Category Archives: Healthcare

What the Tamiflu saga tells us about drug trials and big pharma

We have been subscribers to the All Trials network since founded by physician Ben Goldacre in Jan 2013. The mission statement is simple “All Trials Registered | All Results Reported”. The above-captioned article by Dr. Goldacre will make it clear why this initiative is so important:

Today we found out that Tamiflu doesn’t work so well after all. Roche, the drug company behind it, withheld vital information on its clinical trials for half a decade, but the Cochrane Collaboration, a global not-for-profit organisation of 14,000 academics, finally obtained all the information. Putting the evidence together, it has found that Tamiflu has little or no impact on complications of flu infection, such as pneumonia.

That is a scandal because the UK government spent £0.5bn stockpiling this drug in the hope that it would help prevent serious side-effects from flu infection. But the bigger scandal is that Roche broke no law by withholding vital information on how well its drug works. In fact, the methods and results of clinical trials on the drugs we use today are still routinely and legally being withheld from doctors, researchers and patients. It is simple bad luck for Roche that Tamiflu became, arbitrarily, the poster child for the missing-data story.

And it is a great poster child. The battle over Tamiflu perfectly illustrates the need for full transparency around clinical trials, the importance of access to obscure documentation, and the failure of the regulatory system. Crucially, it is also an illustration of how science, at its best, is built on transparency and openness to criticism, because the saga of the Cochrane Tamiflu review began with a simple online comment.

Tamiflu being made by Roche

 

(…snip…)

This is a pivotal moment in the history of medicine. Trials transparency is finally on the agenda, and this may be our only opportunity to fix it in a decade. We cannot make informed decisions about which treatment is best while information about clinical trials is routinely and legally withheld from doctors, researchers, and patients. Anyone who stands in the way of transparency is exposing patients to avoidable harm. We need regulators, legislators, and professional bodies to demand full transparency. We need clear audit on what information is missing, and who is withholding it.

Finally, more than anything – because culture shift will be as powerful as legislation – we need to do something even more difficult. We need to praise, encourage, and support the companies and individuals who are beginning to do the right thing. This now includes Roche. And so, paradoxically, after everything you have read above, with the outrage fresh in your mind, on the day when it feels harder than any other, I hope you will join me in saying: Bravo, Roche. Now let’s do better.

• Ben Goldacre is a doctor and the author of Bad Pharma.

You can help the All Trials mission. Join and sign the petition here. Spread the word, lean on your politicians, get involved.

Will Obama Ever Enforce His Health Law?

Megan McArdle's analysis and outlook has been accurate so far. She is increasingly pessimistic:

This is President Obama’s signature legislative achievement, the program for which he will be remembered. And he doesn’t have the courage to defend it, even when he is no longer facing re-election. If he won’t stand up for the hard choices his law requires, he can’t think that anyone else will either.

Megan's Intelligence Squared debate was excellent: Resolved: Obamacare Is Now Beyond Rescue.

 

The Trouble With ‘Scientific’ Research Today: A Lot That’s Published Is Junk

A number of empirical studies show that 80-90% of the claims coming from supposedly scientific studies in major journals fail to replicate.

Henry I. Miller surveys the wreckage of sloppy medical research.

…Another worrisome trend is the increasing publication of the results of flawed “advocacy research” that is actually designed to give a false result that provides propaganda value for activists and can be cited long after the findings have been discredited.

Dr. Miller is referring to the Gilles-Eric Séralini scandal:

(Séralini has made a specialty of methodologically flawed, irrelevant, uninterpretable — but over-interpreted — experiments intended to demonstrate harm from genetically engineered plants and the herbicide glyphosate in various highly contrived scenarios.)

Megan McArdle asks: “Where have all the uninsured gone?”

