 |
 |
Huw, I think this utilitarian perspective is more or less what has driven the current guidelines recommendations- with the threshold of 7.5% of CVD risk almost everyone older than 40 would be eligible to take statins. But, as this discussion indicates most people seem to be uncomfortable with the utilitarian ethics (not sure if the libertarian ethics is appropriate answer, either…) ben From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of Huw Llewelyn [hul2] Sent: Friday, November 02, 2018 9:50 AM To: [log in to unmask] Subject: Re: LDL and mortality (and use of statins) I’m sorry to arrive late to the discussion. Has anyone factored in the benefit to society as a whole of taking statins? I apologise if this had been aired already. This may be the primary source of the drive to advocate statins. It might be cheaper for society for large numbers to take a statin than to treat the numbers that could have been prevented from needing hospital and community care in due course. Society might thus benefit substantially but the probability of gain for the individual might be small. Perhaps we should take statins despite the small personal gain, inconvenience and the side effects for the common good. This takes us back to the old philosophical chestnut of balancing private gain versus the common good. Others may gain privately too eg those who sell statins. Others may experience inconvenience eg those who have to prescribe and monitor the treatment. Huw On 2 Nov 2018, at 15:49, McCormack, James <[log in to unmask]<mailto:[log in to unmask]>> wrote: Thanks Ben for your insight as well. It has been fun. I very much agree with the statement in your great JECP article "Thus, the use of statins is a quintessential preference‐based decision” - pretty much says it all - clinicians just need to have the tools and the skills to do this - like anything else in life it requires the passion to do healthcare this way and then practice, practice, practice. James On Nov 2, 2018, at 8:31 AM, Djulbegovic, Benjamin <[log in to unmask]<mailto:[log in to unmask]>> wrote: This has been one of the most fascinating discussion we have had in this discussion forum over the years, and I want to thank James for starting it and all others for phenomenal insights. It contains all ingredients that makes practice of medicine so complex ( and truly fascinating)- from uncertainties in prediction to social construction of practice of medicine to who should decide and high decisions should be made. I just want to add a couple more comments to the post that transpired in the last 24 h: 1) Michael Powers correctly pointed out that even when it comes to individualization of treatment, our “best bet is the AVERAGE of the net expected benefits, harms, and costs” I have already cited our recent paper making this argument : https://www.ncbi.nlm.nih.gov/pubmed/30251305) and here is a modeling exercise for individualizing treatment of statins for primary prevention https://www.ncbi.nlm.nih.gov/pubmed/26555150 2) however, Owen and others cogently argue that models are context-free and hence they may not be superior to (a knowledgeable) practitioner when it comes to individualizing care. Owen also argues or implies ( at least the way I understand his posting) that a practitioner should only focus on the problems that the patient vocalizes and not address any other issues in an asymptomatic patient. [ this may also be optimal or pragmatic way to practice given myriads of decisions that a practitioner has to make; on average we make about 200 key health decisions every day, and we collect about 1,000 data points per patient encounter), the practitioner cannot possible engage in discussion of every single issue that can be addressed , or even normatively recommended ] But, in doing so, the practitioner ignores patient’s V&P or at least selectively attend to them ( if the issue of, say, cardiovascular risk is not mentioned at all, then, by definition, the patient’s views are ignored] 3) James argues that the only ethical way to proceed is to consult patient’s V&P ( even if we don’t know that engaging patients based on the existing information such as CVD risk models would ultimately be more helpful than harmful as the impact analyses have not be done) Which brings us to the most interesting question of all: are patients’ V&P absolute ? Currently, at least in the US, this seems to be the case ( in adult, cognitively competent patients). [ I provided examples of two patients who chose to die by refusing intervention that would have almost certainly save their lives- this was RBC transfusion in patient who died due to GI bleeding as they could not accept red blood transfusion on religious ground]. But, what about V&P of all those interventions that physicians never mention at the first place ( as per #2 above)? Is there a problem with this “ethics of silence”? Sorry for a long post- thanks all for a fascinating discussion ( and sorry if I misinterpreted some of the views of the folks I mentioned) Ben On Nov 2, 2018, at 4:42 AM, Owen Dempsey <[log in to unmask]<mailto:[log in to unmask]>> wrote: To respond to James questions: 'what would I do if I found a raised BP ...?" and what of SDM: 1. As far as what would I do if I was given a raised BP to manage: once the BP is found to be high, the die is cast, the BP now signifies the clincian to read the guidelines and offer to do what they say. 2. However with regards to shared decision making: I would find it hard to implement an intervention (taking a BP opportunistically) that I thought would be more likely to do harm (reduce the persons potential to function well) than good even if the lay person consulting me wanted me to do that. The problems with eliciting values in SDM are: a) there is always an imbalance of power in the consultation (Joseph-Williams et al, 2014)because of : (i)the doctors status and assumed knowledge of what is ‘good practice’, and (ii) because institutions and social relations produce normative (effective) truths, through guidelines for example, that induce both the care provider and the lay citizen to over-value preventive interventions. For example women over value the benefits of breast cancer screening (Biller-Andorno, 2014). I have found it helpful to think that our values are, (and we need them to be), within limits, constructed for us as the way we form our sense of our selves (identities) and sense of purpose in life. This