A JAMA Press Briefing on CER, Helicopters and Time for Questions

This week the Journal of the American Medical Association, JAMA, held a media briefing on its current, Comparative Effectiveness Research (CER) theme issue. The event took place in the National Press Club. A doctor, upon entering that building, might do a double-take waiting for the elevator, curious that the journalists occupy the 13th floor – what’s absent in some hospitals.

CER is a big deal in medicine now. Dry as it is, it’s an investigative method that any doctor or health care maven, politician contemplating reform or, maybe, a patient would want to know. The gist of CER is that it exploits large data sets – like SEER data or Medicare billing records – to examine outcomes in huge numbers of people who’ve had one or another intervention. An advantage of CER is that results are more likely generalizable, i.e. applicable in the “real world.” A long-standing criticism of randomized trials – held by most doctors, and the FDA, as the gold standard for establishing efficacy of a drug or procedure – is that patients in research studies tend to get better, or at least more meticulous, clinical care.

The JAMA program began with an intro by Dr. Phil Fontanarosa, a senior editor and author of an editorial on CER, followed by 4 presentations. The subjects were, on paper, shockingly dull: on carboplatin and paclitaxel w/ and w/out bevacizumab (Avastin) in older patients with lung cancer; on survival in adults who receive helicopter vs. ground-based EMS service after major trauma; a comparison of side effects and mortality after prostate cancer treatment by 1 of 3 forms of radiation (conformal, IMRT, or proton therapy); and – to cap it off – a presentation on PCORI‘s priorities and research agenda.

I learned from each speaker. They brought life to the topics! Seriously, and the scene made me realize the value of meeting and hearing from the researchers, directly, in person. But, NTW, on ML today we’ll skip over the oncologist’s detailed report to the second story:

Dr. Adil Haider, a trauma surgeon at Johns Hopkins, spoke on helicopter-mediated saves of trauma patients. Totally cool stuff; I’d rate his talk “exotic” – this was as far removed from the kind of work I did on molecular receptors in cancer cells as I’ve ever heard at a medical or journalism meeting of any sort –

Haider indulged the audience, and grabbed my attention, with a bit of history:  HEMS, which stands for helicopter-EMS, goes back to the Korean War, like in M*A*S*H. The real-life surgeon-speaker at the JAMA news briefing played a music-replete video showing a person hit by a car and rescued by helicopter. While he and other trauma surgeons see value in HEMS, it’s costly and not necessarily better than GEMS (Ground-EMS). Helicopters tend to draw top nurses, and they deliver patients to Level I or II trauma centers, he said, all of which may favor survival and other, better outcomes after serious injury. Accidents happen; previous studies have questioned the helicopters’ benefit.

The problem is, there’s been no solid randomized trial of HEMS vs. GEMS, nor could there be. (Who’d want to get the slow pick-up with a lesser crew to a local trauma center?) So these investigators did a retrospective cohort study to see what happens when trauma victims 15 years and older are delivered by HEMS or GEMS. They used data from the National Trauma Data Bank (NTDB), which includes nearly 62,000 patients transported by helicopter and over 161,000 patients transported by ground between 2007 and 2009. They selected patients with ISS (Injury severity scores) above 15. They used a “clustering” method to control for differences among trauma centers, and otherwise adjusted for degrees of injury and other confounding variables.

“It’s interesting,” Haider said. “If you look at the unadjusted mortality, the HEMS patients do worse.” But when you control for ISS, you get a 16% increase in odds of survival if you’re taken by helicopter to a Level I trauma center. He referred to Table 3 in the paper.  This, indeed, shows a big difference between the “raw” and adjusted data.

In a supplemental video provided by JAMA (starting at 60 seconds in):

When you first look, across the board, you’ll see that actually more patients transported by helicopter, in terms of just the raw percentages, actually die.” – Dr. Samuel Galvagno (DO, PhD), the study’s first author.

The video immediately cuts to the senior author, Haider, who continues:

But when you do an analysis controlling for how severely these patients were injured, the chance of survival improves by about 30 percent, for those patients who are brought by helicopter…

Big picture:

What’s clear is that how investigators adjust or manipulate or clarify or frame or present data – you choose the verb – yields differing results. This capability doesn’t just pertain to data on trauma and helicopters. In many Big Data situations, researchers can cut information to impress whatever point they choose.

The report offers a case study of how researchers can use elaborate statistical methods to support a clinical decision in a way that few doctors who read the results are in a position to grasp, to know if the conclusions are valid, or not.

A concluding note –

I appreciated the time allotted for Q&A after the first 3 research presentations. There’s been recent, legitimate questioning of the value of medical conferences. This week’s session, sponsored by JAMA, reinforced to me the value of meeting study authors in person, and having the opportunity to question them about their findings. This is crucial, I know this from my prior experience in cancer research, when I didn’t ask enough hard questions of some colleagues, in public. For the future, at places like TEDMED – where I’ve heard there was no attempt to allow for Q&A – the audience’s concerns can reveal problems in theories, published data and, constructively, help researchers fill in those gaps, ultimately to bring better-quality information, from any sort of study, to light.

Related Posts:

The Outlier’s Message, and Evolutionary Science in Breast Cancer

This past week I read several attitude-altering articles about breast cancer.

Kathy Rich, as featured in ‘O’ Magazine

The first lesson, if I might call it that – in the way an oncologist can learn from variations in her patients’ pathology and clinical outcomes – comes from the case of Katherine Russell Rich, who died last week at the age of 56. As reported by Katherine O’Brien in the I Hate Breast Cancer Blog, Rich lived with metastatic BC (MBC) for 18 years. That’s phenomenal, was my first reaction to this news. The prognosis for MBC is said to be around 3 years, and Rich lived for 18 years beyond her tumor’s recurrence with stage IV disease.

As sad and unsatisfactory as this outcome may seem, and it is, Rich’s story offers hope for life beyond the 3 or 4 or 5 years some women with MBC pray, “ask” or otherwise bargain for, fingers-crossed…

As she detailed in an O article, Rich’s initial diagnosis came when she was 32 years old, in 1988. The Times, in an obituary, tells of her lumpectomy, chemo and radiation. In 1993 her cancer came back in bones including her spine. She had a bone marrow transplant, but the disease progressed. Ultimately, she coursed through various and some archaic hormone treatments.

