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Archive for the ‘Ethics in Medicine’ Category

BMS, the original stent technology with meticulous metallurgy and design has been silently replaced by the drug eluting stent (DES) for over a decade. DES was introduced to bail out BMS from perceived high rates of  restenosis . It was a fundamental flaw, we failed to give due  weightage to the multiple variables like  operator expertise, lesion morphology, patient factors that determined the restenosis  rate .

There was never a single study done in large scale that compared a well deployed BMS with a poorly deployed BMS/ DES in terms of restenosis rate.This would have clearly quantified the technical component in the  restenosis rate that brought  pseduo -bad name for BMS in early days.

Without applying mind, wrong questions were asked and tested. No body could refute a “novel concept” , when some big names in industry  suggested  we must involve an anti cancer drug to prevent cell growth and neo-vascularisation  and hence restenosis. But , in reality  the technology of DES essentially complicated the metal behavior by adding a drug and drug adhesive agent(Polymer)  to the otherwise inert metal. Further , the , metallurgy  engineers had to restart / reduplicate from the scratch since we had  already well developed stent technology for BMS . The manipulation was  to add a drug to the metal.

The  irony of DES lies in the fact it Intentionally allowed to interfere /damage the endothelial healing and make the extended anti-platelet mandatory.  Still , DES was able to rule the world backed up by hyped data  with   bloated  reduction in restenosis rate. (Now we realise  the true benefits of DES  are nil  or at best marginal or even harmful in certain subsets of ACS .Read NORSTENT Trial linked below  )

Yes DES has a concern , but its not the drug you know !, 

Off late , since the polymer was  assumed as  culprit, variety of new generation stents with disposable /Non durable /Zero poylmer were developed. Still, polymer could not be proven as true culprit , some have started blaming  the drug again. Recently, It led to one famed DES based on Paclitaxel (which has a pride of place in the Land mark SYNTAX  study ) exited the human domain  with disgrace . (I wonder can  we conclude then SYNTAX study is also become invalid !)

This study done with over 9000 patients  concluded  like this  . . .

The DES industry was (is) so powerful it could easily shrug  the challenge of truth that came out briefly  in early 2000s when DES got hit with increased  acute complications.

Now, in 2016 NORSTENT study again showed us BMS is as good as DES in all walks of CAD.  Let us see what happens , still  its very unlikely mature cardiologists do not trust BMS.

*I have a belief  (Paranoid or not time will tell !) one of the reasons  DES are strongly promoted  is to sustain DAPT market alive and kicking for a long haul !

Scenerio  in India is frightening.

While the developed countries have DES usage rate around 65 % , India leads the world with DES constituting 95% (NIC registry 2017) of all deployed stents.What a way for a poor country  to  tackle CAD , which doesn’t even have prompt prehospital Aspirin for  bulk of their ACS patients, ready to waste  its resources in DES.

India , a country Infested with an unregulated health industry  became the perfect battle  ground for abusing the stents. With direct collusion with the large hospital managements the issue got exploded recently  .The Govt was compelled to come out with urgent restrictions and price control  in the use of stents.

Funny world this. World’s richest economies  are worried about the cost and want to phase out inappropriate therapy whenever possible, its absolute arrogance most of us feel shamed to keep BMS in their cathlab.

Final message

A  good metal based flexible ,trackable , thin struted  BMS should be the default choice for coronary stenting .( We used have one , now it vanished !)It avoids unnecessary prolonged DAPT .Most importantly one BMS costs 25 % of the cost of DES   . . . think of 4 critical proximal LAD lesions of a poor man can be fixed at the cost of one DES , that’s  definite way forward. Govt of India can pass another regulation in this regard. If you think  NORSTENT is NONSENSE  let us atleaset  insist for a large scale Indian  study for BMS /DES and  Cardiological society of India has much work to do !

Future for BMS  . . . looks bright !

While the  superiority  of DES is being increasingly questioned , the concept of surface modified BMS is being tested .This I believe is a face saving way to bring back the BMS in lieu of DES. There is a distinct  possibility of many of the new generation  DES going the BVS way in the near future.

Reference 

1.Hassan AK1, Bergheanu SC, Stijnen T, van der Hoeven .J Late stent malapposition risk is higher after drug-eluting stent compared with bare-metal stent implantation and associates with late stent thrombosis.Eur Heart 2010 May;31(10):1172-80. 

