When Oncologists Look at Oncology, They See the Same Dire Shortages Year After Year

Survey Research at the Clinical Frontlines

In August and November 2011, we wrote here about the increase in oncology drug shortages and the implications for oncology patient care.  We’d been moved by alarming media reports, including a New York Times Op-ed by Ezekiel J. Emanuel, MD, PhD, to poll oncologists about their personal experiences in the January 2012 wave of our ongoing survey initiative, “Oncologists Look At Oncology". 

Nearly all of the 204 oncologists (95%) who participated in our 2012 survey had seen patients in the prior year (2011) who were unable to receive timely treatment due to drug shortages, with half (49%) encountering this problem on at least a monthly basis throughout the year.  A full 85% said they’d had patients who were unable to receive the best therapy at all because of drug shortages.  Those data were taken to Capitol Hill by the Community Oncology Alliance as part of a broader conversation that involved Congress and FDA.  Some constructive solutions were proposed by health advocates and policy-makers while essentially nothing happened.  We have become a society that is extraordinarily patient with the unacceptable. 

Cue 2013, and another round of surveys.

This past week, the American Society of Clinical Oncology held its annual meeting in Chicago.  At that meeting, Dr. Emanuel and Dr. Keerthi Gogineni reported the results of a new survey of oncologists which they and their colleagues at the University of Pennsylvania conducted in Fall/Winter of 2012-13. Sadly, they continued to find that 92% of oncologists say that their patients’ treatment has been affected by shortages and 83% have been unable at times to prescribe standard chemotherapy. 

The Deplorable ‘New Normal’ Requires New Guidelines

Oncologists feel that they lack formal guidance about how to make allocation decisions and, therefore, that they must improvise their responses when drugs are unavailable.  Oncologists have substituted scarce generic medications such as leucovorin with more expensive branded options, but the implications of swapping drugs involve far more than reduced cost-effectiveness.  They can lead to reduced efficacy and increased morbidity.

In an interview with CBS Radio, Dr. Gogineni commented that, “These are substitutions for which we sometimes don’t have data about how that affects the outcome for a patient.”  She went on to suggest that guidelines are needed to inform and standardize the decisions oncologists make in times of scarcity.

And indeed, a disheartening number of oncologists polled in our 2012 survey were already convinced that patient outcomes have already been affected by shortages.  Almost half (48%) believed they had had patients whose tumors had recurred because of drug shortages and 40% had at least one patient whom they believe had died sooner. Opinion surveys of oncologists cannot and should not carry the weight of well-designed empirical assessment of patient outcomes, but oncologists are the first to see that these shortages have consequences, and we ignore the early warnings at patients’ peril.    

Safeguarding Legacy Drugs While We Still Need Them

Oncologists have always prided themselves on practicing evidence-based medicine long before “evidence-based” had become a medical mantra.  We should be indignant that patients are now forced to be treated with something other than the evidence-based standard of care simply because we have not found a way to ensure the availability of the best medicines.  And we should despair to think that things have gone so far that there is now a call for new guidelines to compensate for loss of old but important drugs.  Our emphasis on medical discovery should remain absolute and unqualified. But there is grim irony in the implication that forward progress toward newer, more expensive therapies continues to have as an unintended consequence the loss of cheaper therapies we already know to be critically important.

Celiac Disease and Gluten Allergies: Separating the Wheat-related Illness from the Fad

The Fashionable Demonology of Gluten…

A recent article in The New York Times on “gluten allergies” – as distinct from Celiac Disease – is an interesting reminder of the way health-fashionistas can propel a powerful food fad by driving a bandwagon fueled by scant data. Just a decade ago, few people had heard the word “celiac,” and only bakers talked about gluten. Today, many shun gluten in pursuit of vague, putative health improvements, inspired by celebrities and diet missionaries who set fashion trends of all types. People are forever looking to find, and rout, the single dietary culprit that stands between them and general well-being. (If only one could so easily pinpoint the chief obstacle to health, happiness and a submissive GI tract!)