Along the way, she lost or quit a job in publishing, or both, and traveled to India, and authored two books. In a 2010 first-person story about her case, she told of updating her status – of being alive – at Breastcancer.org each year. She wrote:

…I tell the women how deeply I believe there’s no such thing as false hope: all hope is valid, even for people like us, even when hope would no longer appear to be sensible.

Life itself isn’t sensible, I say. No one can say with ultimate authority what will happen — with cancer, with a job that appears shaky, with all reversed fortunes — so you may as well seize all glimmers that appear.

My take, as an oncologist and former clinician, is that patients sometimes surprise you. Hard to know which woman will respond to a non-targeted treatment, or even a drug like an estrogen modulator, without trying. And I wonder – and this is speculative, but maybe, likely, the two together – doctor and patient – worked together to see what worked in Rich’s case over nearly 2 decades, and what didn’t work.

A Bell Curve

If a drug helps, keep it going; if it hurts, stop. There are so many algorithms in medicine, and molecular tools, but maybe the bottom line is how the, one, your patient is doing.

Which leads me to another post, by Dr. David Gorski, a breast cancer surgeon and researcher who blogs as Orac – what once was imagined as a fabulously capable information processor, at Respectful Insolence. He describes how tough it can be to define, and thereby target or destroy, any individual patient’s breast tumor because the cancer cells are constantly changing. Within each woman’s tumor, an evolution-like process is ongoing, leading to selection of treatment-resistant cells. This is not news in oncology; the concept has been understood for years as it applies to “liquid” tumors like leukemia, as he points out.

In breast cancer, understanding the complexity of each case is more recent. Gorski considers a genetic analysis of 104 triple negative breast cancer (TNBC) cases presented at the recent AACR meeting and published last week in Nature:

“…The 59 scientists involved in this study expected to see similar gene profiles when they mapped on computer the genomes of 100 tumours.

But to their amazement they found no two genomes were similar, never mind the same. “Seeing these tumours at a molecular level has taught us we’re dealing with a continuum of different types of breast cancer here, not just one,” explains Steven Jones, co-author of this study.

…TNBC is not a single disease. In fact, even an individual TNBC tumor is not a single disease. Tumor cells evolve as they proliferate, so that the cells in them are genetically heterogeneous. The cells growing in one area of a tumor can and often do harbor markedly different genetic mutations from the cells growing in another part of the tumor…

The team found that each tumor displayed multiple “clonal genotypes,” suggesting that the cancer would have to be treated as multiple diseases, rather than a single entity.

So besides that there are distinct subtypes of breast cancer, those labeled as TNBC are diverse and contain variation within; each patient harbors sub-clones of malignant cells that, in principle, respond differently to treatment.

Orac, the fictional supercomputer (Wiki-Commons image)

Putting these links together –

The message from Katherine O’Brien, who lives with MBC and blogs about it, is that one outlier – like Katherine Russell Rich – can provide hope to other patients and, maybe, clues for scientists about why she lived for so long with metastatic BC. The message from Orac, a physician-scientist blogger, is how hard it is to pinpoint an individual breast tumor’s molecular aspects, because the disease is so mutable and diverse.

The problem, and this reflects evolution in my thinking over a long while, is that published data – the gold standard, what supports EBM – are largely limited to findings based on trials of groups. We understand now, better than we did 10 or 20 years ago, that each patient’s tumor is unique and can evolve over time, naturally or in response to therapy. Clinical trials, though rigorously planned and elaborately structured, are incredibly expensive and flip-floppy, disappointing overall.

What I’m thinking –

Algorithms – except in the broadest sense – may not offer the optimal approach to cancer treatment. Maybe the median doesn’t matter so much as we’d thought.

Here’s a ~retro idea: In 2012, maybe the ideal and most cost-effective oncology practice would blend low-tech observations – like findings on physical examination and how the patient’s feeling – with occasional, high-tech analyses – like markers for genetic drift within a tumor. If doctors are well-trained and non-robotic, in either the literal or figurative sense, and if they lack COIs regarding treatment decisions, they’d provide better, more effective and personalized treatments than what’s typically offered based on evidence reached through elaborate, costly clinical trials of many patients with similar but non-identical cancers.

All for now,

ES

Related Posts:

Why I Support Health Care Reform

One advantage of blogging is that I can share my ideas, directly, with people who find them interesting, provocative or otherwise read-worthy. So for those who are curious, here is my general view on health care reform (HCR) by any name, in 3 points:

First, we need it. The U.S. health care system doesn’t work. It doesn’t serve doctors. Good physicians are few and far between in some geographical regions, in primary care and in needed specialties (like oncology and geriatrics). It doesn’t serve people who might be patients, except if they happen to work for a generous employer that offers a good plan (few do), they are rich enough so they might spend thousands each year out-of-pocket and out-of-network, or they are most fortunate of all, having no serious medical problems to contend with or pay for.

Second, although I wholeheartedly support the Affordable Care Act, because it’s a step in the right direction, I don’t think the legislation goes far enough. We need a simpler, single-payer solution, as in a national health care program, Medicare-style, for all. Why? Because the quasi-plan for state-based exchanges, each with competing offerings and not necessarily interpretable terms of coverage, is too complicated. There’s no reason to think a free market operating at the state level would match the public’s or many individuals’ medical needs. As long as each provider is trying to make a buck, or a billion, it won’t put patients’ access to good care first. Besides, there’ll be administrative costs embedded in each exchange that we could live better without. As for private insurers, well, I couldn’t care less about the well-being of those companies or their executives’ incomes.

Profit is not what medical care is about, or should be about. What we need is a simple, national health plan, Europe-style, available to everyone, with minimal paperwork and, yes, limits to care.

Third point – on rationing.

Some of my readers may wonder how I, who support some costly components of good medical care, like providing breast cancer screening for middle-aged women and sometimes giving expensive drugs to people with illness, favor health care reform. New cancer meds cost around $100,000 year, more or less, as do innovative treatments for cystic fibrosis, inflammatory bowel disease, rheumatoid arthritis and other conditions. I don’t think the sane solution is abandoning expensive but life-saving and quality-of-life-improving treatments.