2.Zhang K1, Liu T, Li JA, Chen JY, Wang J,   Surface modification of implanted cardiovascular metal stents: from antithrombosis and antirestenosis to endothelialization.J Biomed Mater Res A. 2014 Feb;102(2):588-609.

3. https://www.pcronline.com/eurointervention/114th_issue/volume-12/number-17/350/ultra-hydrophilic-stent-platforms-promote-early-vascular-healing-and-minimise-late-tissue-response-a-potential-alternative-to-second-generation-drug-eluting-stents.

4.Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease NORSTENT Investigators N Engl J Med 2016; 375:1242-1252

Post-ample : Only For non believers  ( who think this article is near rubbish ) 

I am  very much  convinced DES should be superior  for the simple reason it elutes a drug and the whole world believes it works !

Do you know, what these drugs do, and what they are expected to do ! In this elegant study  by Hassan AKEur Heart J. 2010 May;31(10):1172-80.  Its proven with IVUS , DES is many fold likely to cause late stent apposition than BMS.( Thus carrying the risk long term )  Reason is simple , patchy and incomplete endothelisation on the luminal side and pathological metal vessel wall interface  in abluminal promoting late mal-apposition.

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PCI and coronary stents are revolutionary concepts  but they may not be  great life saving devices  . . . though the collective cardiology wisdom may seem to suggest so !

stents-india

The ideal way to describe a stent could be “Its a metal coil , if inserted properly in certain population of severely obstructive forms coronary artery disease may save some lives in acute situations  or give relief to pain in non acute situations”

*While the true benefits for the patient population is unsure . . . it’s absolutely certain stents  confer highest  quality of life to the  manufacturers and their chain of associates including the Noble professionals !

sir-william-osler

I wonder , what would be his comment about ubiquitous stents that rule the current era !

Learnt cardiologist’s  will know the true life saving potential of these stents (In the way its been currently used ) Their conscience will also tell how Inappropriate and Indiscriminate usage of stents has possibly consumed more human lives that may even beat the number of lives saved .(Oh, Its wild, rude statement  friend!)

I sincerely believe the move by Government of India to control the stent price ( to enable all our countrymen to get it)  . . . as if  “stents are the only staple diet” for heart patients is ill-founded and dangerous .

What the Government may not be aware of  is  . . .This 45000 crore omnipresent stent  industry is playing havoc in the life of patients not only financially  but also biologically to harm their blood vessels.

It is near foolish to tackle the scourge of human beings -Atherosclerosis,   a diffuse medical disease with a lesion specific intervention .This is especially true when we want to tackle it in population based approach . Yes, some super rich and elite  get sophisticated stents thinking that they are privileged .Please understand  rich tend to suffer more  with technology. Often times non affordability is also a bliss for the poor .(Rubbish ,won’t agree  . . . Is it , will realise later !)

Who will tell this to our  policy makers ?

Never ape the private sector health care , states must have different priorities.There are Infinite number of studies that  very clearly reveal medical management and life style modification is the sure and successful way to tackle CAD.(I think I need not dwell into this as evidence is explicit .)

Meanwhile, let me give one example of  the futility of innovation and perils of premature release of half baked science .While one section of Industry is coming out with stents made up of exotic new metals , simultaneously other group is innovating and experimenting the exactly opposite , how to get rid of the metal ie bioreabsorable stents. Mind you, one of the latest generation stents was severely reprimanded in a Landmark trial ABSORB 2. Its a comical irony some of the hospitals and cardiologists  feel bad  to miss this red flagged stent that are taken out of their cath lab because of price cap. ( A pat for the Govt for this !)

Its a multi billion dollar Industry (Note : there is no pardon for Indian companies to exploit either !) trying to disseminate a commercially motivated concept intelligently including the stake holder Government in their loop. The move to liberalise stent usage is  most unfortunate thing  as the Govt has  inadvertently increased the risk of abuse .Let the new age Indian not be proud  about “Stent for all ” movement since the  Govt will ultimately  have to shell  out for this imperfect therapeutics through public insurance .

Final message 

Though capping the price of the stent by Government  do carry  some sense  . . . ultimately      I feel its a trap . It’s akin to let loose a dubious  modality in public domain within easy reach . Already the companies want to increase per capita metal consumption. That process will only get accelerated now.