insight shows us why some individuals tend to over invest emotionally in some of EBM’s illusions about preventive care. And, it reveals a duty of care that care providers have not to exploit that over investment. Biller-Andorno, N.J.P. (2014) Abolishing Mammography Screening Programs? A View from the Swiss Medical Board. N Engl J Med, 370: 1965 -1967. Joseph-Williams, N., Edwards, A., & Elwyn, G. (2014) Power imbalance prevents shared decision making. BMJ, 348. On Fri, Nov 2, 2018 at 6:06 AM Michael Power <[log in to unmask]<mailto:[log in to unmask]>> wrote: I have been following this discussion with some interest, but the issue of explaining uncertainties (and biases) has been missed. (A 5-year prediction for an unwanted outcome is less scary than a 10-year prediction. I won’t discuss the potential for biasing decisions any further.) Statisticians know the difference between a prediction interval and a confidence interval, but seldom give us both. And, I have never seen a risk calculator that gives either - although, of course, you can use risk calculators to explore the effects of uncertainties/variations in the inputs. https://datascienceplus.com/prediction-interval-the-wider-sister-of-confidence-interval/ Folk wisdom knows how to use prediction intervals to inform decision-making: plan for the worst, but hope for the best. To this we should add: act on the best bet. The best bet is the average of the net expected benefits, harms, and costs. I haven’t seen many decision aids that help people identify and weigh up the chances of good and bad outcomes x their values. Is this the sort of work that should be on our To Do lists? Michael Sent from my iPad On 2 Nov 2018, at 04:22, McCormack, James <[log in to unmask]<mailto:[log in to unmask]>> wrote: Totally agree - definitely more work to do but at least I think we are singing from the same song sheet At the risk of going down another rabbit hole, what do others think. James On Nov 1, 2018, at 8:14 PM, Neal Maskrey <[log in to unmask]<mailto:[log in to unmask]>> wrote: Perfect for me James. Great stuff. Presumably the point you’d make is its difficult to determine the best thing for an individual from population level data then. We have to know the population level data and then use that to have the best conversations we can with individuals, which is of course the best known and most often used definition of EBM! My point would be we still have to work to do on those conversations, sometimes. Neal Neal Maskrey On 1 Nov 2018, at 22:15, McCormack, James <[log in to unmask]<mailto:[log in to unmask]>> wrote: Thanks Ben - I think you have illustrated my point well - which I appreciate. The debate is way more ethical than scientific in my mind. I totally agree that scenarios that present the two outcomes as certain death versus certain living are the most difficult ones to wrap ones SDM head around. Most of us would think that anyone who would choose not to take such a treatment should have their head examined - however we all know or have read about examples were people make these decisions and I believe most countries (I think) allow this except for children. in the paper I mentioned earlier, that I wrote with Glyn Elwyn, entitled "Shared decision is the only outcome that matters when it comes to evaluating evidence-based practice” we address this issue as well. Maybe a more nuanced scenario is this A patient is dying of cancer - there is a chemo treatment that has definitely been shown on average to make people live 2 months longer - as you know at present in medicine, in almost all these sorts of cases, we try our best to discuss risk estimates (how long will they live) and the benefits and harms with all people and help them make a decision as to whether or not they wish to take treatment. Let’s assume 50% of people opted to not take this proven treatment after doing SDM. Someone says, hey you can’t do risk assessment and SDM until you have done a proper impact analysis If we did an impact analysis on this scenario the outcome of the group that got SDM (remember 50% would refuse treatment) would be that mortality would be increased compared to what would happen if we gave the treatment to everyone. Because of this impact analysis should we say that risk discussions in this scenario should be prohibited because mortality was increased. Personally, I think it is imperative to discuss the benefits and the harms with these patients and help them make a decision even if the decision on average will shorten their life What do you think? Is my scenario legitimate? James On Nov 1, 2018, at 6:25 PM, Djulbegovic, Benjamin <[log in to unmask]<mailto:[log in to unmask]>> wrote: James, Impact analyses of risk prediction models are really not that controversial- I attached one of the BMJ tutorials that nicely explained why we need impact analysis. But, you are raising an interesting and important ethical question- are patients’ values and preferences (V&P) absolute? What is physicians’ role? Only to inform, or to steer patients’ toward more beneficial decision (defined as achieving better health outcomes)? Let me give you two real-life examples: • Two female patients -55 and 63 age- previously in good health, presented at two different occasions with a similar life-threatening condition. If you do not intervene, they will most certainly die. You have a treatment at your disposal that is close to 100% effective. They are absolutely well informed about pro and con of Rx. • Will you abide by the patients’ V&P even if they refuse treatment? The situation is somewhat different than the one we are discussing-where you argue that informing patients is goal per se - even though we do not actually know if that information will lead to better health outcomes. I decided to further illustrate the point which I think you are making- as long as a patient is informed (to best of our knowledge)- such a decision is OK. Or, is it? ben From: McCormack, James [mailto:[log in to unmask]] Sent: Thursday, November 01, 2018 5:54 PM To: Djulbegovic, Benjamin <[log in to unmask]<mailto:[log in to unmask]>> Cc: [log in to unmask]<mailto:[log in to unmask]> Subject: Re: LDL and mortality (and use of statins) Thanks Ben - I think a number of us are talking in circles because a number of us (maybe me as well) are talking in general and not specifics - to clarify, maybe this would help 1) Can one of the people in this discussion, who would