killer' that was prophesied. The rush to bring to market a vaccine to protect lives and counter the rise of H1N1 also brought with it controversy from several perspectives [2]; some later talking points seemingly stemming from the inclusion of a specific adjuvant - AS03 - in some vaccine preparations, and data suggestive of a possible correlation between onset of narcolepsy and use of certain flu vaccines containing the AS03 adjuvant (see here). Narcolepsy - a sleep disorder - was one potential adverse side-effect talked about, but other labels/conditions were also the source of some inquiry too (see here). On the basis of the emerging published data, court cases ensued, some of which have apparently unearthed some "internal reports" suggesting that some manufacturers "were aware of other serious adverse events logged" in relation to certain H1N1 vaccines...

The Doshi feature goes through some of these 'revelations' that did not seem to have been made public at the time. He talks about an 'undisclosed problem' whereby one vaccine in particular, Pandemrix, seemed to have a greater frequency of various adverse events reported according to those internal company reports. Most worrying are the reports of 'fatal outcome' across different vaccine preparations, particularly Pandemrix. He also writes: "And the raw numbers of adverse events were not small" highlighting how in one of the latest internal reports dated March 2010 seen by himself (or at least, the British Medical Journal) over 5000 reports of "serious adverse events for Pandemrix" had been received by the company behind the vaccine.

It's timely that the Doshi feature appears now at the time of writing this post, just days after the Peter Gøtzsche - Cochrane drama (see here) and at the same time as other relevant pieces have been published (see here and see here [3]). The similarities around questions of transparency in science (particularly industry-derived science that has a public health aspect attached to it) are very noticeable. As is also the question of 'how much detail should the public be provided with?' when it comes to science in general and then specifically, science and science communication linked to the potential cost-benefit ratio of particular medicines or medical preparations. It's interesting too that Doshi also references some past debate in Germany [4] about the 2009 flu pandemic where it was apparently reported that "the German interior ministry rejected accusations that the ministry had ordered a less risky vaccine for top officials" in light of some newspaper headlines published at the time. 'All animals are equal, but some animals are more equal than others' perhaps springs to mind...

I don't think the issue of less than full transparency in science and the question 'how much detail should the public be provided with' are going to go away any time soon. Such issues strike to the heart of the matter of how peer-reviewed published science is seemingly only one part of a much bigger picture when it comes to the search for a complete truth. One wonders for example, how many other 'internal reports' lie in [research] file cabinets around the world that could conceivably influence evidence-based decisions on the effectiveness and safety of various medicines and other interventions indicated for various conditions? Without such documents ever seeing the cold light of day, how can science ever truly be said to be complete, transparent or indeed settled?

Such a 'transparency' situation also makes initiatives like OpenTrials - calling for all research to be more 'discover-able' and 'traceable' - all the more vital and important. Issues such as the requirement for pre-registration of all studies via databases such as ClinicalTrials.gov and importantly, the timely release and publication of results (see here) are pressing features. Study pre-registration (especially prospective registration) in particular, should perhaps be pushed a lot more than it currently is, and shouldn't just be reserved for big studies of drugs and medicines either.

Science is great and is getting better all the time. But it still has lots of issues and problems to overcome. A lack of research transparency seems to be a particularly important issue that, whilst starting to receive some much required attention, will if present, always mean that evidence-based practice really should be re-branded as 'partial evidence-based practice'. And that has lots of implications...

To close, given the subject matter included in the Doshi paper, I want to end with a reminder about not making sweeping generalisations. At the same time I'd also champion the words included in another recent article by Jørgensen and colleagues [5] (yes, also including Peter Gøtzsche as an author) responding to the idea that public confidence in public health initiatives such as vaccination may be "undermined" by even having such discussions in public. To quote: "Debates over sources of evidence must take place in public, especially when public health interventions are at stake." This is again, with the idea that science needs transparency - even better in the peer-reviewed domain - and closed door discussions rarely aid such transparency.

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[1] Doshi P. Pandemrix vaccine: why was the public not told of early warning signs? BMJ 2018;362:k3948

[2] Doshi P. Influenza: marketing vaccine by marketing disease. BMJ 2013;346:f3037.

[3] Jørgensen L. et al. Challenges of independent assessment of potential harms of HPV vaccines. BMJ 2018;362:k3694

[4] Stafford N. Only 12% of Germans say they will have H1N1 vaccine after row blows up over safety of adjuvants. BMJ 2009;339:b4335.

[5] Jørgensen L. et al. Response to Cochrane editors: Jørgensen, Gøtzsche and Jefferson. BMJ EBM Spotlight. 2018. Sept 23.