…And the Indisputable Gravity of Celiac Disease

Real or not, widespread claims of gluten allergy can look, to the unsympathetic eye, a little like Munchausen Syndrome. I would have viewed those claims as just a curious cultural trend, were it not for my professional interest in the “real deal” – Celiac Disease, informally known as celiac sprue. Celiac Disease (CeD) is an auto-immune response to gluten: at once insidious and debilitatingly symptomatic, persistent and shape-shifting, life-altering and potentially lethal. It often eludes diagnosis for years due to the astonishing variety of symptoms, from hallmark GI side effects (not always present) to diffuse neurological symptoms; from malnutrition, anemia, and osteoporosis to infertility and miscarriage. Longer-term effects include T-cell lymphoma, the sort of cancer that can spring from chronic immunologic insult. Epidemiological estimates place incidence at roughly 1%, but the condition remains significantly underdiagnosed, even though documented incidence has been rising steadily with the availability of tTG antibody testing, approved in the US a decade ago.

Emerging from the Shadows…

CeD is certainly not a new disease but the medical community has been largely disengaged because the only management is “a gluten-free diet” (GDF), which means there is little to be accomplished through systematic follow-up. Diseases amenable only to lifestyle modification put patients squarely at the controls. And because CeD patients are often highly symptomatic, they also tend to be highly motivated. Many are remarkably knowledgeable and self-directed, often more expert than their physicians. Pioneering celiac crusaders and disease advocacy groups [NFCA, CDF, and CSA] have helped make the world safer for these patients – medically and psychologically – by creating public awareness, increasing access to information, spurring diagnosis, and legitimizing what was for so long a very lonely, neglected affliction. There are some excellent CeD centers around the country but, by and large, physicians in the community are just catching up.

…and Now Catching the Eye of Pharma

Fortunately, the pharmaceutical industry has also begun to pay serious attention. A Baltimore-based company called Alba Therapeutics is partnering with Teva to develop larazotide acetate, an oral peptide that regulates tight junctions and modulates cellular permeability, reducing gluten leakage into the gut.

Alba is currently enrolling patients in its Phase IIb trial at 74 sites around the country. Larazotide acetate is not an immune-modulator; successful trials would position it as an adjunct to diet, significantly enhancing symptom control and, by implication, reducing long-term risk. These patients need an additional backstop because gluten lurks everywhere and, as we know so well from diabetes and other lifestyle-mediated diseases, self-control is a famously imperfect health strategy. Even most of the disciplined patients continue to be symptomatic.

Let’s Not Blur the Picture

This brings us back to the starting point – the probability that many people now on gluten-free diets have nothing at all wrong with them that gluten abstinence can cure, although some are CeD family members who adopt gluten-free diets in an act of solidarity. (The disease is genetic, so people with close family members who’ve received a diagnosis should be screened, even if they are not symptomatic.) Gluten sensitivity remains speculative, despite a tidbit of clinical data and some anecdotal testimony by health professionals. The question is: Does all the attention paid to this pop-culture “wannabe” ultimately help or hinder the process by which CeD, a documented and serious disease, achieves mainstream medical awareness?

One can argue the case both ways. The concept of gluten allergies has put gluten on the dietary map, as well as on most food labels. A flourishing specialized food industry, which has gotten added impetus from the GFD dietary fad, provides CeD patients convenient access to a much larger and tastier array of products. If the fad wanes, the food industry may lose some interest.

On the other hand, we don’t want our received wisdom on gluten and health to come from starlet interviews in Marie Claire. All this misdirection risks blurring the boundaries between “allergies” and true CeD in ways that discourage formal diagnosis and invite casual self-care. CeD patients will always need to be at the helm of their disease -- well-educated and well-motivated to combine serious diet with pharmacology. If ever there was a case for DTC outreach, this is certainly it.

The Annual Physical: Maligned and Misunderstood

In The New York Times' Sunday Review, Elisabeth Rosenthal mounted an attack on the cost-effectiveness of the annual physical, a ritual whose net value has actually been covertly questioned for decades by many health professionals, but whose sanctity has now become safe to challenge in very public view. What we’re seeing today is a seismic collision between two forces: our historic belief that deluxe healthcare, with no test or procedure spared, is an inalienable right, and our urgent need to rethink the value of every entitlement -- including the rituals of care we hold most sacred.

Forget the tricky pharmacoeconomic calculus around PSA tests and mammograms. There’s a larger picture to look at. Problems that require immediate intervention tend to be more acute and symptomatic -- and those emergent problems don’t necessarily present in accordance with the arbitrary timetable by which we set our medical appointments. Annual cycles have astronomical and cultural meaning for us, but the body doesn’t pay them much heed. Even civilians can understand that. And, in fact, the so-called annual physical is a bit of a misnomer anyway. Relatively healthy people and those who are healthcare-averse have check-ups far less often.