The hardest part of this debate and what’s so rarely discussed is the appropriate limits of medical treatment, not based on costs – which we can certainly afford if we pull back on administrative expenses of health care and insurers’ huge profits – but on factors like prognosis and age. So, for example, maybe a 45 year old man should get a liver transplant ahead of an 80 year old man. Screening for breast cancer, if it is valuable as I think it is, should perhaps be limited to younger women, maybe those less than 70 or 75, based on the potential for life-years saved. Maybe we shouldn’t assign ICU beds to individuals who are over 85, or 95, or 100 years old.

The real issue in HCR, if you ask me, is who would decide on these kinds of questions. That conversation’s barely begun, and I would like to participate in that…

Meanwhile, the Supreme Court is busy doing its thing, sorting out whether the Affordable Care Act is constitutional or not. I’m glad they’re on the case, so that they might find that it stands and we can move on and forward.

#Obamacare is right –

Related Posts:

Harsh Words, and Women’s Health at Risk

I’ll open with a confession –

Women’s health has never really been at the heart of ML. Your author has, historically, relegated subjects like normal menstruation, healthy pregnancy and reproduction and natural menopause to her gynecologist friends. Sure, I learned about the facts of life. I even studied them in med school and answered questions, some correctly, along the way. By now, I’ve lived through these real life-phases directly. But these topics never drew me. That’s changed now.

Women’s care – and lives, in effect – are jeopardized on three fronts:

First, on birth control. Last week the Senate narrowly tabled a move to limit insurers’ responsibility to cover contraception. The vote on the so-called “conscience” amendment was 51-48. What this tells us is that essentially half of that powerful group either agrees with limiting women’s access to birth control or sees it as dispensable in the context of political aims.

The very fact that the proposal reached the Senate floor is disturbing. Without access to birth control, women –  including teenagers, people with significant medical problems that can be exacerbated by pregnancy, those who can’t afford to feed another child, and some who are already troubled or otherwise might not be ready or prepared to have children – are much more likely to become pregnant. It shouldn’t take a doctor to articulate this obvious point, and I can’t understand why so many are silent on it, but since so few physicians and the AMA in particular hasn’t issued any statement on this, I’ll stick my neck out and say it clearly: Lack of contraception puts women and their conceivable future-kids at risk for health problems that could be avoided.

The language surrounding the amendment is problematic, besides. Who are the anti-birth control legislation-writers to imply that “conscience” is involved in withholding contraception, and not the other way around? It’s like the “pro-lifers” who’ve implied that the rest of us aren’t.

Second, on access to safe abortions. I respect that some people think it’s wrong to terminate a pregnancy. But I also know that plenty of women, especially young women, get pregnant who don’t want to be pregnant. Regardless of who’s “responsible” – and any reader of this blog knows I’m no sucker for finger-pointing and behavior blame games – the bottom line is that if abortions become out-of-reach, women will suffer hemorrhage, life-threatening infections, permanent infertility  and premature deaths.

Hard to know how many women had ill effects or died from botched abortions before January, 1973, when the Supreme Court issued its decision on Roe vs. Wade. Like most women of my generation, I know of those unfortunate outcomes only indirectly. Still, I can’t rid my brain of the scary, unclean place Natalie Wood visits with a wad of cash in the 1963 movie Love with the Proper Stranger, or the tragic outcome when actor Gael García Bernal takes his pregnant love to an abortionist in the film Crime of Padre Amaro, set a decade or so ago in Mexico. But the real scoop comes from older physicians and nurses, here and now. When I was in med school in the 1980s, they told me stories of women and girls showing up in the emergency room bleeding, pale… dead.

As outlined by editorialists and writers elsewhere, mergers of Catholic hospitals with other medical centers threaten to reduce or eliminate access to abortions in some rural areas. In states like Texas, the physical and emotional rigmarole to which pregnant women are subjected prior to an abortion – including mandatory listening to a description of the fetal organs and a discussion loaded make what might be a tough decision unbearable, especially if the woman lacks confidence.

Which leads me to the third point of vulnerability – that women should be able to obtain care without intimidation or emotional abuse.

When Rush Limbaugh spoke last week, he wasn’t just talking about one Georgetown Law student. He was speaking to and about millions of young women who are sexually active. He called them sluts and insinuated they are like prostitutes. Adding insult to verbal injury, he said he’d like to watch videos of the sex. You could say who cares, he’s just some right-winged showman blowing off steam and misogyny. But this is a man who speaks to conservative leaders and feeds ideas to many households in America. Scary that the Republican front-runners, men who would be President of the United States next year, didn’t call Rushbo out. Rather, they let it go. As they might your daughter’s health, or access to birth control, or to a safe abortion.

In this new climate of shame, it’s easy to imagine a girl in some communities might feel really, really bad about herself simply for being sexually active. Whether she’s 17 years in high school, or 21 years in college, or 25 and maybe a department store clerk – and possibly lonely or confused – she may be embarrassed to ask for birth control. The Scarlet C, Robert Walker aptly called it yesterday.

The paradox is that this kind of rough talk, posturing and in some states, puritanical law-making, make it more likely that a sexually active young woman will become pregnant. And if she does become so, now, she may delay seeing a doctor because she fears his or her moral judgment about her behavior. And that leads to less healthy outcomes, and more deaths – fetal and maternal.

This is a serious health issue. I wish more doctors would speak out about it.

ADVERTISEMENTS:

Related Posts:

Counterfeit Drugs, A New Concern for Patients

This week the FDA issued an alert about fake Avastin. The real drug is a Genentech-manufactured monoclonal antibody prescribed to some cancer patients. Counterfeit vials were sold and distributed to more than a dozen offices and medical treatment facilities in the U.S. This event, which seems to have affected a small number of patients and practices, should sound a big alarm.

Even the most empowered patient – one who’s read up on his drug regimen, and engaged with his physician about what and how much he wants to receive, and visited several doctors for second opinions and went on-line to discuss treatment options with other patients and possibly some experts – can’t know, for sure, exactly what’s in the bag attached to his IV pole.

Counterfeit Avastin (images from FDA)

Scary because patients are so vulnerable –

The problem is this. If you’re sick and really need care, at some point you have to trust that what you’re getting, whether it’s a dose of an antibiotic, or a hit of radiation to a bone met, or a drug thinner, is what it’s supposed to be. If vials are mislabeled, or machines wrongly calibrated, the error might be impossible to detect until side effects appear. If you’re getting a hoax of a cancer drug in combination with other chemo, and it might or might not work in your case, and its side effects – typically affecting just a small percent of recipients – are in a black box, it could be really hard to know you’re not getting the right stuff.

