Categories

Category: Pharmaceuticals

AI Doesn’t Ask Why — But Physicians And Drug Developers Want To Know

By DAVID SHAYWITZ MD

At long last, we seem to be on the threshold of departing the earliest phases of AI, defined by the always tedious “will AI replace doctors/drug developers/occupation X?” discussion, and are poised to enter the more considered conversation of “Where will AI be useful?” and “What are the key barriers to implementation?”

As I’ve watched this evolution in both drug discovery and medicine, I’ve come to appreciate that in addition to the many technical barriers often considered, there’s a critical conceptual barrier as well – the threat some AI-based approaches can pose to our “explanatory models” (a construct developed by physician-anthropologist Arthur Kleinman, and nicely explained by Dr. Namratha Kandula here): our need to ground so much of our thinking in models that mechanistically connect tangible observation and outcome. In contrast, AI relates often imperceptible observations to outcome in a fashion that’s unapologetically oblivious to mechanism, which challenges physicians and drug developers by explicitly severing utility from foundational scientific understanding.

Continue reading…

Last Month in Oncology with Dr. Bishal Gyawali

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 niraparibtrial 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.
Continue reading…

Part 2: Bypassing Prior Authorizations

By NIRAN AL-AGBA, MD

A few weeks ago, I saw a young patient who was suffering from an ear infection. It was his fourth visit in eight weeks, as the infection had proven resistant to an escalating series of antibiotics prescribed so far. It was time to bring out a heavier hitter. I prescribed Ciprofloxacin, an antibiotic rarely used in pediatrics, yet effective for some drug-resistant pediatric infections.

The patient was on the state Medicaid insurance and required a so-called prior authorization, or PA, for Ciprofloxacin. Consisting of additional paperwork that physicians are required to fill out before pharmacists can fill prescriptions for certain drugs, PAs boil down to yet another cost-cutting measure implemented by insurers to stand between patients and certain costly drugs.

The PA process usually takes from 48-72 hours, and it’s not infrequent for requests to be denied, even when the physician has demonstrated an undeniable medical need for the drug in question.

Continue reading…

“Remember that Oath?”: EPCS and the Fight Against Opioid Abuse

By SEAN KELLY, MD

As doctors, we all took an oath when we graduated from medical school to “do no harm” to patients. It is, therefore, our duty to speak up and take action when there is an opportunity to prevent harm and improve patient care, safety and well-being. On average, the opioid crisis is killing more Americans on a monthly basis than traumatic injuries. It is time for the medical community to raise its voice even more loudly in support of proven technology that helps curb this crisis.

This month, California Governor Jerry Brown became the latest state lawmaker to embrace electronic prescribing for controlled substances (EPCS) — joining nearly a dozen other states that have passed legislation mandating that health care providers and pharmacies use the technology. The Golden State law was signed at the same time the U.S. Senate passed a bill requiring e-prescriptions for any reimbursement under Medicare Part D.

Clearly, EPCS is emerging as a key tool in the fight against opioid abuse. And legislators aren’t alone in driving the trend — corporations are playing a key role as well. Walmart, one of the nation’s largest pharmacy chains, is requiring EPCS by January 1, 2020. In their press release, it was noted that “E-prescriptions are proven to be less prone to errors, they cannot be altered or copied and are electronically trackable.”

Continue reading…

A Rosa Parks Moment is Coming in Phase 1 Cancer Trials

By DAVID C. NORRIS, MD

I want to tell you about the most exciting discovery I’ve made in 2+ years of research on dose individualization methods for phase 1 cancer trials. This discovery has nothing to do with any of the technical problems I’ve confronted and solved along the way. It involves no gigantic equation, no table of simulations results, and no colorful plot. Rather, it’s a discovery about sources of power to innovate in drug development.

In general, how would you describe the balance of power between Big Pharma and the individual patient? The question seems ludicrous—maybe even offensive—in light of ongoing scandals with price-hikes and shortages for critical drugs. But in the special area of trial methodology, I’ve got a real surprise for you…

One result from my DTAT research has been a clear demonstration that 1-size-fits-all dose finding in phase 1 cancer trials can cut the value of a drug in half, or even drop it to zero by setting the drug up for failure in phase 2 or 3. Although this economic argument has never been made quite so explicit and rigorous, I am certain the underlying principle comes as no surprise to anyone. (I note hardly anyone bats an eye when I detail the math.) Continue reading…

Registration

Forgotten Password?