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Tuesday, 18 September 2018

On Cochrane and 'facts' and 'politics' in evidence-based medicine

The controversy surrounding the reported expulsion of Peter Gøtzsche from the Cochrane Collaboration (or should that just be Cochrane?) is something that I've been following for a few days now (see here). Cochrane, under the heading "Trusted evidence. Informed decisions. Better health", represents one of the premier go-to sources for evidence-based healthcare advice on a range of topics. Some of those topics have been previous fodder for this blog too (see here and see here for examples).

I don't profess to have any unique insight into the various goings-on leading to the reported expulsion of Gøtzsche and resignations of fellow members beyond that which has been discussed in various sections of the science media (see here and see here and see here). From what I gather, things look like they've been 'brewing' for a while with regards to Cochrane and the views and opinions expressed by some of those who are seemingly departing. Such a public spat however, is unlikely to be good for science or evidence-based medicine, and indeed may have some wider implications for some fundamentals of science and science communication...

One of the possible [late] precipitating events mentioned around the Gøtzsche saga was the publication of a quite scathing article by Lars Jørgensen and colleagues [1] (including Gøtzsche as an author) questioning the published results of a recent Cochrane review [2] titled: "Prophylactic vaccination against human papillomaviruses [HPV] to prevent cervical cancer and its precursors". The original review by Marc Arbyn et al garnered media headlines when published (see here) as per conclusions such as: "There is high‐certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26." A comforting finding by all accounts. Accompanying such efficacy data were other statements made by the authors on the basis of the evidence reviewed that: "The vaccines do not increase the risk of serious adverse events, miscarriage or pregnancy termination."

Jørgensen and colleagues however put forward their [peer-reviewed] view that the Arbyn paper fell short of the expected standards from Cochrane: "We do not find the Cochrane HPV vaccine review to be ‘Trusted evidence’, as it was influenced by reporting bias [3] and biased trial designs." They highlighted several 'issues' with the original review stretching from trial selection for the review, to the assessment of "serious and systemic adverse events" to potential "conflicts of interest." Similar sentiments had been voiced about other Cochrane reviews too that were subsequently pulled from the scientific literature. Feathers were inevitably ruffled (see here) by the Jørgensen paper, even as far as prompting a response from the journal that published the paper [4] about the peer-review process leading to publication of the critique. Things are getting serious when a journal has to defend its publication of a paper.

Without wishing to reduce this saga to any one event, I don't think it would be unreasonable to assume that the Jørgensen paper might have influenced matters quite considerably; perhaps even bringing them to a head. As per involvement on the Boesen paper [5] Gøtzsche is no stranger to calling out Cochrane reviews that seemingly don't make the grade, alongside also voicing opinions on various other matters down the years. To quote: "... in another book, [he] likened the pharmaceutical industry to "organized crime""; such forthright statements stretching back some years are unlikely to have made too many friends in certain circles.

As per the title of this post mentioning the words 'facts' and 'politics', one particular write-up of this saga I think hits the nail on the head. The opinion piece from Trish Greenhalgh [6] presents the two sides to this 'dispute': on the one hand is that the “crisis” is "philosophical (relating to the nature of facts)" and on the other, "political (relating to organisational governance)." The philosophical side of things is pretty evident as per the publication of the Jørgensen paper as a counter to the Arbyn paper. Greenhalgh mentions about how "Gøtzsche might be classified as an evidence-based medicine purist" given his views and sizeable contribution to various "statements on how to undertake and publish research." In this respect, his published views on the original Arbyn paper (and similarly in other reviews) seem to detail scientific standards not being met, or at least not being met to his and his co-authors standards. And certainly on points such as access to trial results and data, he's seemingly not alone in his concern (see here).

On the political side of things, well, at the time of writing we just don't know enough to reasonably comment. Greenhalgh mentions that: "The political explanation for Cochrane’s crisis relates to the tension between governing an organisation and respecting individual members’ academic freedom to express dissent." The fact that such dissent has over the years covered various important public health topics - "cast doubts about the safety of a vaccine against human papillomavirus (HPV), a cause of cervical cancer, and says psychiatry has “gone astray” by coercing patients into taking medication, such as antidepressants, they don’t want to use and that cause “brain damage” over the long run" - is likely to have really stretched those organisational relationships with Gøtzsche. Not least because immunisation and antidepressant use reflect important pillars of modern public healthcare and, historically, uptake of such medicines is very, very susceptible to differences in scientific views, opinions and beyond.