What this means for providers is that your patients are counting on you to dot the i’s. Be careful. Know your sources. Triple-check everything.

The bigger picture – and this falls into a pattern of a profit motive interfering with good care – is that pharmacists and doctors and nurses need time to do their work carefully. They need to get rest, so that they’re not working robotically, and so that they don’t assume that someone else has already checked what they haven’t. And whoever is buying medications or supplies for a medical center, let’s hope they’re not cutting shady deals.

This issue may be broader than is known, now. The ongoing chemo shortage might make a practice “hungry” for drugs. And with so many uninsured, some patients may seek treatments from less-than-reputable infusion givers. The black market, presumably, includes drugs besides Avastin.

If I were receiving an infusion today, like chemo or anesthesia or an infusion of an antibody for Crohn’s disease, I’d worry a little bit extra. I mean, who will check every single vial and label and box? Think of the average hospital patient, and how much stuff they receive in an ordinary day – including IV fluids that might be contaminated with bacteria.

It’s scary because of the loss of control. This circumstance might be inherent to being a patient – in being a true patient and not a “consumer.”

Related Posts:

73 Cents: A Film on Regina Holliday’s Work, and Patient Advocacy Through Art

Yesterday I took a field trip to meet Regina Holliday, an artist and patient advocate. She fielded questions after a screening of 73 Cents, a short film about why she painted a mural by that name in the days after her husband died with metastatic kidney cancer. He was 39 years old.

At the time of her husband Fred’s diagnosis, both she and her husband held several jobs but he lacked health insurance. In a video, Holliday describes how his diagnosis and care were delayed.

“73 Cents” refers to the price, per page, Holliday needed to pay to get a copy of her husband’s chart when he entered a new medical facility. According to the film, she was told she’d have to wait 21 days to get his records, even though he was acutely ill and dying. Now a widow with two young sons, she pushes for patients’ rights to access to their health  records and, more generally, for a patient-centered approach to medical care.

The film-makers’ point: The unreasonable price of the medical records, combined with the delay in receiving them, exemplifies unnecessary harms patients encounter in an outdated, disjointed health care system.

Holliday has several ongoing projects, including the Walking Gallery. In that, she represents health care stories on the backs of people’s jackets. The idea is to take the message of the mural – which is one patient’s story, and necessarily static – and take it further.

Related Posts:

Oh, No Methotrexate!

structure of MTX (PubChem; NCBI)

I was astonished to learn that methotrexate supplies are running short. This chemotherapy may soon be unavailable to patients who need it. And it’s not just kids with leukemia, as the Times story highlights effectively.

Methotrexate is an old, bread-and-butter cancer kind of drug, a basic ingredient in standard regimens for many tumor types. I’ve personally administered this medication to patients with breast cancer, lymphoma, leukemia, head and neck tumors, ovarian cancer, colon cancer and people whose tumor cells spread to the brain. Doctors prescribe this drug, also, in a few non-malignant conditions, like rheumatoid arthritis.

Methotrexate has been used in cancer wards for over 50 years. And like other beyond-patent meds, it’s become less profitable to manufacture MTX compared to much costlier new agents. Hard to perceive this shortage as anything but a tragedy – that the business of health care renders valuable, inexpensive drugs out of reach.

Related Posts:

NIH Sponsors New Website to Help Patients Understand Clinical Trials

This week the NIH launched a new website, NIH Clinical Research Trials and You. In a Feb 6 press release, NIH Director Dr. Francis S. Collins said “The ability to recruit the necessary number of volunteers is vital to carrying out clinical research.” The idea behind the website is to help patients understand how clinical research works, and what it’s like to participate.

The site offers a menu of “basics” about clinical trials, addressing topics like:

  1. What are clinical trials and why do people participate?
  2. What is clinical research?
  3. Who participates in clinical trials?
  4. What do I need to know if I am thinking about participating?
  5. What questions should I ask if offered a clinical trial?
  6. How am I protected?
  7. What happens after a clinical trial is completed?
  8. How does the outcome of clinical research make a difference?

There’s an imperfect glossary of terms, a selection of patients’ and investigators’ stories, information for kids in research, and other resources including a link to the clinical trials database:  ClinicalTrials.gov.

Related Posts:

Notes on Wendell Potter, and Why Companies Support the Individual Mandate

The current debate about the individual mandate reminded me to post this –

About a year ago, I had the opportunity to hear Wendell Potter, author of Deadly Spin – an insider’s sharp critique of the insurance industry, speak at a meeting of the New York Metropolitan Chapter of Physicians for a National Health Program. Despite the cold, dark winter night and midtown dreariness of the meeting location, the large lecture room was packed. I arrived well before Potter’s presentation but couldn’t get a copy of his book; they’d sold out.

The meeting was instructive: I got a sense of Potter’s personal story (he’s from Tennessee, and lived for a while in Appalachia), his previous career (he worked as a journalist, turned to marketing, eventually led PR for Cigna) and his perspective on how people in the health care industry use language to frame the debate on health care reform. Since 2009, when he left his position at Cigna, he writes and speaks critically about the insurance industry.

Potter made several points that clarified my understanding of the insurance companies’ support of the Patient Protection and Affordable Care Act, and why many business-minded sorts are adamant about the individual mandate component in the law.

Insurance companies can’t make a profit without the individual mandate unless they deny coverage to people with pre-existing conditions, he explained. ”Think about it,” he said. “If young and healthy people aren’t going to buy insurance, and insurance companies can’t refuse to cover those with pre-existing conditions, the companies would be responsible only for providing health care to people who choose insurance, including everyone who is sick.”

“Most Republicans who say they favor repeal are disingenuous in that,” he said. “They’re using a smoke screen tactic to persuade the public that they’re against the legislation, but really they support it,” he told. “The insurance companies need it to stay in business,” he added.

The new legislation will also serve most large providers of health care services. That’s because without reform,  more and more Americans will go without any insurance. “If you keep shifting the costs of health care to consumers, they won’t buy it,” he said. And without insurance, most people can’t afford all but the most essential medical services – if those.

So the individual mandate assures that the insurance industry can remain profitable. And it serves the health care industry by maximizing the number of healthy people who will participate in health care spending.

In other words (ES): The health care industry needs health care to be affordable to many “consumers.”

