Category: Uncategorized

Looking Back at the RWJF Challenges

Nov 9, 2018

Last Month in Oncology with Dr. Bishal Gyawali

Nov 8, 2018• 8

By BISHAL GYAWALI MD

Me-too deja vu

I read the report of a phase 3 RCT of a “new” breast cancer drug but I had the feeling that I had already read this before. Later I realized that this was indeed a new trial of a new drug, but that I had read a very similar report of a very similar drug with very similar results and conclusions. This new drug is a PARP inhibitor called talazoparib and the deja vu was related to another PARP inhibitor drug called olaparib tested in the same patient population of advanced breast cancer patients with a BRCA mutation. The control arms were the same: physician choice of drug, except that physicians couldn’t choose the one drug that is probably most effective in this patient population (carboplatin). The results were nearly the same: these drugs improved progression-free survival, but didn’t improve overall survival. In another commentary, I had raised some questions on the choice of control arm, endpoint and quality of data about the olaparib trial when it was published last year. This current talazoparib trial is so similar to the olaparib trial that you can literally replace the word “olaparib” with “talazoparib” in that commentary and all statements will stay valid.

The oncology version of half-full, half-empty glass

The PARP inhibitors olaparib and niraparib are also approved in ovarian cancer based on improvement in progression-free survival (PFS), without improving overall survival (OS). If a drug doesn’t improve OS but improves only PFS, it should also improve quality of life to justify its use. According to two new reports, these drugs do not appear to improve quality of life. The niraparib trial reported that the patients were able to “maintain” their quality of life during treatment while the olaparib trial reported that olaparib did not have a “significant detrimental effect” on quality of life. I find it remarkable that a drug that isn’t proven to improve survival is lauded for not significantly worsening quality of life … at $10,000 a month!

It is also important to recognize that these drugs were tested as maintenance therapy against placebos. For “maintenance therapies,” as explained in this paper, improving PFS alone is not an important endpoint. That’s why I am also not excited about this new trial of sorafenib maintenance in ovarian cancer. A drug has to be very ineffective to fail to improve even PFS as a maintenance therapy against placebo.
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Health in 2 Point 00 Episode 57

Nov 7, 2018

On Episode 57 of Health in 2 Point 00, Jess and I report from Exponential Medicine. In this episode, Jess and I talk about digital surgery and how Shafi Ahmed and Stefano Bini are transforming surgical training. She also asks me about my favorite session, one by Anita Ravi on health care for those who have been sex trafficked. Other highlights include ePatient Dave’s talk about access to data for patients and letting patients help, and Leerom Segal’s overview of why voice matters- Matthew Holt

The IPCC Confirms Life As We Know It Will Soon Cease to Exist

Nov 6, 2018• 7

By DAVID INTROCASO PhD

THCB readers may recall last year in early June when the Trump administration announced it would withdraw from the 2015 Paris climate accord and earlier this January when the World Economic Forum met to discuss its global risk report that included the chapter, “Our Planet on the Brink,” I discussed in part (here and here) the health care industry’s indifference to global warming (See also my related 3 Quarks Daily essay.) Now comes the United Nation’s Intergovernmental Panel on Climate and Change’s (IPCC’s ) latest report. Once again overwhelming scientific evidence that confirms life as we know it on this planet will soon cease to exist is received with apathetic insouciance.

Created in 1988 the IPCC is considered the world’s definitive scientific body on climate change and co-winner with Al Gore of the 2007 Nobel Peace Prize, finalized in early October its report, “Global Warming of 1.5°C.” The 2015 Paris accord called for the report. It was prepared by nearly one hundred scientists who analyzed thousands of the most recent scientific evidence. The report’s summary was accepted by over 180 countries including the American and Saudi Arabia delegation during the IPCC’s meeting recently concluded in South Korea.

What is newsworthy about the IPCC report is its conclusion that keeping or holding temperature increases below 2°C, the goal of the Paris agreement, would not avoid the catastrophic effects of global warming. At 1.5°C life on this planet would suffer serious or dire harm, at 2°C catastrophic harm. Specifically, the report compared the impact between a 1.5°C (2.7°F) increase in temperature with a 2°C (3.6°F) increase (The earth has already warmed by 1°C since the pre-industrial era). Among numerous other findings, should temperatures increase to 1.5°C, the report found of 105,000 species studied, four percent of vertebrates (that include us), eight percent of plants and six percent of insects would lose half of their climatically-determined geographic range. At 2°C, the percents double to triple. Global crop yields will decline significantly. At 1.5°C we will lose 70 to 90 percent of coral reefs, at 2°C there will be a 99 percent loss. At 1.5°C Marine fishery losses or the global annual catch loss would be 1.5 million tons, at 2°C they double.