So far Obamacare has signed up roughly 15% of the 5 million uninsured that were used to justify the ACA. Megan puzzles over what this means:

(…) You’d expect the early numbers to be somewhat weighted toward the previously insured, who probably want to maintain continuous coverage. Still, this is a fairly wild skew, and it leaves us with a burning question: Where are the uninsured? Did hardly any of them want coverage beginning Jan. 1?
(…)
Maybe they were buying insurance directly from the insurance companies. But industry expert Bob Laszewski seems to say no, that’s not the case: “This is consistent with anecdotal reports from insurers I have talked to that are seeing very little net growth in their overall individual and small group markets as of January 1.”

That leaves us with two possibilities: First, would-be applicants may simply be waiting until March. They’ve gone without insurance a long time; why not wait a few more months and save on premiums?

The second possibility is more troubling: There may be something seriously wrong with our understanding of who the uninsured are, and what they are willing and able to buy in the way of insurance. I don’t know exactly what the fault may be in our understanding. But if the numbers stay this low, I’d say we need to reassess the state of our knowledge about the uninsured — and the vast program we created to cover them.

 

Metastatic cancer cells implode on protein contact

By attaching a cancer-killer protein to white blood cells, Cornell biomedical engineers have demonstrated the annihilation of metastasizing cancer cells traveling throughout the bloodstream.

The study, “TRAIL-Coated Leukocytes that Kill Cancer Cells in the Circulation,” was published online the week of Jan. 6 in the journal Proceedings of the National Academy of Sciences.

“These circulating cancer cells are doomed,” said Michael King, Cornell professor of biomedical engineering and the study’s senior author. “About 90 percent of cancer deaths are related to metastases, but now we’ve found a way to dispatch an army of killer white blood cells that cause apoptosis – the cancer cell’s own death – obliterating them from the bloodstream. When surrounded by these guys, it becomes nearly impossible for the cancer cell to escape.”

That is from the Cornell press release. I sure hope these results can be replicated. How difficult is the technique?

 

Re-Examining the FDA Antibiotics Decision: Banning Growth Promoters Won’t Be Enough

Denmark weaner pigs experience

Chart via Hagan Vigre, Danish Technical University, 2009

Further to the Denmark experience, Maryn McKenna has a new essay at Wired

The object lesson in changing antibiotic patterns is Denmark, which in 2000 made farm antibiotics prescription-only, and banned nontherapeutic uses altogether. It’s often pointed out, on the ag side, that Denmark had an increase in deaths among weaner pigs immediately after that ban was rolled out; but within 3 years, weaner pig survival improved and returned to where it had been before the ban.

What reversed the trend was Danish farmers’ understanding that it wasn’t enough just to remove antibiotics from meat production. What was necessary was to change the conditions in which meat animals were raised, so that the welfare threats which the antibiotics had addressed no longer existed.

That seems to me to be the lesson that meat production in America needs to learn, if the FDA’s intention to remove growth promoters is going to be meaningful. Simply reducing antibiotic use (if that does indeed happen) isn’t adequate; by itself, it may even be a threat to welfare. Changing the livestock practices that made antibiotic use necessary will improve animal and human health both.


How to protect effective antibiotics: a conversation with Doc Ricky

MRSA

I believe that the rapid spread of antibiotic resistance should be recognized as an urgent public health priority – possibly the #1 priority. E.g., CRE [1].

After reading Betsy McCaughey [2] “U.S. Lacks Will to Fight Superbugs” [3] I tweeted the citation for her op-ed

CRE the “nightmare bacteria”: U.S. Lacks Will to Fight Superbugs j.mp/1au0EbR

Shortly Doc Ricky replied:

@stevedarden I’m kind of perplexed by the media repetition of “fighting superbugs” – what do ppl expect anyway? Some secret weapon?

What an excellent framing question! I replied with some suggestions:

  1. Transparency of hospital performance on sanitation standards.
  2. No excuses policy on resistance cases e.g. Israel
  3. Strict limitation of agriculture use to disease, no routine NTA dosing
  4. Transparency on physician prescribing by doctor

Shortly Doc Ricky replied:

“@drricky: @stevedarden but problem is most of these are preventative, what is expected when MDR {Multi Drug Resistance} is detected?”