All for now –
—-

Related Posts:

NEJM Reports on 2 New Drugs for Hepatitis C

Last week’s NEJM delivered an intriguing, imperfect article on a new approach to treating hepatitis C (HCV). The paper’s careful title, Preliminary Study of Two Antiviral Agents for Hepatitis C Genotype 1, seems right. The analysis, with 17 authors listed, traces the response of 21 people with hepatitis C (HCV) who got two new anti-viral agents, with or without older drugs, in a clinical trial sponsored by Bristol-Meyers Squibb.

The 21 study participants all had chronic infection by HCV genotype 1, a strain that’s common in North America and relatively resistant to standard treatment. All subjects were between 18 and 70 years old, with a measurable level of HCV RNA in the blood, no evidence of cirrhosis, and no response to prior HCV treatment (according to criteria detailed in the paper). In the trial, 11 patients received a combination regimen of daclatasvir (60 mg once daily, by mouth) and asunaprevir (600 mg, twice daily by mouth) alone; the other 10 patients took the experimental drugs along with 2 older meds for HCV – Peginterferon (Pegasys, an injectible drug by Roche) and Ribavirin (Copegus, a pill, by Roche).

The main finding is that the 10 patients assigned to take 4 drugs all did strikingly well in terms of reducing detectable HCV in their blood over the course of 24 weeks. There was a dramatic response, also, in 4 of the 11 patients assigned to the new drugs only. An accompanying editorial highlighted the work as a Watershed Moment in the Treatment of Hepatitis C. The medical significance is that they’ve demonstrated proof of principle: by “hitting” a resistant HCV strain with multiple anti-viral drugs simultaneously, they could reduce it to undetectable levels.

The first question you have to ask about this report is why the NEJM – the most selective of medical journals – would publish findings of an exploratory analysis of two new pills paired with two older drugs for HCV. The best answer, probably, is that the virus infects some 4 million people in the U.S. and approximately 180 million people worldwide, according to the study authors. HCV can cause liver damage, cirrhosis, liver cancer (which is usually fatal) and, occasionally blood disorders.

The new drugs derive from some interesting science. This, maybe, also is a factor in why the article was published in the NEJMDaclatasvir (BMS-790052) blocks a viral protein, NS5A, that’s essential for HCV replication. The second new drug, asunaprevir (BMS-650032) inhibits a viral protease, NS3.

I have several concerns about this report. One is that the researchers screened 56 patients for possible registration but enrolled only 21 on the trial; according to a supplementary Figure 1, 35 potential subjects (over half) didn’t meet criteria for eligibility. This disparity makes any once-researcher wonder about bias in selecting patients for enrollment. If you’re a pharmaceutical company and want to show a new drug or combo is safe, you’re going to pick patients for a trial who are least likely to experience or display significant toxicity.

Toxicity seems like it could be problematic. Diarrhea, fatigue and headaches were common among the study subjects. Worrisome is that 6 patients (of 21, that would be 28.5% of those on the trial) had liver problems manifest by at least one enzyme (the ALT) rising over 3 times the normal limit.

Further complicating the picture is there’s no indication of how these new drugs mesh with the two drugs approved for HCV in 2011: Vic­trelis (boceprevir) and Incivek (telaprevir).

Given all these limitations, you might wonder about BMS’s influence at the Journal or, more likely, the manuscript’s peer reviewers. The 17 study authors, and the editorialist, separately, disclose a host of industry ties.

What I’m thinking, as much as I’m critical of this research work, is that this is probably the way of the future – smaller, pharma-funded studies of targeted new drugs in complicated combinations. Many will be authored by academics with ties to industry, if not put forth directly by company-employed researchers. These quick-and-promising studies in select patient groups will be routine. And while advocates push for rapid publication of new clinical research in patients with resistant, disabling diseases, it’ll be hard for physicians and patients to interpret these kinds of data.

So these particular findings may turn out to be true and life-saving, or not. The bigger concern is this: It would be helpful if the journals would take a really tough stance on full disclosure of authors and editors ties to industry. As Merrill Goozner has emphasized, the Physician Payment Sunshine Act – a small component of the 2010 HCR legislation – has important implications for academic medicine and reporting of clinical research studies.

Related Posts:

The ‘Journal’ Asks, Should Patients Have Identification Numbers?

Today’s Wall Street Journal includes a special Big Issues health care section. A post on their blog caught my attention: Should Patient Have Electronic Identification Numbers?

The idea is that people who use health care would each be assigned a universal patient identifier, or UPI. This unique number would link to a person’s health records. In principle it would facilitate transfer of a patient’s medical history between doctors, hospitals and, likely, insurance companies. There are arguments pro – mainly having to do with efficiency and patient safety; and against – mainly having to do with privacy.

My issue is that it reminds me of Auschwitz. But apart from that particular association, labeling people with numbers seems dehumanizing – what’s already a big negative in modern health care. I/we need to realize that already we have numbers. Most people have social security numbers. I have several hospital ID numbers and insurance company numbers.

As for privacy, that’s history, or an illusion. If someone wants to know something about almost any person here in the U.S, they can find it. We inhabit a grid.

The debate reminds me of when I was an oncology fellow, and I treated a woman from Central America who had breast cancer. After she underwent a biopsy at our hospital, I reviewed the slides with the pathologist and wrote orders and injected her with chemotherapy. For 15 years or so I followed her in the clinic, and at some point, maybe 5 years after her diagnosis, she told me that her name was not what I’d thought or what her chart said it was. She’d used a cousin’s name and insurance card to get the care she needed.

More recently, I was with a relative who had an MRI. Upon registering at the radiology facility, he had to show a state-issued picture ID besides his insurance card. The issue was clear: with some 50 million or so Americans uninsured, and others without the ready means to cover co-pays, some people are assuming other patients’ identities to get the care they want or need.

The costs to insurers and hospitals of patient identity fraud – what in some instances I might liken to a hungry person stealing a loaf of bread – may underlie this topic’s appearance in the WSJ.

Related Posts:

Regorafenib, an Experimental Pill Tested in Colon and Rectal Cancer Patients, on Conference Agenda

Tomorrow the American Society of Clinical Oncology* will host its 9th annual GI Cancers Symposium. Bloomberg and the LA Times have already reported findings of a paper, still in abstract form, to be presented on Saturday.