Rosenthal’s general perspective is sound but she conflates a few issues to make periodic “well check-ups” seem even less productive, or cost-effective, than they are. Executive physicals are surely capitalism at work, but ironically, the people who seek them out tend to be a very small minority of relatively healthy individuals. And CT scans for headaches or MRIs for lower back pain don’t tend to come about as a result of annual check-ups; they’re usually precipitated by symptoms and sick visits. We may spend way too much on medical tests for symptoms that, on average, are transitory and unimportant, but that problem can be solved by smarter protocols and more disciplined, effective MD-patient interactions. We don’t need to bash the physical to reduce unnecessary testing.

Actually, most of the testing done for annual physicals is relatively inexpensive and non-invasive blood work, and there are useful things to be learned from it, even in patients who feel quite well. The PSA, which can produce false-positives, should be accompanied by a DRE to palpate the prostate so net costs need not be unduly high. And as someone who has helped bring bisphosphonates to market (but doesn’t choose to treat her mild osteopenia with any of them), I count on a DEXA scan every few years to track the success of exercise, provide a platform for discussion about supplements, and give me greater clarity on my risk profile.

Here are some other things the annual physical does:

• It creates a more coherent picture of each patient for his or her primary care physician. If properly spent, time in the annual physical fosters the sort of MD-patient relationship that’s bound to produce more cost-effective healthcare -- for instance, by preventing very expensive ER visits, or by promoting lifestyle change and modifying risk profiles at earlier points.
• It is probably the most reliable way to diagnose and act on hypertension in patients who are otherwise healthy, in a medical culture that has clearly documented the long-term mortality benefits of increasingly tighter BP control.
• It gives physicians and patients a regular forum for discussing trends in BP, cholesterol, and blood glucose -- and for finding trigger points that persuade recalcitrant patients to embrace more aggressive pharmacologic strategies once diet and wishful thinking have truly failed.
• It allows physicians to monitor the side effects associated with all those life-extending therapies they prescribe -- drugs that we all have come to see as involving complex risk-benefit trade-offs requiring more vigilant post-market surveillance.

There are lots of ways to cut medical costs but it’s not clear that the annual physical is necessarily the greatest source of leverage -- or the right sacred cow to slaughter. We need to decide how to use those precious 45 minutes in better ways, perhaps. But we ought to work harder on figuring out how to keep insured patients out of the ER for non-emergencies than keeping them out of the PCP’s office for regular check-ups. Developing improved lines of communication (at the annual physical, perhaps?) will go a long way towards producing healthier patient behaviors, less impetuous use of testing, and more effective patient-clinician collaboration in the realm of both prevention and treatment.

FDA DTC and ROI: The simmering alphabet soup of pharmaceutical consumer outreach

The New FDA: champion of DTC and of survey-guided policy input

Just a few weeks ago, the FDA closed its public comments period on a questionnaire for a survey it intends to conduct later this year among health care professionals. The goal of the survey is to gather insight on how consumer-targeted promotion ultimately impacts the quality of interactions and decisions in provider offices around the country. The instrument itself is still a work in progress, and no one will be surprised to hear that our firm made a number of friendly, civic-minded suggestions. It’s clear that FDA has become a patron of survey research for many purposes -- policy development as well as risk surveillance.

The very fact that this particular survey is on the docket speaks volumes about what many FDA-watchers have already concluded: that the agency has morphed from wary and grudging to comfortable and upbeat about the benefit of allowing pharma to converse with patients. After several decades of experience, the FDA seems ready to conclude that direct-to-consumer advertising (DTC) can do more than bring relevant therapies to broader awareness. It can also, through “fair balance,” arm patients with many of the pros and cons to promote more informed conversation with caregivers. Actually, my husband (an attorney, not a citizen of our pharma community) has often expressed astonishment that any of my clients pay to run ads on TV because he is utterly convinced that they make patients run fast in the other direction. As it happens, he is mistaken.

Fitness versus Health: Marathons Test Not Just Endurance but Logic Too

Safer on the sidelines?