I replied over several tweets: By #2. what I meant is that the CDC publishes “best practice” on procedures to execute upon every identified case of MDR[4]- beginning with effective quarantine and decontamination. The “best practice” level of response is mandated to be the minimum response. It should be the top priority of the hospital to eliminate the detected microbe from the institution. I appreciate that is a statistical goal, as we have no way to validate that “we killed it”.

For examples of such best practices consider the 2011 NIH Clinical Center response to a CRE outbreak [5], and of Israel 2006 (from Betsy McCaughey):

When CRE invaded Israel’s hospitals in 2006, public health authorities launched a military-style campaign requiring reports from all hospitals, which were ordered to test patients and undergo rigorous cleaning efforts. This reduced CRE by 70 percent in one year. Israeli researchers just announced a drug that may protect patients exposed to CRE from becoming infected.

My personal bias is that regulation is a blunt and ineffective tool in complex, fast-changing domains like this one. My question: How to incentivize hospitals to succeed?

Suggestion: first try transparency. E.g., if the Johns Hopkins data, such as MDR cases, hand hygiene and infection-control scores are published on the web every month – that is a powerful incentive to improve – to be ranked among the very best institutions globally.

Meanwhile Doc Ricky tweeted a critique of my first try on agriculture:

@stevedarden The agriculture issue is more nuanced than that, after all, how does one exactly limit the use?

Exactly:

@drricky Legislating detailed Rx rules not practical. How about transparency of farm usage per animal-KG? Is public shame effective?

I am thinking of the Denmark experience beginning 1999 where they succeeded to eliminate NTA use in agriculture. See my 2010 Denmark: results of stopping NTA (non-therapeutic antimicrobials)

Doc Ricky moves the discussion to the next level, biology:

@stevedarden only skirts around the real problem, which is biology. We culture animals with similar physiology to ours

The microbes shared by humans and pigs, chickens, beef are why we are so concerned about agricultural applications of antibiotics. Agriculture uses roughly 80% of the antibiotics effective in the human population – but in vastly larger quantities. If we were all vegetarians that would eliminate the whole worry about agriculture.

Doc Ricky is truly the expert in this topic – I’m looking forward to learning from him. We agreed to shift the conversation from Twitter to a long-form-friendly fora.

@stevedarden clearly a complicated topic, and hope you’ll continue to discuss.

NOTES:


  1. The CDC on CRE Carbapenem-Resistant Enterobacteriaceae.  ↩

  2. Betsy McCaughey founder of Committee to Reduce Infection Deaths  ↩

  3.  (…snip…) CRE was first uncovered in North Carolina in 1999. By 2008, it had spread to 24 states and was “routinely” seen in certain New York and New Jersey hospitals. But hospitals kept quiet. Now it’s in at least 43 states.
    (…snip…) Two months ago at a press conference, CDC Director Thomas Frieden dubbed CRE the “nightmare bacteria,” warning that “without urgent action now,” superbugs like CRE will prevent patients from getting joint replacements, cancer therapy and other treatments. The risk of incurable infections will make these treatments too dangerous. Yet, where’s the urgent action?
    The CDC doesn’t even have accurate data on how many CRE infections are occurring and where, because according to the director of the CDC’s Office of Antimicrobial Resistance, Steven Solomon, the government agency has never reached out to state officials to make CRE a reportable disease. Only 12 states require hospitals to report cases. Astoundingly, New York State did not require reports until July 2013, despite CRE menacing some of its hospitals for a decade.  ↩

  4. I am using the shorthand MDR to represent all the emerging multi-drug resistant microbes.  ↩

  5. This is what happened at the National Institutes of Health Clinical Center in Maryland in 2011. A 43-year-old woman known to have CRE was admitted from a New York City hospital. The NIH treated her, using CDC infection-control precautions, but three weeks later, a male cancer patient who had had no contact with her came down with CRE. Week after week, more and more patients contracted the infection introduced by the New York woman. Six of those patients ultimately died, one of whom was a 16-year-old boy. To stop the outbreak, NIH investigators double-cleaned rooms with bleach and misted hydrogen peroxide in measures far beyond what the CDC recommends.  ↩