The drug of interest is regorafenib, a pill that loosely inhibits quite a few kinases – enzymes critical in cell signals that control growth of normal cells, tumors and blood vessels. The experimental med, manufactured by Bayer, is also known as BAY 73-4506. The new data emerge from an international, randomized Phase III trial that goes by a loaded acronym: CORRECT.

The study included 760 patients with advanced colon or rectal cancer whose tumor progressed after receiving standard treatments. Participants received either the study drug or BSC (best supportive care) and a placebo. According to the paper, BSC includes antibiotics, pain meds, radiation for bone mets, steroids and some other treatments. The median survival in patients who received the Regorafenib was 6.4 months, compared with 5.0 months in patients who got the placebo. This difference, of 1.4 months in the median, was statistically significant. The “disease control rate” – a term that warrants separate explanation – was 44% in the regorafenib group c/w 15% in the placebo group.

The most frequent high-grade toxicities reported so far include a skin reaction affecting patients’ hands and feet, fatigue, diarrhea, elevated bilirubin in the blood, and high blood pressure. (Question to ask the oncologist who’s presenting these data at the meeting – was the elevated bilirubin from liver damage or hemolysis? With all the $millions spent on this trial, surely someone’s followed up on that detail.)

The language of the report and investigators’ comments are reminiscent of some regarding Avastin for advanced breast cancer. According to a media release: “…a subset of patients in the trial have responded particularly well to regorafenib, continuing to have stable disease for a relatively long time; research is ongoing to find ways to identify these individuals.” There are no biomarkers known to check for Regorafenib responsiveness.

What’s odd is that, according to the abstract, # LBA385, all patients entered the study between May, 2010 and March, 2011. This means some subjects were evaluated for less than a year, and the longest observation period for any patient on the trial is 20 months. Seems early to draw meaningful conclusions about the long-term toxicity and possible benefits of a cancer drug, especially for tumor types, like colorectal cancer, that don’t generally grow fast (c/w a condition like acute leukemia).

The list of investigators’ disclosures regarding ties to industry is too long to post here. You can find them at the tail end of the release. The FDA has assigned Fast Track status to this drug, according to Bayer.

*I am an ASCO member.

—-

Related Posts:

Quote of the Day: On Death Panels and the Insurance Industry, From Dr. Donald Berwick

Dr. Donald Berwick left his position last week as head of CMS. He said this, as quoted in the WSJ’s Washington Wire, yesterday:

“Maybe a real death panel is a group of people who tell health care insurers that is it OK to take insurance away from people because they are sick or are at risk for becoming sick.”

I couldn’t agree with him more.

All for this week,

ES

Related Posts:

A Good Personal Health Record is Hard to Find

Over the weekend I developed another bout of diverticulitis. Did the usual: fluids, antibiotics, rest, avoided going to the ER, cancelled travel plans.

One of my doctors asked a very simple question: is this happening more frequently? The answer, we both knew, was yes. But I don’t have a Personal Health Record (PHR) that in principle, through a few clicks, would give a time-frame graph of the bouts and severity of the episodes over the past several years.

The last time this happened, and the time before that, I thought I’d finally start a PHR. Like most compulsive patients, I keep records about my health. In the folder in my closet in a cheap old-fashioned filing box, the kind with a handled top that flips open, I’ve got an EKG from 15 years ago, an OR report from my spine surgery, copies of lab results that the ordering physicians chose to send me, path reports from my breasts, a skin lesion or two, and, more recently a colonic polyp, bone density studies from 2004, EMGs and more, essentially miscellaneous results.

None of the records I have are digital.

A few years back I considered using Google Health. But their service, as I understood it, involved scanning documents and uploading them to the Cloud, or paying someone else to do so. That sounded like a hassle. But even had I done that, I wouldn’t have been able to, say, see a graph of my hemoglobin since 1986, or something as simple as my weight changes over time. When Google Health folded a few months back, I was disappointed. At the same time, I breathed a sigh of relief that I hadn’t invested my personal and limited energies into putting my records there.

But now what?

I searched for a PHR, again on-line, and found some commercial stuff, mainly targeting doctors’ offices and larger health care systems. Medicare’s information on Managing Your Health Information Online offers bullet-point explanations on Why Use PHRs?

But I needed no convincing. What I need is software, or a platform, that’s user-friendly and secure. Ideally mine would mesh with my physicians’ records, but my doctors use a variety of record systems. So it’s up to me to integrate the data, if anyone will. The problem is there’s little out there, as best I can tell, that’s intended for patients. Most IT companies are, for now, focused on getting doctors to sign on.

So I’ll start an Excel spreadsheet, today, on my PC. There must be a better way.

Related Posts:

Final Word on Avastin, and Why We Need Better Physicians

Today’s breaking breast cancer news is on Avastin. The FDA has just announced, formally, that it will rescind approval for the drug’s use in people with metastatic breast cancer. Commissioner Dr. Margaret Hamburg writes this her statement:

I know I speak on behalf of the many physicians that have been involved with this issue here at the Food and Drug Administration and elsewhere in saying that we encourage patients, and those who support them, to ask hard questions and demand explanations concerning the drugs that are recommended to treat serious illnesses.

On this much I agree with Dr. Hamburg – that patients and others, including doctors who prescribe treatments to patients with likely incurable illnesses, and all medical conditions, for that matter, should ask hard questions.

Others have already, immediately expressed that the FDA did the right thing. Because they think the FDA’s decision was rational, and it was. Likely there’ll be an editorial in the paper I usually read, celebrating the victory of reason over anecdote. The WSJ, whose words tend to align more with business interests, will likely be critical. Opponents of health care reform will, inappropriately and mistakenly, use this as an example of rationing, which it isn’t.

The fact is that many, and possibly most, medical treatments are given in the absence of studies to justify their use. So you might ask, instead, why give chemotherapy to most stage IV cancer patients. Or why give it in the adjuvant setting? Apart from some tumors, like some kinds of lymphoma and leukemia, and common breast and testicular cancers, and a few others, when carefully measured the benefit is often slim.

What I think is that Avastin is a scapegoat of sorts, a costly drug not particularly worse than many others, nor better, and that helps a small minority of women with a lethal disease for reasons their doctors can’t predict or explain.