The Government must realise there is an urgent &  broader issue to be addressed by health ministry.Its not only in cardiology but in all walks of health delivery system. How to prevent “contamination of  medical science by pseudo scientific intervention fueled by corporate greed ? They should start  sensitizing the young medical professionals in medical schools that will help the Noble profession remain Noble !

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This year’s Noble prize for economics was conferred  for Dr Angus Deaton  from Princeton,  for an unique revelation, that measurement errors in economic indices such as estimation of poverty and nutrition levels in society  is real and huge .

The crux of argument (My version )  could be , data collection errors , planning with that contaminated data , sets in a chain reaction , that sustain a flawed intellect in young researchers , which  ultimately leads to human beings becoming  victim to their own  data . While Deaton addressed this in economic issues,  one can guess how critical these errors could be , when  one deals with a  continuously variable  biological parameters .

Every day , medical professionals are confronted with  diverging data measured with dubious methods. Measuring health as quantifiable semi mathematical parameter itself is intrinsically flawed , unfortunately this is the only way we can do it as of now.

If  logical extrapolation is the accepted norm and poverty is the most prolific disease  of humanity  (coded in ICD by WHO) its obvious Deaton’s work will have tremendous impact on medical science than any  other field .

As a cardiologist ,I struggle to understand for the past 30 years  , why we need to work towards a goals of  reducing few mmhg of blood pressure  (or few mg of LDL ) in elderly population knowing fully well the evidence for which is  soft with questionable end points. It  appears some times comical , when healthy people who are not taking these medicines in poor countries  are labelled as medically deprived ! by certain non Governmental agencies.

Final message

With existence of people like Deaton , there seems to be light at the end of tunnel , (Hope we don’t create new tunnels) It is heartening , we are witnessing major innovations in the assessment of health outcome,efficiency and impact in recent rimes.. Let us hope some common sense would be infused over the complicated number science !

Reference

Here is an awesome piece of writing  by Reetika Khera an associate of Angus Deaton at  Princeton .(Reproduced with the courtesy of Of “The  Hindu ”  -From the open page,   on the significance  of  Nobel Economics this year 2015)

Angus Deaton, the winner of this year’s Nobel in economics, has contributed immensely to the understanding of poverty, prices, nutrition and well-being in India. His work has been guided by the belief that economic progress must lead to better lives for everyone.

Much of the work by Angus Deaton, the winner of this year’s Nobel Memorial Prize in Economic Sciences, has been focussed on measurement issues. He has questioned the quality of data collected in large surveys and suggested ways of improving the surveys. He has also thought very hard about how these data could or could not be used, how to reduce measurement errors, and what inferences one can, or cannot, draw from data that might suffer from measurement errors.

Boring as that may sound, it has ensured that economists pay attention to detail, and do the hard work that empirical analysis demands. Good data is fundamental to good economics.

One example of this is from India. His contribution to the understanding of price indices and relatedly, poverty estimation, has been very important. He has highlighted the problems with the computation of price indices in India and how these affect poverty estimation. His proposal to use prices implicit in the data collected by the National Sample Survey Office was implemented by the Suresh Tendulkar committee some years ago.

His book on these issues, The Analysis of Household Surveys, published in 1997, remains the best to learn about data issues. Along with poverty estimation, he has applied his deep understanding of several disciplines (ranging from biology to philosophy) to work on mortality, health, nutrition and well-being. In his latest book, The Great Escape: Health, Wealth and the Origins of Wellbeing Inequality, he generously acknowledges Amartya Sen’s influence on this aspect of work.

India-focussed work on poverty

Much of this body of work on nutrition in India (and elsewhere) has come since the 2000s. A large part of it is India-focussed, much of it co-authored with Jean Drèze. In 1999-2000, there was a lot of interest in the poverty estimates as these were the first post-liberalisation estimates. Supporters of liberalisation were keen to show that poverty had declined, and that its rate of decline had accelerated since liberalisation. Those against it were unwilling to accept this.

A change in the methodology for data collection between 1993-94 and 1999-2000 made a straightforward comparison between the two point estimates impossible. Deaton’s work (with Drèze) on comparable estimates disappointed both camps. They found that while the official claim that poverty had declined in the post-liberalisation period was true, the claim that there had been an acceleration in the rate of decline was not.