As to the idea mentioned by Greenhalgh that: "We should cut it [Cochrane] some slack while it gets its house in order", I'm not exactly sure how it's going to approach this 'house in order' requirement and what this means for the future credibility of Cochrane. Based solely on the 'facts' side of this saga, it strikes me that organisations like Cochrane actually need people like Peter Gøtzsche and their "evidence-based medicine purist" beliefs. They need them in order to critically (really critically) boil down the ever-growing research literature into scientifically sound statements for public and policy consumption without fear or favour. Minus such voices, it's more likely that evidence-based messages originating from such initiatives are perhaps going to be weakened, which in turn means that population healthcare is potentially going to suffer. Moreover, I assume also that just because Gøtzsche is reportedly not part of Cochrane any more does not mean that he won't be heard from again in the peer-reviewed domain...

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[1] Jørgensen L. et al. The Cochrane HPV vaccine review was incomplete and ignored important evidence of bias. BMJ Evidence-Based Medicine. 2018. July 27.

[2] Arbyn M. et al. Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors. Cochrane Database Syst Rev. 2018 May 9;5:CD009069.

[3] Jørgensen L. et al. Index of the human papillomavirus (HPV) vaccine industry clinical study programmes and non-industry funded studies: a necessary basis to address reporting bias in a systematic review. Syst Rev. 2018 Jan 18;7(1):8.

[4] Heneghan C. & Onakpoya I. Editors’ response to concerns over the publication of the Cochrane HPV vaccine review was incomplete and ignored important evidence of bias. BMJ Evidence-Based Medicine. 2018. Sept 12.

[5] Boesen K. et al. The Cochrane Collaboration withdraws a review on methylphenidate for adults with attention deficit hyperactivity disorder. Evid Based Med. 2017 Aug;22(4):143-147.

[6] Greenhalgh T. The Cochrane Collaboration—what crisis? BMJ. 2018. Sept 17.

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Tuesday, 22 March 2011

Autism and developmental history recall

The diagnosis of an autism spectrum condition is predominantly (nay exclusively) based on a subjective judgement of whether clinical behavioural criteria are met, also incorporating an analysis of a person's developmental history.

In other words, parents and caregivers are often vital to the diagnostic process as a function of their recall of their child's early medical and developmental onset history, and events leading towards the presentation of symptoms.

Early diagnosis of autism is the goal; although often, because of the way symptoms present or the finite resources available to access assessment services, there are delays from time of symptom onset / recognition to receipt of a formal diagnosis. In some cases, this delay registers in the years rather than months or weeks.

I say all this because a new paper by Cathy Lord and colleagues discusses an important issue relating to the recall of symptoms, the 'telescoping' effect in caregiver reports - that is, a bias based on the reporting of events. Telescoping can be forward or backwards; so remembering events either closer or more distant than they really are.

Before anyone takes this issue too personally, I must add that we all do it. Ask someone about when a recent event happened and the chances are that they will be slightly outside of the actual time frame - 'when did I last go out for a meal?', 'when did I last call my parents', 'at what age did my children start to walk' - all biased by our failing memory (assuming that there is no other corroborating evidence such as videos or diary entries).

Lord and colleagues suggested some significant telescoping effects when the Autism Diagnostic Interview (ADI) was administered to caregivers over various occasions of their child's early years (2,3,5,9 years of age), specifically in the area of language milestones (acquisition of language, use of phrase speech, etc). Importantly however, when it came to the age of first concern over symptoms, caregivers seemed to be pretty consistent.

What does this all mean?

Well when it comes to dating when symptoms started, current psychological theory would perhaps suggest that this date is an anchor point for parents / caregivers. Whether due to a realisation that symptoms present and the subsequent emotional effects of this (emotions and memory seem to be strongly connected) or the associated interactions with other people (teachers, health visitors, physicians) as a result, age of first concern seems to stick in the memory.

Dating the various features of language acquisition proved more difficult. I assume much of this is because many things related to language are not tied into just one date. Remember the scene in Meet the Fockers when the little boy utters his first words (I won't repeat them here!). Unless a child says such an extreme word, chances are most people won't be able to date accurately when their child's first word happened just from memory. Likewise can anyone name the date when their child went from using single words to phrase speech? With all the will in the world, most people will be inaccurate because again our memory needs some kind of anchor and such a transition process is often not tied into one date.

One final thing related to this paper: at the end of the abstract, the authors say: "Results support proposals to remove specific age-based criteria in the diagnosis of ASD". For those who read my post on the new proposals for the DSM-V entry for autism, and in particular the proposed changes to a 'dyad of impairments', this sounds to me like the DSM-V proposal is shortly going to become a reality.