We experiment, on insurance and Medicare dollars, with so many costly treatments. Bone marrow transplants, at a cost of hundreds of thousands of dollars per patient, for example, are given to some with little formal proof of benefit for the approved indications. But there’s a lobby for these treatments. Support comes from hospitals profiting from transplant procedures and, more subtly, from academic physicians who’ve built careers in that field and write papers about their benefits, complications and management. I might cite other complex, costly and unproved examples in oncology, surgery and other fields of medicine, but that’s not the real point for today.

What I wonder is, ironically, because the data on Avastin were collected so carefully, that its lack of effectiveness over a population of women was better-documented than has been the lack of evidence for other drugs and regimens. Besides, there’s no group of hospitals and doctors whose profit and livelihood, respectively, depends on giving Avastin to just a few people with metastatic breast cancer. There was just Genentech, an easy big-Pharma target, and a few women, pleading for continued access to a drug that’s helped to keep them alive.

(I wonder, also, had those patients who testified been men, would their words have been taken more seriously?)

Meanwhile, doctors can keep giving Avastin to patients with other forms of cancer, for which its efficacy is not so different as you might think. Like any drug, this drug’s response varies from patient to patient for every tumor type that it might be given. And the physicians can still give Avastin, as the commissioner points out in her decision, to women who can pay for it, by circumstances of their particular insurance, or good fortune of wealth. But some of these women’s families will be hurt hard by this FDA decision. Most are in the 99%.

And so maybe what we really need are better doctors, not only in oncology, who would carefully monitor patients when they give any and every medical treatment and stop it if it’s not working, and continue only if it helps, and would communicate and obtain informed consent through meaningful discourse.

If we had that, we’d save a lot of money, and get better care.

Related Posts:

Thoughts, on Getting My Photo Taken at a Medical Appointment

A funny thing happened at my doctor’s appointment on Friday. I checked in, and after confirming that my address and insurance hadn’t changed since last year, waited for approximately 10 minutes. A worker of some sort, likely a med-tech, called me to “take my vitals.”

She took my blood pressure with a cuff that made my germ-phobic self run for self-regulation, i.e. I stayed quiet and didn’t express my concern about the fact that it looked like it hadn’t been washed in years. I value this doctor among others in my care, and I didn’t want to complain about anything. Then the woman took my weight. And then she asked if she could take my picture, “for the hospital record.”

I couldn’t contain my wondering self. “What is the purpose of the picture?” I asked.

“It’s for the record,” she explained. “For security.”

I thought about it. My picture is pretty much public domain at this point in my life, a decision I made upon deciding not to blog anonymously. Besides, most everyone at the medical center used to know me, including the receptionists, janitors, cafeteria cashiers, nurses’ aides, social workers, deans, full professors, geneticists, fellows in surgery and old-time voluntary physicians, among others who work there. So why didn’t I want this unidentified woman who works in my oncologist’s office to take my picture?

It made me uncomfortable, and here’s the reason: My picture is a reminder that, without it, I might be like any other patient in the system. They (administrators?, nurses, other docs, maybe even my future doctors) will need or want the picture to recall and be certain who Elaine Schattner is.

Don’t get me wrong. I agreed to the photo after all of maybe 20 seconds deliberating. (And my doctor was, I soon learned, duly informed I’d “had an issue” with it. Was that for just asking the reason?) The unidentified med-tech person used an oddly small, ordinary pink camera to complete her task.

When I met with my doctor, she explained that the photo is for security and, essentially, to reduce the likelihood of errors. The hospital has records of so many thousands of patients, many who have similar or identical names. There are good reasons to make sure that your notes on “Sally Smith” are entered into the chart of “Sally Smith” who is your patient.

It’s understandable. I remember when at the nurses’ station there’d be a sign (on “our” side) saying something like “CAREFUL: Anna Gonzalez in 202, Alma Gonzalez in 204b,” or something like that.

Patients blur.

It’s hard, veritably impossible, for most doctors and nurses to keep mental track of all of the patients they’ve ever seen and examined. There’s utility in the new system. Yes, it’s a good idea for a doctor, say upon receiving a call from a woman she hasn’t seen in 3 or 6 or 9 years, to see her picture in the chart, as a reminder.

But I hope my doctors know who I am, and not just what I look like in the image.

Related Posts:

HCR Law Requires Insurers to Cover Routine Care for Patients Participating in Clinical Trials

Something I learned at the MBCN conference is that the Patient Protection and Affordable Care Act of 2010 (PPACA, a.k.a. HCR), will require that private insurance companies cover the routine costs of medical care for patients participating in approved clinical trials.

Medicare does so already, said Dr. Tatiana Prowell, an oncologist on the Johns Hopkins faculty who spoke at the meeting. Indeed, it says so on a CMS document.

The Association of Community Cancer Centers provides a readable section on the relevant changes, including definitions of “routine costs” and what are “approved trials” according to the new law.

All for now –

Related Posts:

Note to Government: Please Don’t Pull Back on Patient Safety Regulations

A few days ago I had a colonoscopy to evaluate some gastrointestinal problems. Subjective summary: Yuck. Downing 3 liters of Nu-Litely, a hyper-osmotic colonic cocktail prep, does not make for a pleasant Sunday afternoon, evening or night. As for the procedure itself, I don’t know how Katie Couric did it on TV.

But what made the procedure tolerable, and non-scary, and worthwhile, was that it was done by a careful, experienced gastroenterologist in a well-run facility. The outpatient unit where I had my colonoscopy employs reputable anesthesiologists and maintains functional, appropriate monitoring instruments and, should they be needed, life-saving equipment.

Why I mention this recent ickiness is this –

This morning’s paper reports that the U.S. administration plans cuts in hospital regulations:

… after concluding that the standards were obsolete or overly burdensome to the industry.

Kathleen Sebelius, the secretary of health and human services, said the proposed changes, which would apply to more than 6,000 hospitals, would save providers nearly $1.1 billion a year without creating any “consequential risks for patients.”

A few aspects of the proposed regulatory pull-back seem reasonable, like allowing hospitals to delegate more work to nurse-practitioners. But some of this regulatory reversal sounds dangerous:

…Other proposals would eliminate requirements for hospitals to keep detailed logs of infection control problems…

…Federal officials would also eliminate a detailed list of emergency equipment that must be available in the operating rooms of outpatient surgery centers. Such clinics would have leeway to decide what equipment was needed for the procedures they performed.