like to see an impact analysis about this, describe specifically what impacts (outcomes) you would be looking at? 2) Ben, how would you define "more good than harm”? Let me give a few specific scenarios from a hypothetical impact analysis and I will tell you what I think about them The intervention is CVD risk discussions and then shared decision making - realizing that some people will decide to treat and others won't SCENARIO A - impact analysis shows fewer overall deaths and CVD - GREAT (because of this benefit and because SDM occurred) SCENARIO B - impact analysis shows no difference in overall deaths and CVD - UNFORTUNATE (but at least SDM occurred) SCENARIO B - impact analysis shows increased mortality and or CVD - REALLY UNFORTUNATE (but SDM occurred and individuals are allowed to make a decision not to treat - if one chooses not to take a treatment that is effective, then more CVD will occur) Remember, with SDM, inconvenience, costs, side effects, false negatives, false positives, etc don’t come into any impact analysis because if they were properly informed (I know that is not easy and may be only idealistic) the individuals would have already taken these points into account in the decision. My point is, an impact analysis would be REALLY scientifically interesting but regardless of the outcome we should still do SDM around CVD risk assessment and treatment. Finally, can anyone describe an outcome of an impact analysis of SDM in this context that would lead to us agreeing that SDM was a bad idea? If at all possible could responses please for now just answer these specific questions as specifically as possible - then of course say anything else you would like. Just trying to prevent circular arguments. Thanks and it is great that people are interested in this issue. James On Nov 1, 2018, at 4:30 PM, Djulbegovic, Benjamin <[log in to unmask]<mailto:[log in to unmask]>> wrote: James, I understand desire to empower “right-based” autonomous approach to decision-making, but without impact analysis, we can never fully understand if information we “shared” with patients will do more good than harm. [This is even if we knew how to present available evidence, which we don’t. It has been said that “communication is considered effective when it leads to engagement in recommended behavior, when the target audience pays attention to the message, when it results in improved acquisition in knowledge, acceptable effects on emotions, and accurate judgments of perceived risks and benefits, and when it results in a message that is credible, accurate, useful, relevant, comprehensive, trustful, clear, and easy to understand.” This remains as aspirational as ever.] I agree with Juan, Mohammed and others- we do need impact analyses, but they are rarely done. In the meantime, however, we should use your calculator (with all caveats discussed here) ben From: Evidence based health (EBH) [mailto:[log in to unmask]] On Behalf Of McCormack, James Sent: Thursday, November 01, 2018 4:16 PM To: [log in to unmask]<mailto:[log in to unmask]> Subject: Re: LDL and mortality (and use of statins) Hi Mohammed - thanks for interjecting. Happy to try to answer but you need to define effectiveness. My definition of effectiveness, when it comes to risk prediction and risk reduction - is that a shared decision was made - because these conditions are asymptomatic and we will never be able to figure to if someone actually benefitted - even if they did. For many other medical conditions my definition of effectiveness would be very different. James On Nov 1, 2018, at 4:05 PM, Mohammed T. Ansari <[log in to unmask]<mailto:[log in to unmask]>> wrote: If I could interject James. If effectiveness in risk prediction is not important to be established, then are we not merely manufacturing a narrative for the patient to use in their decision-making? Why would it matter to even bring it into shared decision-making, I am not sure. Just a silly thought running through my head right now. m On Thu, Nov 1, 2018 at 6:59 PM McCormack, James <[log in to unmask]<mailto:[log in to unmask]>> wrote: Juan - IMHO you are completely missing my point by not addressing my comment about “Why do we even need an impact assessment" It has nothing to do with "Absence of evidence is not the same as evidence of absence”. Maybe this will help. Let’s assume there is a really good study that shows definitively that doing CVD risk assessments WORSENS outcomes and by that I mean more people have CVD events if they have risk explained to them. Even that wouldn’t stop me from doing CVD risk assessments and doing the best I can to explain benefits and harms to the patients because I am 100% OK if people don’t take proven treatments to reduce CVD risk. They are allowed to make that decision. The only true impact assessment that could be of value for CBD risk assessment would be to assess if the patient truly understands what we are trying to explain to them about CVD risk. But I don’t think that is the type of validation you are talking about. James On Nov 1, 2018, at 2:47 PM, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -this quote, Rod, is very popular in EBM (‘Absence of evidence is not the same as evidence of absence") but we cannot use it to justify sending patients to Lourdes (Sanctuary of Our Lady of Lourdes, France) -we need to add evidence to something so popular as table of risk, in general, and CV table of risk in this debate -the development of a clinical prognostic prediction rule is just a first step which should be followed by its validation and impact assessment -un saludo juan gérvas @JuanGrvas El jue., 1 nov. 2018 a las 22:36, McCormack, James (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: Hi Owen - seems like people are having fun with this discussion which is great. I very much appreciate and agree with many of your concerns about the problems of screening and unnecessary tests. However I really would love to hear your opinion (as I asked in the previous email) about what one should do once a blood pressure has been measured. I suggested the approach below - do you have any issues with this or would you do something differently? One additional comment - you make the statements that “I might judge it worth the risk to the patient” and “the onus is on the carer to justify taking the BP”. IMHO both of these approaches are antithetical to doing shared-decision making because the only way to address