John Cochrane on portable health insurance

This piece by Tyler Cowen on John Cochrane on portable health insurance is so good I'll just quote the whole thing:

The entire Op-Ed is interesting and noteworthy, but the part on health insurance is perhaps the cutting edge of the piece analytically:

Health insurance should be individual, portable across jobs, states and providers; lifelong and guaranteed-renewable, meaning you have the right to continue with no unexpected increase in premiums if you get sick. Insurance should protect wealth against large, unforeseen, necessary expenses, rather than be a wildly inefficient payment plan for routine expenses.People want to buy this insurance, and companies want to sell it. It would be far cheaper, and would solve the pre-existing conditions problem. We do not have such health insurance only because it was regulated out of existence. Businesses cannot establish or contribute to portable individual policies, or employees would have to pay taxes. So businesses only offer group plans. Knowing they will abandon individual insurance when they get a job, and without cross-state portability, there is little reason for young people to invest in lifelong, portable health insurance. Mandated coverage, pressure against full risk rating, and a dysfunctional cash market did the rest.Rather than a mandate for employer-based groups, we should transition to fully individual-based health insurance. Allow national individual insurance offered and sold to anyone, anywhere, without the tangled mess of state mandates and regulations. Allow employers to contribute to individual insurance at least on an even basis with group plans. Current group plans can convert to individual plans, at once or as people leave. Since all members in a group convert, there is no adverse selection of sicker people.

I suppose my worry is this. As individuals age, they will become greater health risks and that will hold even if Cochrane keeps Medicare going. That means a higher price for their individual portable insurance. It is not clear to me under what conditions premia can be raised legally (what does “unexpected increase” mean?), but it seems the result is much higher premia for sick people, or legally-mandated low premia, but then providers will restrict access and lower the quality of care, as another means of raising the price of course. Contractually speaking, price is verifiable but quality of care is not. The overall problem is not one of “adverse selection” but rather simply that the good information of the suppliers means that insurance is hard to sell at all for many conditions.

I do understand the option of letting the premia rise, and selling insurance against that event too, and maybe that could work. Still, it is surprising how many insurance markets don’t really blossom even if it seems they would make economic sense. Just ask Robert Shiller or look at the earlier history of failed CPI futures. I’d like to experiment with Cochrane’s idea, which I think has real promise, but on a trial basis first. The question is what such a trial might actually mean, and who would be willing to give up their current arrangements to make such an experiment possible. If the recent Obamacare reactions show anything, it is that status quo bias is getting stronger all the time in matters of health care.

The Affordable Care Act perpetuates a myth of health insurance

Is the Affordable Care Act perpetuating a myth? Yes according to physician Luis Collar (who is also a novelist, the author of A Quiet Death). Dr. Collar outlines very nicely why “health insurance” as practiced in America is a very Bad Idea. Since it’s origins as a pathway for employers to get around FDR’s wage fixing, these contracts have been shaped by their special tax treatment. Since the employer-paid coverage is not taxed as income to the employee it has been used as a competitive hiring tool for over sixty years. It is like the Zombies, very hard to kill.

The bottom line is the ACA, aka Obamacare, was formulated to satisfy progressive backers of the Obama campaign. The design of ACA carefully avoided addressing any of the real and serious structural defects of the American insurance scheme:

  1. The tax exemption for employer-paid coverage
  2. The lack of a national competitive market
  3. The bundling of pre-paid routine care with catastrophic insurance coverage
  4. The high administrative costs of erecting a whole system that intermediates between consumer and provider
  5. The complete isolation of the consumer from knowledge of pricing, and largely from any knowledge of the quality of services provided.

I could go on, but Dr. Collar does such a nice job I’ll just quote these excerpts: 

Whenever a discussion of health care policy is initiated, the importance of health insurance, of extending coverage, takes center stage. The need for insurance quickly becomes an undeniable truth, a universal imperative. And we never seem to question this premise enough before getting more patients fitted with shiny, new policies. This was precisely the case with the Affordable Care Act. But where is the evidence insurance plays any role in improving anyone’s health? Why is it assumed more coverage is always the answer, particularly for routine care? I would argue it is little more than a myth, one found nowhere else in our collective understanding of insurance.