Fortunately, the administration is accepting public comments on this matter for 60 days. But they could make it easier. Instructions from the HHS press release involve a series of links:

To view the proposed and final rules, please visit: www.ofr.gov/inspection.aspx…Both proposals invite the public, including doctors, hospitals, patient advocates, and other stakeholders, to comment.  To submit a comment, visit www.regulations.gov, enter the ID number CMS-9070-P or CMS-3244-P, and click on “Submit a Comment.”

My position is that any lessening of infection control is a disservice to patients. As for monitoring of outpatient facilities where procedures are performed, it’s crucial; patients rely on maintenance of modern, clean and functional equipment in places where they receive medical care.

My bottom line: Patient safety should take precedence over cost-saving measures by the inspectors and the inspected.

Related Posts:

The Immeasurable Value of Continuity of Care

Today I visited my internist for a checkup and flu shot. We talked about how I’m doing, and she examined me, and we discussed what procedures I ought have done and not done. She’s been my doctor since the summer of 1987, when I was an intern at the hospital.

We reviewed so much that has happened in the interim.

How rare it is, now, to have a doctor who knows me. Continuity in care is so valuable.

One of my greatest fears is being in the hospital again, and having hospitalists – doctors who work full-time in the hospital – be the ones to see me each day, and make decisions about what I need. Yet I’m bracing for it because, well, that’s how it is, now.

From a health care administration perspective, I recognize the value of delegating inpatient care to physicians who are not my usual doctors. And from the perspective of a physician who after hours and on weekends, would walk to and from the hospital, back and forth, countless times, to see my patients when they were sick, I know it’s neither cost-effective nor wise for physicians to push themselves to get over to the hospital before or after they’ve gone home, and called everyone back, and maybe eaten dinner. Doctors need rest, too.

But as a patient, when I’ve been in the hospital, nothing was more reassuring than visits by my usual doctors – my internist, my oncologist, my surgeon, my orthopedist…Being cared for by strangers, however competent, is not the same, although there may never be a study to prove it.

Related Posts:

Reducing Cancer Care Costs by Comparative and Cost-Effectiveness Research (CER)

Well, it’s the day after Labor Day, time to resume our discussion of Bending the Cost Curve in Cancer Care.

We’ve reached the end of the list, on ideas to reduce oncology costs put forth by Drs. Smith and Hillner in the May 25 issue of the NEJM. Really this 10th and final point intended for oncologists is two-in-one: “The need for cost-effectiveness analysis and for some limits of care must be accepted,” they chart. So doctors should embrace studies of comparative effectiveness and cost effectiveness.

Hard to argue with reason – they’re correct, of course. They write:

… The national imperative is to empower a transparent, acceptable, equitable, politically independent agency for guidance in making tough choices in the public interest so that doctors do not have to make them at the bedside.60 Ultimately, we will have to make decisions based on some criteria, and comparative-effectiveness61 and cost-effectiveness62 analyses are good ways to align resource use with the greatest health benefit.

This sounds great, and is probably right, but I don’t think it’s realistic.

A more detailed consideration on the issue of cost-effectiveness, IMO, came out a few weeks later, also in NEJM: Comparative Effectiveness Research and Patients with Multiple Chronic Conditions. This piece, by Drs. Mary Tinetti and Stephanie Studenski, considers the problematic application of CER in the real world.

The problem with CER, these authors emphasize, is that most medical patients have more than one condition and many are elderly; clinical trials tend to include, exclusively, patients who don’t have more than one major illness are relatively young. This limits the physicians’ abilities to apply data to their patients.

What’s more, reported results tend to focus on central results, but most patients fall elsewhere on measured curves:

The heterogeneity of treatment effects will further complicate CER. Although studies typically report average effects, most participants experience more or less benefit and harm than average. Such heterogeneity results from variability in patients’ initial level of risk for a given outcome, in their responsiveness to treatment, and in their vulnerability to adverse effects — issues with particular relevance to patients receiving treatment for multiple coexisting conditions.

The authors, who recognize the need for better research to support treatment decisions, write that “CER will probably accelerate the movement toward outcome-driven decision making, reimbursement, and quality assessment. As this shift occurs, we must move toward a focus on cross-disease, “universal” outcomes in research and clinical care.” Their thesis gets more abstract (which I admire), but meets a wall or two: the lack of consensus on a set of universal health outcomes, different parameters measured by the likes of the VA administration, CMS, the FDA, NIH and other huge agencies.

They make a practical suggestion, about the need for head-to-head comparisons in CER:

… interventions such as exercise that affect multiple conditions simultaneously should be a high priority…Studies should include assessment of the burden of treatments for patients and families. Another CER priority should be the examination of treatments for common pairs of diseases in which treatment of one may exacerbate the other. For example, when hypertension and osteoporosis coexist, what treatment best minimizes the risk of adverse cardiovascular outcomes without increasing the risk of falls and fractures?

All of this sounds reasonable to this patient-doctor, but it’ll take a lot of time and money to accomplish effective CER that encompasses the needs and conditions of sufficient numbers of patients in disease and age combinations to power any meaningful studies. You have to wonder at some point, as I have been lately, is all this clinical research worth the effort?

That said, I respect this paper‘s conclusions on CER:

Researchers have largely shied away from the complexity of multiple chronic conditions — avoidance that results in expensive, potentially harmful care of unclear benefit. We cannot improve health care’s quality, effectiveness, and efficiency without addressing its greatest consumers. Development and testing of innovative approaches to care for patients with multiple chronic conditions could prove the most lasting legacy…

My bottom line: CER, and consideration of treatment costs, should underlie reduction of cancer care costs in the near and long-term future. As to how we accomplish sufficiently careful research, and avoid inappropriate cutting of helpful treatments – especially those that prove beneficial for some younger and otherwise healthy cancer patients – is one of the two main challenges ahead.

(The other big challenge, mainly a moral one, is the subject of rationing, to which Smith and Hillner allude but don’t detail, and which subject I won’t address in this post.)

Meanwhile: thorough, apolitical, nuanced and transparent reporting of trial results would help doctors, patients and the general public understand what information is available.

Finally, in the next month or so I will look back over the full, provocative and generally excellent list by Drs. Smith and Hillner, and see what holds hope for the future of cancer medicine. What’s clear is that the path ahead mandates clear thinking through some very tough clinical decisions.

Related Posts:

newsletter software