these issues is to have asked the patient about their values and preferences once having explained the potential risks, benefits and harms. It is not up to the clinician to decide if a blood pressure should be measured - that should also be a shared-decision - it is not for us as health care providers to be the judge. Hope the question and comments makes sense. Here is what I thing is the best thing to do 1) Remember that a single blood pressure reading is equivalent to reading one page of War and Peace and saying “I get the story” 2) Do multiple measurements over the next few weeks - ambulatory or office or whatever 3) Once we think we have a reasonable estimate of what we think is their blood pressure, use this number and all the other patient information with a cvd risk calculator and get a ballpark estimate of CVD risk and explain roughly what risk factors mean in their context - also explain that these risk calculators typically overestimate risk so this is the worst case scenario 4) Explain why the specific thresholds in guidelines are extremely arbitrary 5) Encourage the person to be physical active and healthy (whatever that is) eating 6) Discuss risks benefits and harms of treatment based on the best available evidence and then help the person make a shared-decision - and then support it. What do you think of that approach? I realize this would take time but there is no hurry - this could be done over multiple visits over weeks to months. On Nov 1, 2018, at 2:10 PM, Owen Dempsey <[log in to unmask]<mailto:[log in to unmask]>> wrote: Thanks Ben for the note on context and the unknowable risk at individual level, I'll expand briefly on the points raised about the particular case taking a BP opportunistically in a consultation. The consultation context would entirely determine when I would take a BP on an asymptomatic patient. For example: I might be asked by a very anxious patient to take a BP and think that it would undermine a therapeutic relationship with that patient not to, so then I might judge it worth the risk to the patient of taking the BP. The humble BP is a perfect tool for teaching student about over investigation; students might be thinking: its low tech, quick, what harm could it possibly do, and after all isn't hypertension a killer? etc. First point, as we all know, apart from hospital doctors, is that in primary care the prevalence of disease is a lot lower than in hospital - this is an important point, the second is that for an asymptomatic population clinical judgment should prioritise a duty of care that is not at the expense of the patient, that is to say should only actively offer intervention, like taking a BP, if confident the care will do more good than harm for that individual. In other word the onus is on the carer to justify taking the BP. Thirdly, the humble BP is a potent intervention: James has outlined the potential cascade of further investigations, and possibly treatments, all of which can lead to harm, not least because of false positive results. Fourthly, the humble BP, today, has the status of a powerful care-totem: it is symbolic of both caring and being cared for. EBM institutions have in part been responsible for raising expectations of preventive medicine and risk measurements, and it is now believed by many that 'knowing risk (and your BP) is a good thing.' Lay people often expect a BP to be taken, and care providers may feel safer and more comfortable and caring if they satisfy that expectation and comply with a professional norm at the same time. But, taking the BP may be inflicting a form of symbolic violence and exposing the patient to risk, rather than just estimating their risk. We are a long way from the point where it is culturally the norm to be wary of risk assessments - and there is no need to be dogmatic about every individual case, expectations need to be managed, but this is, I think, the direction we should be heading in. Continuing to take BPs opportunistically: takes time, distracts from the patient's complaint and suffering, raises anxiety and further expectations, can lead to costly further investigation, over diagnosis and over treatment, diverts resources from other forms of care, and it depersonalises making it harder to respond caringly to patients suffering as individuals Owen On Thu, Nov 1, 2018 at 5:31 PM Djulbegovic, Benjamin <[log in to unmask]<mailto:[log in to unmask]>> wrote: Rod, Not to presume to answer for Owen, but the main feature of clinical judgement is that is contextual, while risk models are not. Also, what is missing in this interesting discussion is acknowledgments that risk is a group phenomenon, and is knowable and can be quite accurately assessed as a population-based measure. However, risk in any individual patient is ultimatelyunknowable. It is this latter where clinical judgment applies. (in somewhat related article, John Ioannidis and I just published an article addressing some of the issues related to risk understanding; I think it is made as an open access: https://www.ncbi.nlm.nih.gov/pubmed/30251305) Best ben From: Evidence based health (EBH) [mailto:[log in to unmask]<mailto:[log in to unmask]>] On Behalf Of Rod Jackson Sent: Thursday, November 01, 2018 10:00 AM To: [log in to unmask]<mailto:[log in to unmask]> Subject: Re: LDL and mortality (and use of statins) ________________________________ [Attention: This email came from an external source. Do not open attachments or click on links from unknown senders or unexpected emails.] ________________________________ Dear Owen. I have always been intrigued by the advice to ‘use clinical judgement’ which you use in response to James’s question about when to measure blood pressure. Having trained in medicine and also taught many medical students, doctors and other health professionals, I see my role in trying to inform that clinical judgement. So would you mind expanding on your answer to James’s question, assuming it had been asked by a final year medical student who is spending a training period based in a general practice. Cheers Rod On 2/11/2018, at 12:29 AM, Owen Dempsey <[log in to unmask]<mailto:[log in to unmask]>> wrote: Again a second addendum, becauseI think its important: I have been asked: "If I am interpreting you correctly, what you are saying is, you think that blood pressures should never be measured unless a person is symptomatic. I’m not saying that is wrong but is that what you are