Let’s consider our experience with insurance in other areas of our lives. In most states, it’s mandatory for drivers to carry automobile insurance. But it doesn’t reduce the incidence of accidents or extend the life of a vehicle, nor does it cover oil changes, car washes, flat tires, or any other form of maintenance or unfortunate mechanical reality. Similarly, homeowners insurance doesn’t cover the cost of repairs when your kids put a hole in the wall, the price of having your gutters cleaned, or the removal of mold due to leaky pipes or unsealed windows.

Why, then, do we expect health insurance to function any differently? There is no compelling evidence that insurance improves outcomes. In fact, of the few studies conducted, most have either failed to control for known determinants of health or shown, at best, a very tenuous relationship between the two. Access to health care matters, but we mistakenly assume more insurance is the best way to increase access. We believe coverage for routine medical care, for everything from checkups to preventive care procedures, improves our nation’s health. It does not; it only appears to because of numerous confounding variables.

What is known, however, is the total amount of money available for health care, generally some large percentage of our GDP. That number is static at any given time and cannot be magically increased. In fact, by definition, relegating any aspect of health care to insurance industry jurisdiction necessarily decreases the funds available at the bedside. These companies must extract a profit; that’s how capitalism works. Moreover, whenever the scope of coverage is increased, patients and physicians give up more control as to the nature, timing, and extent of the routine care provided.

All insurance, even health insurance, should be procured to protect one’s financial interests against catastrophic, unforeseen events. Engaging it for routine activities, including all but the most costly drug therapies and procedures, serves only to dilute valuable resources and relinquish essential control. Thankfully, Healthcare.gov offers some high deductible plans that encourage direct payment for routine care, but many of them are also HMO-type plans, plans where third parties determine the routine care that is or isn’t covered.

Physicians must regain the authority to decide what routine care patients need. Despite the increasingly popular, one-size-fits-all algorithms of evidence-based medicine, it remains a fact that, even for those of similar age, sex, race, and socioeconomic background, every patient is unique. We have conceded that the future of pharmacology points to personalized medicine, to therapies tailored to an individual’s unique genetic composition, and yet we continue to assume that generic algorithms should govern what is best for a particular patient.

(…snip…) We need to embrace a system where health insurance is procured only to protect patients’ financial interests against catastrophic injury or illness and routine, less expensive health care services are paid for directly by patients. This would require a fundamental change in how individuals view their responsibility for their own health, an increased awareness that routine care must be budgeted for like any other household expense. But this shift would help control costs and empower patients to purchase competitively priced services from independent primary care physicians free of unnecessary administrative burdens. 

Read the whole thing.

The File Drawer Effect

This is not an academics-only esoteric debate. It is about whether new, effective drugs are released. It is about how accurate is our knowledge of reality. Here is astronomer Phil Plait quoted in this excellent essay on Survivorship Bias:

For far too long, studies that fizzled out or showed insignificant results have not been submitted for publication at the same level as studies that end up with positive results, or even worse, they’ve been rejected by prominent journals. Left unchecked, over time you end up with science journals that only present the survivors of the journal process – studies showing significance. Psychologists are calling it the File Drawer Effect. The studies that disprove or weaken the hypotheses of high-profile studies seem to get stuffed in the file drawer, so to speak. Many scientists are pushing for the widespread publication of replication, failure, and insignificance. Only then, they argue, will the science journals and the journalism that reports on them accurately describe the world being explored. Science above all will need to root out survivorship, but it won’t be easy. This particular bias is especially pernicious, said Plait, because it is almost invisible by definition. ”The only way you can spot it is to always ask: what am I missing? Is what I’m seeing all there is? What am I not seeing? Those are incredibly difficult questions to answer, and not always answerable. But if you don’t ask them, then by definition you can’t answer them.”

We subscribe to the AllTrails network – I can’t recommend their work highly enough. See also Publication bias in Wikipedia and All Results Journals.