2018 Midterms: The Year of the Female Physician

Nov 5, 2018• 9

By NIRAN AL-AGBA MD

While women make up more than half of the U.S. population, an imbalance remains between who we are as a nation and who represents us in Congress. The gender disparity is no different for physicians: more than one third of doctors in the U.S. are women, yet 100 percent of physicians in Congress are men. To date, there have only been two female physicians elected to Congress.

However, in the coming midterm election, there are six races with a chance at making history. It’s these battles which could make 2018 “The Year of the Female Physician.”

I remember being a first-time voter in 1992, labeled at the time “The Year of the Woman.” I was a sophomore at Michigan State University and turned 18 just three days before the election. Following the contentious Supreme Court hearings involving Clarence Thomas and Anita Hill, an unprecedented number of female candidates were vying for office that election year.

President George H. W. Bush was vilified for an appalling answer to the question of when his party might nominate a woman for President. “This is supposed to be the year of the women in the Senate,” he quipped. “Let’s see how they do. I hope a lot of them lose.” Frustrated about the state of gender inequality in politics, a little-known “mom in tennis shoes,” Patty Murray, decided to run for the U.S. Senate to represent Washington. She won, paving the way for an unprecedented number of women to enter national politics over the next 30 years. Still, very few of them have come with a background in medicine.

Health in 2 Point 00 Episode 56

Nov 2, 2018• 1

On Episode 56 of Health in 2 Point 00, Jess and I report from Livongo’s new office in San Francisco. In this episode, Jess asks me about Carrot Health’s $25 million raise for their digital smoking cessation program and 98point6’s $50 million raise for their on-demand primary care app. We also have our special guest star Dr. Jennifer Schneider here to tell us about how Livongo is working to Silence Noisy Healthcare with Applied Health Signals- Matthew Holt

The Road Not Taken: The Unrecognized Harm of Excessive Regulation

Nov 1, 2018

By David Shaywitz

The difficulty of creating new and better medicines has been the subject of extensive – at times excessive – soul searching, a process that’s intensified as high-profile patents expire, along with their associated revenue streams, traditionally relied upon to support future R&D. As a result, both biopharma companies and patients awaiting new treatments find themselves struggling for viable solutions.

Predictably, industry (where I obviously reside) attributes excessive regulation, regulators say “don’t blame us,” and considered reporters and observers typically try to split the difference – maybe everyone is a little bit at fault.

The problem with this resolution is that it’s a cop-out; while there is clearly a measure of shared responsibility, it’s willful blindness not to recognize the extent to which a deliberate and very conscious regulatory policy is putting a damper on what has traditionally been the world’s most vibrant drug development ecosystem.

It’s not that other factors (such as the complexity of science) aren’t important – in fact, it’s precisely because developing new drugs is challenging, so inherently difficult, that’s it’s crucial to do everything within our control to work together and create an environment, an ecosystem, that stimulates and enables meaningful innovation.

The most significant – and potentially, most correctable (which is why it’s especially frustrating – it’s explicitly of our own making) problem – is that regulators, as others have astutely observed, seem to have misapplied the “precautionary principle,” colloquially understood as “first, do no harm.” The problem isn’t so much the sentiment as the way it’s reduced to practice.

The Rule of Thirds

Nov 1, 2018

By Marya Zilberberg, MD

When I was a medical student, I did a lot of rotations at the Boston VA in JP. I loved my patients there — they were patient and kind and stoic. One of the best rotations I did was Hematology, where Lou Fiore was my preceptor. Lou was not only an excellent teacher, but also a terrific doctor and a good human being all around. He used to start our days together by saying, “I’m gonna teach you one thing today.” And teach us he did, at least one thing per day. Now I teach. And on occasion I have used the Lou Fiore “I’m gonna teach you one thing today” promise. Well, today is one of those days: I’m gonna teach you one thing.

And here is that thing. I am sure I am not the first one to notice this, but I still think of it as the “Zilberberg rule of thirds.” The gist of it is that, for clinical research purposes, one can think of patient populations crudely in thirds: there is one third who are too sick to benefit from any of our interventions, there is one third who are too healthy, so that no matter how we try to tweak, their outcomes will not change, and the middle third, which comprises the “sweet spot” for intervention. So it is a fool’s errand to pursue proof of concept studies in either of the bracketing thirds, since it is only the middle third that is likely to show a signal.