saying?" The key phrase here is 'unless a person is symptomatic' which begs the questions: what symptoms and who decides. I would argue that the systems of screening and risk assessment that cause harm are those that send postal invitations out, or make phone calls, to populations of asymptomatic individuals in the community (that is to people who are not actively complaining or seeking intervention of any kind) ,and especially if, for example, saying things like "and your GP thinks this is a good idea" which is written on invitations for breast cancer screening where I live in Scotland). However, if a person visits a health carer for any symptomatic reason then I would leave whether to take a blood pressure up to that health carer, whilst encouraging that carer to be aware of the dangers of over investigation, and false positives in populations where a disease/risk factor is of low prevalence. The question of when to check the BP in a face to face 1:1 consultation in surgeries is a matter for individual clinical judgement. We can all think of scenarios where we would and would not check the BP, but I would avoid checking a BP unless it seems clinically relevant to me. Owen On Wed, Oct 31, 2018 at 2:18 PM Owen Dempsey <[log in to unmask]<mailto:[log in to unmask]>> wrote: Following a reply I would like to share an addendum: If I was asked for example: "I would imagine you would agree that treating blood pressures of 200/120 likely provides a reasonable overall benefit - if so how does one pick this up without sometimes measuring blood pressure?" The key phrase here is 'reasonable overall benefit' .. benefit to the individual perhaps, although I would prefer to say a reasonable 'chance' of benefit; but collectively I would say that population based screening of the asymptomatic population in order to detect occasional very high blood pressures causes more harm than good. If the population isn't screened then the person with the asymptomatic very high BP would go undetected, and may come to harm because of it. However this does not, in my view, justify population based screening because: 1. the minimum level at which BP would benefit from treatment is not known, this leads to many false positives and much over diagnosis, and morbidity, 2. treating the borderline cases leads to expense and side effects, 3. there are opportunity costs in terms of what the resources used to screen could be spent on, screening for example takes away time and money to be spent on people who are ill, 4. there are financial implications for individuals and for health services, 5. and this kind of population based care makes it harder for individual practitioners to provide inter-personal care because people are de-individualised by the process. The health services, and individuals, have limited resources, this means that the care that can be provided is not without limits. I do think it is reasonable for the population at large to made aware of healthy lifestyle advice, such as smoking is bad for everyones health, just as poverty, and lack of access to healthcare is bad for everyone's health. Owen On Wed, Oct 31, 2018 at 11:16 AM Owen Dempsey <[log in to unmask]<mailto:[log in to unmask]>> wrote: Dear all, I think there are two very important concepts being discussed in this thread: First, just to say, I support Juan's assertion that prediction and decision rules are intertwined, so offering risk assessment is never innocent of harm, and secondly, I consider the basis on which evidence can possibly guide asymptomatic risk and screening assessment practices: I suggest that should never rely on the impressions formed solely on the effect on the intended target. Two issues to comment on: 1) cardiovascular risk assessment for asymptomatic populations: Offering risk assessments to asymptomatic populations (including, for example,screening for heart disease risks or cancer) is never simply a case of enabling informed decisions to be made. Even offering such a risk assessment creates anxiety and a fear for future health. Providing such a risk assessment enforces a decision: whether or not to take action on the basis of the result. In addition, the process provides a false sense that knowing one's risk will improve life in the long run. Offering risk assessments, (and screening tests), to asymptomatic populations actually takes away the freedom of the individual to lead his or her life free of the anxiety induced by the offer, and its associated sequelae. A risk estimate or a screening test result, is what could be called a signifier, that his to say: it signifies the 'patient; and the 'carer', to take the right action, to make the right decision 'for them'. There is choice but it is a 'set up', a constrained choice when the freedom not to know has already been lost. Risk assessment and treatment decision cannot be divorced from one another, and so risk assessment always carries risk of harm. This matters because if the anticipatory diagnostic process is likely to cause more harm than do good, either individually or collectively , or both, then it should not be offered, and there should be no population based programme for it. I have argued before, and in my book 'Anticipation and Medicine", that such programmes (in the wealthier nations) will inevitably cause more harm than good and should not be offered 2) Do Statins for primary prevention reduce overall mortality? If they don't then this is a logically empirical reason why they should not be offered. And, even if they do, this is insufficient reason, on its own, to warrant a population based practice. This is because it is always insufficient to ask "Does it work?", meaning "Does it reduce heart disease deaths, or overall mortality?". There are other important questions: Other questions that should address are, For example: 1. Do authoritative institutions take into account, as harms, inevitable harms, unpredictable adverse events, and overdiagnosis when warranting guidelines (and how do we know)? 2. Do they take into account the opportunity costs of such programmes (for example, the reduced amount of money available to spend on other services?) 