In 2009, Deaton and Drèze published a paper in the Economic and Political Weekly (EPW) on the nutrition situation in India which once again provoked economists on both sides of the ideological spectrum. On the one hand it led to a debate, in the same journal, with Utsa Patnaik — widely considered to be on the Left — who felt that the decline in calorie consumption was a symptom of rising poverty. They, however, pointed out that calorie intake was declining even at given levels of real per-capita expenditure, especially among the better-off households, and discussed other possible reasons for this pattern.

On the other hand, in 2013, Arvind Panagariya challenged a long-held understanding among economists and nutritionists about anthropometric outcomes. The argument was not so much about whether height is a good indicator of nutrition, human development and well-being. Panagariya’s thesis was that Indians are short, not because they are undernourished but because they are “genetically programmed to be so”. Deaton and his co-authors pointed out in their response, again in the EPW, that “all of his arguments about the role of genetics is residual: if we cannot think of anything else [we assume that] it must be genetics.”

These two debates are illustrative of Deaton’s careful analysis and unwavering honesty, his ability to separate his social commitments from what his meticulous data work suggests. Indeed, at a press conference at Princeton University just after the prize was announced, he said that sometimes his work leads him to “very uncomfortable” places.

Questioning the dominant trend

Another important part of his contribution has been to question dominant fashions in development economics. When “instrumental variables” were a popular tool to establish causality, he wrote “students no longer look for a thesis topic, but for an instrument”.

More recently, a new technique “randomised control trials” (RCTs) has taken development economics by storm. For some, RCTs are seen as the only form of evidence, disregarding not only other forms of quantitative evidence but also other forms of qualitative evidence. Deaton has been among the few voices to question our over-reliance on RCT experiments while that acknowledging it as a valid body of evidence.

“I argue that experiments have no special ability to produce more credible knowledge than other methods, and that actual experiments are frequently subject to practical problems that undermine any claims to statistical or epistemic superiority,” he said.

The “randomistas”, a term used by The Economist, have been influential in several states in India. The Government of Tamil Nadu has signed a Memorandum of Understanding (MoU) “to institutionalise an evidence-based approach to policymaking”. Some experiments have led to greater hardship for the poor — for example, delays in wage payments to National Rural Employment Guarantee Scheme (NREGS) workers — without any accountability for these adverse outcomes.

For Deaton, the problem is not with RCTs per se — some of his current work is on how to use RCTs — but rather with the view that it is the only form of evidence that matters or that it should be the only driver of policy decisions. He has his differences with arguments like that advocated by Abhijit Banerjee when he said that “the World Bank should cease to fund any activity, including presumably macro policy advice, that has not been previously subject to evaluation by an appropriate RCT.”

Advocate for a greater state role

Apart from claims of statistical or epistemic superiority, Deaton has questioned the divorce between policymaking and public discussion. His contribution has not only been as a rigorous economist, but equally as a public intellectual. He is a firm supporter of government action for social policy. Without being blind to the problems of governments in poorer countries, he forcefully argues for their greater accountability.

“The absence of state capacity — that is, of the services and protections that people in rich countries take for granted — is one of the major causes of poverty and deprivation around the world. Without effective states working with active and involved citizens, there is little chance for the growth that is needed to abolish global poverty,” he argued.

On the consequences of inequality, while some inequality can be a good thing, Deaton has argued that too much could potentially have negative consequences for us all.

He noted that:

“The very wealthy have little need for state-provided education or health care… They have even less reason to support health insurance for everyone, or to worry about the low quality of public schools that plagues much of the country…To worry about these consequences of extreme inequality has nothing to do with being envious of the rich and everything to do with the fear that rapidly growing top incomes are a threat to the well-being of everyone else.”

These messages are important because public debate in the past few years in India have tended to belittle various forms of public support through terms like ‘doles’, ‘freebies’, and ‘handouts’. Repetition succeeded in creating an impression — unsubstantiated by facts — that India has gone overboard in its social spending. We have witnessed strong rhetoric on evidence-based policymaking, combined with a resolute disregard for inconvenient facts. We need to engage with Deaton’s contributions very carefully.

(Reetika Khera teaches at IIT Delhi. She did her post-doctoral research at Princeton University under Angus Deaton.)

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