Pharmaceutical manufacturers do not always appreciate this trichotomy. Look at Vioxx, for example: when used in patients who were essentially healthy, an unacceptable safety signal arose that drove the drug off the market. Same for SSRIs, where the ill-conceived enthusiasm for treating marginal depression cases seems to be debunking the entire serotonin hypothesis. The flip side is sepsis research: septic shock patients are so far gone that it is difficult for any single therapy to alter their outcomes. Just look at the Xigris story, as well as myriad other therapies that tried and failed. This is the rule of thirds at its most pronounced.

In HEOR the rule of thirds holds as well. To prove cost effectiveness the following questions need to be asked:

1. Is the disease in question prevalent?

2. Is the economic impact of the disease known and substantial?

3. Does the diagnostic/therapy in question alter the course of the disease in such a way as to be significant?

If the answer to any of the questions above is “no,” you really need to think carefully about the value proposition.

Some of you will bring up the inter-individual differences, the heterogeneous treatment effect, etc. And yes, these are supremely important. However, though the framework I propose here is simplistic, we have to start somewhere. To be sure, there is a more nuanced approach to this beast, but generally, one will not go wrong by asking these questions before committing huge resources to a project, particularly if the answer to question 2 or 3 is a resounding “no.” So, even in health economics it behooves one to know the Zilberberg rule of thirds: choose the right population where the diagnostic/therapeutic advance and its costs can be justified by a substantial gain in the outcomes.

And that is your one thing for today.

Marya Zilberberg, MD, MPH, is a physician health services researcher with a specific interest in healthcare-associated complications and a broad interest in the state of our healthcare system. She is the Founder and President of EviMed Research Group, LLC, a consultancy specializing in epidemiology, health services and outcomes research. She is also a professor of Epidemiology at the University of Massachusetts, Amherst. Dr. Zilberberg blogs at Healthcare, etc.

Racing to Nowhere

Nov 1, 2018

By Merrill Goozner

I had dinner over the weekend with a close friend who is a breast cancer survivor (her word) and a former avid participant in the annual marathons sponsored by the Susan B. Komen Foundation. Her status as a former activist was new. “Is this what we were racing for?” she said. She is skeptical by nature, and the brouhaha over Komen’s back-and-forth over funding Planned Parenthood last week didn’t make her angry. It merely flipped the switch that changes skepticism into cynicism. To paraphrase the old Phil Ochs song, she ain’t a marchin’ anymore.

I try to avoid bringing my knowledge about medical issues into private discussions (I’m not a doctor, and I take that caveat seriously. But as readers of this blog know, I’ve written extensively about recent controversies in breast cancer research, including the dust-ups over the U.S. Preventive Services Task Force recommendation that women under 50 can eschew mammography, and the Food and Drug Administration’s decision to withdraw Avastin’s approval for breast cancer). Yet my friend asked me pointedly about what I thought about Komen and why they did what they did. She knew nothing about the organization she had been supporting for many years, and now wanted answers.

Biopharma + Digital Health?

Nov 1, 2018

By David Shaywitz

Biopharma – especially big pharma – gets all sorts of grief for being large, stodgy, and unable to innovate (or evolve);this Corey Goodman interview represents the perspective well.

Before writing off these companies entirely, however (an ignorant reaction in any case), it’s important to consider how much experience they have in doing two very difficult, very important things: (a) documenting the medical value of their products through a rigorous series of clinical studies conducted in a highly regulated environment; and (b) navigating their way through a complex maze of stakeholders in order to successfully market their products.

Much of the difficulties facing the industry these days stem not from their lack of regulatory experience or marketing skill, but rather from the intrinsic value proposition of the products they offer; simply put, making an impactful new drug is extremely hard and quite expensive, as Matt Herper’s recent piece makes clear.

My sense is that the view from the digital health/start-up side is in many ways the mirror-image of this: the space seems to be brimming with promising nascent ideas; yet, as I’ve discussed before, the measurable health impact of these technologies is usually unclear (at best).

Some emerging digital health companies don’t worry about this – they are deliberately seeking to circumvent the regulatory process by aiming directly at consumers, and avoiding explicit health claims. Others seem to be leaning pretty heavily on the concept of being so disruptive that, in effect, the world will change for them.

I’d suggest that there still is a huge opportunity for digital companies that are keen to robustly demonstrate health benefits, at the high level of rigor that is standard in the medical products industry.Continue reading…