3. Do they take into account the way the market induces carers and the lay public to over estimate the actual benefit of such care? This matters because, as with much of such care in the wealthier nations, such products (as cardiovascular risk assessments, cancer screening, and Statins) cause harms: 1. direct and visible, as in side effects, 2. and invisible: as in over diagnosis, 3. and financially to individuals, 4. financially to public health services for the poorest especially, and 5. unknown ( even unknowable) harm for life to fulfil its health potential This is why risk assessment can be harmful, and why we should care whether or not patients take Statins. Note that this topic is the subject matter of the short book I have had published recently and which I would recommend for students/carers being taught about real EBM. Best wishes Owen On Wed, Oct 31, 2018 at 9:56 AM Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -to finish this debate 1/ using any cardiovascular risk calculator in the consultation room to take decisions is like using a magic crystal ball to take decisions (no scientific base, but could be shared decisions) 2/ of course i never even think that you "cherry pick the meta-analysis", sorry, i never ever think that; i wrote " if your prefer cherry picking by the authors of meta-analysis" what is a critic to the way meta-analysis are done, by cherry picking and 3/ i’m not pro or con statins, i'am only trying to debate about its rational use -thanks in any case for your intelligent ideas and sorry for my horrible English -un saludo juan gérvas @JuanGrvas El mié., 31 oct. 2018 a las 4:17, McCormack, James (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: Thanks Juan for your response. 1) really glad you liked the calculator - and thanks to other people who said they also found it useful 2) risk calculators are all about how to help clinicians and patients make decisions - but agree they are not appropriate to use to decide on a specific threshold for treatment 3) not sure why a risk calculator that is used to give ballpark estimates of CVD needs to undergo a formal impact analysis - a formal impact analysis is used to evaluate if a prediction rule will be beneficial or harmful. When used for education to help make ballpark estimates the only outcome of interest is whether or not the person was properly informed - whether CVD events are impacted is irrelevant - a shared decision is the important endpoint 4) I didn’t cherry pick the meta-analysis - if you look at the actual numbers all MAs on this topic show pretty similar results - one should never just read the conclusion of a meta-analysis because as we have shown, many people who publish MAs don’t know how to interpret confidence intervals https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-13-134 The MA I sent and the one you suggested show pretty much the same thing - which is to be expected as they looked at mainly the same trials - although one (JACC) included a few more trials See below for the result of each MA - the one I used was the JACC and your's was the AIM MA. The overall CVD and mortality point estimates were almost identical, one showed a larger point estimate for stroke and the opposite for MI - but there is such an overlap with the confidence intervals you can’t really say they are any different. Importantly, every point estimate leans in favour of statins. Just for the record I’m not pro or con statins - I really don’t care if people use them or not - just that people are given the opportunity to make decisions based on the best available evidence. A) Any cardiovascular event JACC MA - 0.81 (0.75-0.89) – primary outcome endpoint so not any CVD event but similar Arch Int Med MA - 0.81 (0.74-0.89) B) Mortality JACC MA - 0.90 (0.82-0.99) Arch Int Med MA - 0.92 (0.76-1.13) C) Stroke JACC MA – 0.74 (0.55-0.99) Arch Int Med MA - 0.92 (0.76-1.10) D) MI JACC MA - 0.78 (0.67-0.94) - CHD Arch Int Med MA - 0.69 (0.52-0.91) Hope all the above makes sense James On Oct 30, 2018, at 1:59 PM, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -excellent tool your risk calculator cvdcalculator.com<http://cvdcalculator.com/> -but it is just a risk calculator, a table of risk not a table of decision -to my knowledge you have not undergone formal impact analysisso you cannot use in a clinical context -you cannot transform predicition rules in decision rules https://www.ncbi.nlm.nih.gov/pubmed/16461965 -about women and statins i prefer cherry picking by myself but if your prefer cherry picking by the authors of meta-analysis: "Statin therapy is an effective intervention in the secondary prevention of cardiovascular events in both sexes, but there is no benefit on stroke and all-cause mortality in women" .https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1195535 -un saludo juan gérvas @JuanGrvas El mar., 30 oct. 2018 a las 20:57, McCormack, James (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: Thanks Juan - just a few comments - thanks for the info about the sugar industry - very interesting A) CVD risk assessment 1) not sure why using CVD risk assessments needs to reduce CVD morbidity or mortality - in my opinion their only purpose should be to inform patients about a ballpark estimate of their CVD risk 2) agree that guidelines use them to inappropriately to establish treatment thresholds 3) what do you think of the risk calculator we developed cvdcalculator.com<http://cvdcalculator.com/> - always looking to make it better so would love feedback on how to improve it or if we got something wrong we would be happy to fix it B) Women and statins I think cherry picking 2 studies that didn’t show a statistical benefit is not the way one should discuss evidence. The meta-analysis (link below) seems to suggest that when you look at all the evidence there is a benefit in women - or am I missing something - would love to hear why this MA is flawed or what the concern is - you said you had lots of concerns https://www.ncbi.nlm.nih.gov/pubmed/22300691 James On Oct 30, 2018, at 12:25 PM, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -sorry for the delate in answering, James, i thought the question was over -about my two questions 1/ do you agree with "it is uslees the global cardiovascular risk assessment in the primary prevention of cardiovascular disease in adults”? There is currently no evidence reported that the prospective use of global cardiovascular risk assessment translates to reductions in CVD morbidity or mortality. THIS A KEY POINT IN PRIMARY PREVENTION AS IT IS USELESS THE USE OF ANY PREDICITION RULE https://bmjopen.bmj.com/content/7/3/e013650?rss=1 Prediction rules are not decision rules but may clinical guidelines transform