The mortality toll of the 2011 Philadelphia Marathon was two runners out of approximately 25,000, a death rate that proponents of the event might represent as less hazardous than the risk of commuting the distance by car. And probably much safer than couch-bound obesity. Even when we take into account the many people who require first aid for dehydration or suffer orthopedic injuries, the hazards of marathon participation might strike many as relatively low. Life is risky business, after all, and testing human limits -- for pleasure or heroism -- often comes at a price.

Nonetheless, it is curious to observe how sanguine health experts and the public have become about tests of endurance that can result in needless death, and how little discussion we hear in the aftermath about the wisdom or health value of marathon participation. That’s because marathons -- once considered an “extreme sport” for the very few -- are now an icon of our fitness culture, attracting virtual hordes of runners in cities across the country, more and more of whom run the full distance each year.

Marathons are a spectator sport and a badge of fitness honor -- not to mention a source of mood elevation for those addicted to long-distance running. And for the cities that host them, they are also very much a business that creates dollars, press, and caché. When endurance events like marathons and triathlons are promoted by health celebrities and fitness missionaries like CNN’s Sanjay Gupta, they gain more credibility and many more converts.

Oncologists Answer the Question: What is an Added Month of Life Worth?

We recently surveyed U.S. oncologists in order to gain their perspectives on the emerging changes and challenges in the cancer landscape. The survey results spotlight an increasing tension between oncologists’ overwhelming optimism about the state of advancing science and their deep pessimism about the affordability of care.

One particular line of survey questioning addressed oncologists’ views of the value of incremental survival in the context of advanced cancer. We asked a series of questions designed to assess whether oncologists believe a new therapy that improves survival would be “worth it” under a variety of different contextual scenarios. Holding as a constant the assumption that the baseline price of the next best alternative care would total $15,000, we systematically varied: (1) expected survival time with the next best alternative care (either two months or nine months); (2) incremental survival with the new therapy (from one month to 12 months); and (3) the total cost of the new therapy (from $40,000 to $120,000 -- in other words, an increase in $25,000 to $105,000 over the cost of the next best alternative).

There are two key findings from those questions. First, in order for a majority of oncologists to declare the new therapy “worth it” even at the lowest of the prices we tested, the therapy must deliver a median of three additional months of life. Second, for the majority to judge those three additional months of survival an acceptable value, the cost of each additional month must be no more than roughly $9,000 to $10,000, regardless of whether baseline survival is two months or nine months.

A Survey of Battlefields in the War on Cancer: Oncologists Reporting from the Front Lines

In 2008, we launched an oncology market surveillance program, “Oncologists Look at Oncology: Prognosis for U.S. Cancer Care.” We were moved to do this by what we were hearing from oncologists as we conducted in-depth interviews with them on behalf of our clients. Our clients in the field, who range from small startups to leading “Big Pharma” companies, shepherd innovative molecules from the bench to the clinic and, if successful, to the commercial marketplace. But over 35 years after the “War on Cancer” was famously declared by President Nixon in 1971, what we were hearing from oncologists on the front lines of cancer care was a sense of frustration, even despair.

A significant part of oncologists’ frustration at the time was financial. In 2006, Medicare and Medicaid reimbursement to physicians for in-office intravenous cancer medications was cut dramatically. Private practice oncologists had been earning 50 percent or more of their total personal income from profits on IV medication -- profits earned directly from reimbursement paid by public and private payers. The industry published fictional “average wholesale prices” (AWP) that set the reimbursement physicians would receive, but physicians were able to purchase drugs at prices substantially below AWP. Centers for Medicare and Medicaid Services’ updated reimbursement policy based on actual average selling prices rationalized reimbursement but changed the game for oncologists.

But loss of personal income wasn’t the only thing that seemed to have disheartened oncologists. They told us that they were sending more patients to hospitals for drug administration when coverage was uncertain -- even though patients generally feel more comfortable receiving treatment in familiar, less institutional treatment settings -- because private practices could no longer absorb unreimbursed drug costs. They told us that they were unable to treat patients with the best available care because of patients’ inability to afford requisite out-of-pocket co-payments. They told us that they did not see how providers or patients or payers could keep pace with the escalating costs of new cancer therapies. They told us that their colleagues were retiring and their children were pursuing specialties other than oncology because both financial compensation and lifestyle were better in procedure-oriented fields.