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I agree with Huw in that reduction through evidence base, clarity, and transparency adds quality of practice and therefore life. This platform would be a better foundation on which to rebuild values. If at present they are built on poor diagnostics that could change when this sector improves. `the example that comes to mind is mammography. If it was clear what the earlier diagnosis lead to and indeed how to diagnose in a standardized way that would bring about a change in values in my estimation. Best Amy From: "Huw Llewelyn [hul2]" <[log in to unmask]> Reply-To: "Huw Llewelyn [hul2]" <[log in to unmask]> Date: Thursday, October 11, 2012 1:45 PM To: <[log in to unmask]> Subject: Re: The causes and remedies of overdiagnosis and overtreatment Ben and Bill I fully accept what you both say about value judgments and society pushing for more. Personally, I would not call this over-diagnosis or over-treatment but personal choice and debate. However, you are quite correct about my aim being to reason in as accurate a way as possible. It is a failure to do this that I would describe as over and under-diagnosis¹ and over and under treatment¹. I would also like to see this being done in a sound transparent way that makes the work of doctors more rewarding and less stressful, minimising the risk of litigation and thus making full use of empathy and personal experience when advising patients. Best Huw From: Evidence based health (EBH) [[log in to unmask]] on behalf of Djulbegovic, Benjamin [[log in to unmask]] Sent: 11 October 2012 17:31 To: [log in to unmask] Subject: Re: The causes and remedies of overdiagnosis and overtreatment of course, Huw but because it ultimately involves values, it will require a broader societal discussion to get to the consensus. For example, at least in the US, physicians easier tolerate overtreatment than undertreatment (because of regret of comissions is typically lower than regret of omissions for all sorts of reasons including threat of litigation) ben From: Evidence based health (EBH) [[log in to unmask]] on behalf of Huw Llewelyn [hul2] [[log in to unmask]] Sent: Thursday, October 11, 2012 10:24 AM To: [log in to unmask] Subject: Re: The causes and remedies of overdiagnosis and overtreatment Ben and Richard I agree that it cannot be 'solved'! But do you agree that over-diagnosis and over-treatment could be REDUCED (all else: surrogates, values etc being equal) if we were to arrive at diagnostic and treatment indication criteria in an evidence-based way as I describe? Huw From: "Djulbegovic, Benjamin" <[log in to unmask]> Date: Thu, 11 Oct 2012 14:02:27 +0000 To: Huw Llewelyn [hul2]<[log in to unmask]> Cc: Lehman, Richard<[log in to unmask]>; [log in to unmask]<[log in to unmask]> Subject: Re: The causes and remedies of overdiagnosis and overtreatment Thanks, Huw Could not agree more- but again it illustrates my main point that this is a technically not solvable issue Ben Ps in my haste, I only now realized that in my example below there was a typo : NNH should have been 100 ( and not 1!). As we showed some time ago, action threshold =NNT/NNH ( if someone wants the paper, let me know) Sent from my iPhone (Please excuse typos & brevity) On Oct 11, 2012, at 9:01 AM, "Huw Llewelyn [hul2]" <[log in to unmask]> wrote: > Dear Ben and Richard > > The purpose of this example was to illustrate the general point that when > making decisions, the value¹ judgments are about outcomes that are yet to > happen and it is also important to assess the probability of the outcome > happening in a sensible way. I agree with your point that the value¹ > judgments that we attached to surrogate end points are very questionable. I > happened to have this data available that was suitable to illustrate a method > of calculating probabilities and making a point. > > I agree that there is a desperate need to conduct trials with symptomatic end > points that give us analogous information about outcome probabilities if we > are to minimise over-treatment and under-treatment. It would be naļve to > think that over-treatment and under-treatment can be eliminated completely. > For that we would need perfect tests that perfectly predict treatment > outcomes. However, we can improve things dramatically with more > thoughtfulness. > > In any case, the reality is that if a diabetic patient is labeled with > diabetic nephropathy¹ because of the surrogate marker of albuminuria > > 200mcg/24hours, they are going to be subjected to the hassle of attending even > more clinics, diets etc in addition to symptoms, so it may be worth taking a > tablet to reduce the probability of such extra hassle (as well as the more > remote possibility of dying with the symptoms of renal failure). The problem > is of course, that the patient will then probably die in some other way, which > might be more unpleasant. Ultimately we need unattainable endpoints that > consist of optimal lives and deaths. So, all outcomes have to be surrogate¹ > to some extent. > > I also don¹t think that we should apply alarming diagnostic labels e.g. > diabetes mellitus¹ (which means wasting away as a siphon) to anyone with no > symptoms but for example two fasting sugars of 7.1mmol/l in the same way as we > do to those with the misery of a full house of complications after many years > of severe illness. However, the current thoughtlessness of diagnostic labels > and the wooly thinking behind it will only be overcome if we estimate the > probability of outcomes in a sensible and as accurate a way as possible, > whether they are imperfect symptomatic or imperfect asymptomatic surrogate > outcomes. > > With best wishes > > Huw > > > > From: Djulbegovic, Benjamin [[log in to unmask]] > Sent: 11 October 2012 13:04 > To: Lehman, Richard; [log in to unmask]; Huw Llewelyn [hul2] > Subject: RE: The causes and remedies of overdiagnosis and overtreatment > > Dear Huw & Richard, > Thanks for starting this extremely interesting and important discussion. In > the final analysis, it does come to the issue what is most rational approach > to (medical) decision-making. Huw endorsed expected utility approach (EUT), > the only existing theory that satisfies all (statistical/mathematical) > criteria of rationality. According to EUT, for example, if NNT=10 and NNH=1, > you would then treat anyone if probability of developing diabetic nephropathy > is greater than 9%. Somehow, however, this would plainly indicate that we will > overtreat majority of patients. Iztok Hozo & I wrote a little piece > questioning this approach ³Will Insistence on Practicing Medicine According to > Expected Utility Theory Lead to an Increase in Diagnostic Testing?