predicition rules in decision ruleshttps://www.ncbi.nlm.nih.gov/pubmed/16461965 2/ do you agree with "sugar lobby paid scientists to blur sugar's role in heart disease”? "Sugar Industry and Coronary Heart Disease Research. A Historical Analysis of Internal Industry Documents" Together with other recent analyses of sugar industry documents, our findings suggest the industry sponsored a research program in the 1960s and 1970s that successfully cast doubt about the hazards of sucrose while promoting fat as the dietary culprit in CHD.https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2548255 -about your questions only one merit more debate, in my opinion 1) reduce cardiovascular events in secondary prevention? - I think they do Yes, almost no doubt in males. Lot of concern in females For example: Scandinavian Simvastatin Survival Study (4S). Both CHD and total mortality were significantly reduced in men; however, there was no significant reduction in CHD mortality and no benefit on total mortality in women (RR, 1.16; 95% CI, 0.68-1.99) Cholesterol and Recurrent Events (CARE). CHD mortality was significantly reduced in men but not in women -un saludo juan gérvas @JuanGrvas El mar., 23 oct. 2018 a las 22:34, McCormack, James (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: Thanks Juan for agreeing to participate and appreciate your responses - see below for my response - capitals not because I am yelling but so you can easily see my response On Oct 23, 2018, at 12:32 PM, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -thanks, James, everything is clear -my answers in bold by your questions -but two questions for you: 1/ do you agree with "it is uslees the global cardiovascular risk assessment in the primary prevention of cardiovascular disease in adults”? NOT SURE WHAT YOU MEAN - DO YOU MEAN THAT RISK ASSESSMENTS (FRAMINGHAM ETC) ARE OF NO VALUE OR THAT LOWERING RISK BY STOPPING SMOKING, DECREASING BLOOD PRESSURE, BEING PHYSICALLY ACTIVE OR EATING HEALTHY FOOD IS USELESS 2/ do you agree with "sugar lobby paid scientists to blur sugar's role in heart disease”? I HAVE NOT SEEN EVIDENCE THAT THEY HAVE BUT I SUPPOSE IT IS POSSIBLE. CAN’T INFER MOTIVE HOWEVER. PERSONALLY I THINK WE ARE DEMONIZING SUGAR IN A SIMILAR WAY IN WHICH WE DEMONIZED FAT 40 YEARS AGO. THE PROBLEM IS THAT TO ANSWER NUTRITION QUESTIONS LIKE LOW FAT VS LOW CARB REQUIRE HUGE TRIALS OVER YEARS AND I DON’T BELIEVE THESE WILL EVER BE DONE. I HOPE I AM WRONG Statins based on the best available evidence - given that as with all evidence, it is never perfect - 1) reduce cardiovascular events in secondary prevention? - I think they do Yes, almost no doubt in males. Lot of concern in females INTERESTING - I THINK EVERY META-ANALYSIS I HAVE SEEN SHOWS THAT THE RELATIVE BENEFIT IS SIMLAR IN MALES AND FEMALES - WHAT IS YOUR TAKE ON THIS OR YOUR CONCERN 2) reduce mortality in secondary prevention? - I think they do Yes, almost no doubt in males. Lot of concern in females 3) reduce overall SAE in secondary prevention? - I think they do Yes, almost no doubt in males. Lot of concern in females 4) reduce CVD events in primary prevention? - I think they do No. And we know it from more than two decades I THINK EVERY META-ANALYSIS I HAVE SEEN SHOWS THERE IS A RELATIVE BENEFIT WHEN IT COMES TO CVD IN PRIMARY PREVENTION - WHAT SYSTEMATIC REVIEW OR MA DO YOU HAVE SHOWING NO BENEFIT - REMEMBER THE REASON WE THINK IT WORKS IN SECONDARY PREVENTION IS BECAUSE OF SYSTEMATIC REVIEWS AND MA FROM A COMBINATION OF INDUSTRY AND NON-INDUSTRY TRIALS 5) reduce mortality primary prevention? I think likely - all the point estimates are in favour but meta-analyses differ in whether or not the p-value is <0.05 https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-13-134 - they very likely don’t increase mortality No. And in any case, if yes, very little effect so harms are more important than benefits AGREE 6) reduce SAE in primary prevention? they seem not to but I also believe that there is much inconsistency in definition/reporting of serious adverse events that while interesting we must remember that this is a secondary analysis and is really only hypotheses generating No. With regards to tolerability 1) RCTs in general don’t show that the adverse effects are higher in the statin group compared to placebo - however the collection and reporting of adverse effects in all trials is at best weak Don't forget cerivastatin. RCT usually are not powered for adverse effects DISAGREE - IF YOU THINK THAT ADVERSE EFFECTS (ABOVE PLACEBO) ARE SO PREVALENT, THESE STUDIES EVEN INDIVIDUALLY ARE MORE THAN POWERED TO PICK UP ADVERSE EFFECTS LIKE MUSCLE ACHES ETC - YO ARE CORRECT IN THAT THEY WON’T PICK UP ADVERSE EFFECTS THAT ARE SAY 1/1,000 2) enough people complain of muscle aches while on statins that it likely is a real issue but it is really hard to put a number to the incidence We can measure adverse effects with a proxy: rate of adherence to statin therapy was only 50% at six months, and further declined at one year. DISAGREE - ADHERENCE IS A TERRIBLE PROXY MEASURE OF ADVERSE EFFECTS - SOME OF THE ADHERENCE MAY BE DUE TO PERCEIVED INTOLERABILITY BUT THE VAST MAJORITY IS THAT PEOPLE DON’T PERCEIVE A BENEFIT, DON’T LIKE TAKING PILLS, DON’T LIKE THE INCONVENIENCE OR THE COST -un saludo juan gérvas @JuanGrvas El mar., 23 oct. 2018 a las 0:14, McCormack, James (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: Hi Juan - agree this is an old debate but in debate it is always good to find common ground. Would you agree/or disagree with the following Statins based on the best available evidence - given that as with all evidence, it is never perfect - 1) reduce cardiovascular events in secondary prevention? - I think they do 2) reduce mortality in secondary prevention? - I think they do 3) reduce overall SAE in secondary prevention? - I think they do 4) reduce CVD events in primary prevention? - I think they do 5) reduce mortality primary prevention? I think likely - all the point estimates are in favour but meta-analyses differ in whether or not the p-value is <0.05https://bmcmedresmethodol.biomedcentral.com/articles/10.1186/1471-2288-13-134 - they very likely don’t increase mortality 6) reduce SAE in primary prevention? they seem not to but I also believe that there is much inconsistency in definition/reporting of serious adverse events that while interesting we must remember that this is a secondary analysis and is