² > (attached), which complements the arguments Ash & I made in the piece quoted > below. > I believe that this is an important debate to have- looking to further > thoughts from you and others\ > Best > ben > > > > From: Evidence based health (EBH) > [mailto:[log in to unmask]] On Behalf Of Lehman, Richard > Sent: Thursday, October 11, 2012 7:46 AM > To: [log in to unmask] > Subject: Re: The causes and remedies of overdiagnosis and overtreatment > > > Dear Huw, > > You have actually given a beautiful illustration of Ben's point. > > It I am a patient with diabetes, why should I care whether I excrete albumin > in small quantities? There may be an observational, statistical relation > between albumin excretion and the development of end-stage renal failure, but > the latter remains a very remote risk for any individual patient with > so-called "diabetic nephropathy". I am not sure it is possible to derive a NNT > based on real evidence of ARBs preventing anything that any patient would > notice. We are extrapolating from a surrogate marker only. It is perfectly > possible to reduce albumin excretion and increase the risk of adverse events. > But because we don't have enough long-term evidence, we invent a bogeyman > diagnosis called "early diabetic nephropathy" and treat that as it it were a > clinical reality. > > So it all comes back to our values - treat the herd and hope to reduce renal > failure - or the patient's. The rot began when we measured her albumin > excretion. > > Richard > > > From: Evidence based health (EBH) [[log in to unmask]] on > behalf of Huw Llewelyn [hul2] [[log in to unmask]] > Sent: Thursday, October 11, 2012 6:44 AM > To: [log in to unmask] > Subject: Re: The causes and remedies of overdiagnosis and overtreatment > > Dear Ben > > I agree that values¹ attached to outcomes always have to be involved, but > these have to be multiplied by the probability of that outcome to give the > expected value¹. False positive and false negative results are created if > test results are dichotomised e.g. into high¹ or not high¹ etc. Doing this > results in less accurate probabilities however. This is illustrated with the > example below. > > The indication for treatment is often non-evidence based but some artificially > dichotomised result e.g. in diabetic microalbuminuria, an albumin excretion > rate of more than 20 µg/min - two standard deviations above the mean of the > healthy population. However, evidence suggests that introducing this cut-off > point causes errors because when compared to a non-angiotensin reducing agent > as control, treatment with an angiotensin receptor blocker does not reduce > nephropathy in normotensive patients with an albumin excretion rate of 20-40 > µg/min (about 30% of the currently treated population). > > Furthermore, an albumin excretion rate of 41 µg/min is abnormal¹, but the > number needed to treat with an angiotensin receptor blocker to stop one > patient at 41 µg/min getting diabetic nephropathy within two years is about > 100 (the probability of benefit is 1%). When this is used to calculate an > expected value¹, it would probably lead to a decision not to treat. However, > if the 'abnormal' rate is 60 µg/min, the number needed to treat is about 10 > (the probability of benefit = 10%) and the expected value¹ from treatment > would be higher, leading to a decision to treat. Thus, even if the test > result is in an abnormal¹ range, the actual value of the test results should > be used when choosing whether to treat when the 'expected values' are > calculated and then taken into account. > > This is why I think that accurate evidence-based diagnostic and treatment > indication criteria based on evidence-based probabilities are important. Also > combining System I and System II thinking appears to improve probabilities as > discussed previously. > > With best wishes > > Huw > > > > From: Evidence based health (EBH) [[log in to unmask]] on > behalf of Djulbegovic, Benjamin [[log in to unmask]] > Sent: 11 October 2012 04:01 > To: [log in to unmask] > Subject: Re: The causes and remedies of overdiagnosis and overtreatment > > I personally think that overdiagnosis and overtreatment is not solvable on > technical ground because it inevitably involves VALUES related to trade-offs > of false-positives vs. false-negatives. It is closely linked to indication & > prevention creep. > Ash Paul wrote a piece a year or so ago that discussed some of these issues > and may be of interest ( From Efficacy to Effectiveness in the Face of > Uncertainty > Indication Creep and Prevention > JAMA. 2011;305(19):2005-2006. doi:10.1001/jama.2011.650. > > Ben > > > On Oct 10, 2012, at 6:44 PM, "Huw Llewelyn [hul2]" <[log in to unmask]> wrote: >> >> Dear All >> >> Do you agree that over-diagnosis and over-treatment could be much reduced if >> we were to arrive at diagnostic and treatment indication criteria in an >> evidence-based way (as argued in the following 'rapid response' sent this >> week to the BMJ: http://www.bmj.com/content/345/bmj.e6684/rr/606818 )? >> >> Huw Llewelyn >> Aberystwyth University >> >>