really only hypotheses generating With regards to tolerability 1) RCTs in general don’t show that the adverse effects are higher in the statin group compared to placebo - however the collection and reporting of adverse effects in all trials is at best weak 2) enough people complain of muscle aches while on statins that it likely is a real issue but it is really hard to put a number to the incidence Hope the above is clear enough. Just wondering what you think specifically about these points. James On Oct 22, 2018, at 2:53 PM, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: -this is an old debate -the key is the frequency and severity of the adverse effects Statins for primary prevention and serious adverse events http://www.cmaj.ca/content/184/7/791.1 -but of course, it is easy to find studies pushing for the classical position: Statins for the primary prevention of cardiovascular disease https://www.bmj.com/content/348/bmj.g280 Statins for Prevention of Cardiovascular Disease in AdultsEvidence Report and Systematic Review for the US Preventive Services Task Force https://jamanetwork.com/journals/jama/fullarticle/2584057 -i have sent three links, this morning, and the third one is a critc of the previous ones Behind the headlines. "Controversial report claims there's no link between 'bad cholesterol' and heart disease," "Bad cholesterol 'helps you live longer'," Crítica a "el colesterol malo ayuda a vivir más. Lo que hay detrás de un titular. https://www.nhs.uk/news/heart-and-lungs/study-says-theres-no-link-between-cholesterol-and-heart-disease/ -un saludo juan gérvas @JuanGrvas El lun., 22 oct. 2018 a las 19:24, Kev Hopayian (<[log in to unmask]<mailto:[log in to unmask]>>) escribió: What I take away from this is that in the elderly, cholesterol levels have poorer predictive value for primary events and less or no benefit in primary prevention. Hardly surprising, because as you get older, age becomes a stronger predictor. On 22 Oct 2018, at 15:41, Juan Gérvas <[log in to unmask]<mailto:[log in to unmask]>> wrote: Cholesterol LDL-C does not cause and it is not associated with cardiovascular disease. Do not use statins. El colesterol (ni "el malo", LDL) ni causa ni está asociado a enfermedad coronaria. No emplee estatinas. [if you have problems, ask me directly the PDF, for personal use] https://www.ncbi.nlm.nih.gov/pubmed/30198808 Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. En mayores de 60 años, menor mortalidad con colesterol "malo" (LDL) más alto. https://bmjopen.bmj.com/content/6/6/e010401.full Behind the headlines. "Controversial report claims there's no link between 'bad cholesterol' and heart disease," "Bad cholesterol 'helps you live longer'," Crítica a "el colesterol malo ayuda a vivir más. Lo que hay detrás de un titular. https://www.nhs.uk/news/heart-and-lungs/study-says-theres-no-link-between-cholesterol-and-heart-disease/ -un saludo juan gérvas @JuanGrvas ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 -- New Book by Owen Dempsey: Anticipation and Medicine: A Critical Analysis of the Science, Praxis and Perversion of Evidence Based Healthcare<https://www.taylorfrancis.com/books/9781351374866> Blog: https://myownprivatemedicine.com/ -- New Book by Owen Dempsey: Anticipation and Medicine: A Critical Analysis of the Science, Praxis and Perversion of Evidence Based Healthcare<https://www.taylorfrancis.com/books/9781351374866> Blog: https://myownprivatemedicine.com/ -- New Book by Owen Dempsey: Anticipation and Medicine: A Critical Analysis of the Science, Praxis and Perversion of Evidence Based Healthcare<https://www.taylorfrancis.com/books/9781351374866> Blog: https://myownprivatemedicine.com/ ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ *SECURITY/CONFIDENTIALITY WARNING: This message and any attachments are intended solely for the individual or entity to which they are addressed. This communication may contain information that is privileged, confidential, or exempt from disclosure under applicable law (e.g., personal health information, research data, financial information). Because this e-mail has been sent without encryption, individuals other than the intended recipient may be able to view the information, forward it to others or tamper with the information without the knowledge or consent of the sender. If you are not the intended recipient, or the employee or person responsible for delivering the message to the intended recipient, any dissemination, distribution or copying of the communication is strictly prohibited. If you received the communication in error, please notify the sender immediately by replying to this message and deleting the message and any accompanying files from your system. If, due to the security risks, you do not wish to receive further communications via e-mail, please reply to this message and inform the sender that you do not wish to receive further e-mail from the sender. (LCP301) ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 -- New Book by Owen Dempsey: Anticipation and Medicine: A Critical Analysis of the Science, Praxis and Perversion of Evidence Based Healthcare<https://www.taylorfrancis.com/books/9781351374866> Blog: https://myownprivatemedicine.com/ ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 <Risk Prediction models II External validation, model updating and impact assessment.pdf> ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 -- [https://docs.google.com/uc?export=download&id=1trbHzQEVu-S4vRoFrTrcBnSI03CvAkIH&revid=0B6u0lXR-VvCVZTgyWmQxaXFXQk5BYmY3b0FSN2NIaWc0cU9ZPQ] New Book by Owen Dempsey: Anticipation and Medicine: A Critical Analysis of the Science, Praxis and Perversion of Evidence Based Healthcare<https://www.taylorfrancis.com/books/9781351374866> Blog: https://myownprivatemedicine.com/ ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 -------------------------------------------------------------------- Prifysgol Aberystwyth www.aber.ac.uk Prifysgol y Flwyddyn ar gyfer Ansawdd Dysgu - The Times & The Sunday Times 2019. Aberystwyth University www.aber.ac.uk University of the Year for Teaching Quality - The Times & The Sunday Times 2019. ________________________________ To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1 ######################################################################## To unsubscribe from the EVIDENCE-BASED-HEALTH list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/webadmin?SUBED1=EVIDENCE-BASED-HEALTH&A=1