Reanalysis of a trial used to approve a commonly used injectable cholesterol-lowering drug confirms the original analysis by accident.
The open-data movement seeks to liberate the massive amount of data generated in running clinical trials from the grasp of the academic medical-pharmaceutical industrial complex that mostly runs the most important trials responsible for bringing novel therapeutics to market.
There are only a few elite academic trialist groups capable of running large trials and there’s ample reason to be suspicious about the nexus that has developed between academia and the pharmaceutical companies that shower them with cash to hopefully get a positive study result and pay off the pharmaceutical research investment manifold. The FDA is the major regulator of the whole process, but the expertise required for regulation means that the FDA is frequently comprised of ex-pharma employees or ex-academics.
This week’s headlines seemingly closed a chapter on the story of medical research criminality in America. Ramesh “Sunny” Balwani, former president and COO of Theranos was sentenced to 13 years in prison for fraud. That’s 2 years more than his former business and romantic partner, Elizabeth Holmes.
White crime criminal defense attorney for all things science tech, Michael Weinstein, took the opportunity to trumpet out a confident message that crime doesn’t pay in Medicine with these words, “It clearly sends a signal to Silicon Valley that puffery and fraud and misrepresentation will be prosecuted, there will be consequences and the end result is potentially decades in prison.”
The smooth talking fraudsters played a good hand for years, buoyed by a Board, asleep at the $9 billion valuation wheel, with the likes of George Shultz, Henry Kissinger, Rupert Murdoch and Larry Ellison. But attorney Weinstein and all associated with Health Tech entrepreneurship would do well to read again a classic piece of health journalism from fifty-six years ago.
On June 16, 1966, the New England Journal of Medicine published an article titled “Ethics and Clinical Research.” Written by a highly respected Harvard physician, Henry K. Beecher, the head of anesthesiology at Massachusetts General Hospital, the article referred to “troubling charges” that had grown out of “troubling practices” at “leading medical schools, university hospitals, private hospitals, governmental military departments (the Army, the Navy and the Air Force), governmental institutes (the National Institutes of Health), Veterans Administration hospitals and industry.”
Beecher then reviewed 50 distinct contemporary American clinical studies with ethical violations judged by standards at Beecher’s own Massachusetts General Hospital.
This is “high grandparenting season” at our home when you go “The Extra Mile.” That means it is possible on certain days on or between Thanksgiving and New Year’s Day to find up to 20 children and grandchildren under our roof. With my wife one of ten, and me, one of twelve, we are no strangers to chaos. Our kids believe we feed off it, and maybe they’re right.
With over 150 years under our collective belts, we two are – if nothing else – optimistic, resilient, and somewhat wiser then we were in our early years. For example, we know that the mere temporal or geographic approximation of two incidents or events does not necessarily prove cause and effect.
That point was reinforced the morning after Thanksgiving when our 11 year old granddaughter informed me that the basement toilet was clogged. She then provided a thumbnail sketch of the events the night before after we had bailed early – the toilet overflowed (nobody knows how or why), a frantic search for a plunger failed even though all were enlisted in the effort, and eventually everyone retired satisfied that the now unusable toilet was quiescent.
A recent CNN article discusses approval of the Moderna Covid-19 vaccine for people ages 6-17. The CDC director acted after its vaccine advisers on the Advisory Committee on Immunization Practices voted unanimously to support the two dose Moderna COVID-19 vaccine for kids in this age group. The goal per CDC director Walensky was to “protect our children and teens from the complications of severe COVID-19 disease”
I went for an annual physical with my doctor at One Medical in December. OK it wasn’t actually annual as the last time I went was 2 & 1/2 years ago, but it was covered under the ACA, and my doc Andrew Diamond was bugging me because I’m old & fat. So in I went.
I had a general exam and great chat for about 45 minutes. Then I had blood work & labs (cholesterol, A1C, etc) and a TDAP vaccination as it had been more than 10 years since I’d had one.
Today, about one month later, I got an email asking me to pay One Medical. So being a difficult human, I thought I would go through the process and see how much a consumer can be expected to understand about what they should pay.
Here’s the email from One Medical saying, “you owe us money.”
Not to sound too alarmist, but the radiopharmaceutical industry is on the verge of an explosion. But don’t worry; it’s not the type of explosion one often associates with nuclear materials… I love those movies too! It’s the beginning of a new wave of innovation for the diagnosis and treatment of certain cancers and other diseases.
This new radiopharmaceutical boom quite literally has the life sciences industry in a nuclear arms race of sorts, as companies like Y-mAbs, Novartis and others are pushing through clinical trials for the next blockbuster for the treatment and detection of hard-to-treat diseases like medulloblastoma and metastatic castration-resistant prostate cancer. But all this excitement has many wondering, “what are radiopharmaceuticals anyway?”
Radiopharmaceuticals are simply a group of pharmaceutical drugs containing radioactive isotopes. They are being used primarily for the treatment and detection of certain types of cancers, but they are also being developed for cardiac disease as well. And what makes radiopharmaceuticals so unique is that they can be targeted to extremely precise areas in the human body.
Although gaining ground with more precision today, this type of therapy actually began in the 1940s with I-131 – which has become an important agent for the treatment of benign and malignant thyroid disease. The development of radiolabeled antibodies began in the 1970s, and Radium-223 dichloride was approved by the FDA in 2013 for the treatment of castrate-resistant metastatic prostate cancer. Lu-177 PSMA is one of several recent developments that are making their way through FDA approvals.
“The radiopharmaceutical industry has actually been around for some time, but today it is at a tipping point,” says SpectonRx president Anwer Rizvi. “Over the next few years, it is estimated that our industry will triple. With more radiopharmaceuticals making their way through clinical trials and FDA approval, we are starting to see more data that highlight their effectiveness. This is why we are now starting to see more life sciences organizations committing real resources to radiopharmaceuticals.”
Late one evening, a trauma patient, a mother of three, comes through on an ambulance. She’s having trouble breathing, despite the breathing tube lodged in her throat. Dr. Nikhil K. Murthy, the neurosurgeon on the case, assesses the situation and orders a CT, which reveals a ruptured aneurysm, or a burst blood vessel. Excess fluid in the brain is fatal, as the increased pressure deprives the brain of vital oxygen. A sense of immediacy surges through Dr. Murthy as he calls for the necessary supplies to perform a ventriculostomy to drain the blood. He rushes to connect the drill bit, brace the manual drill against his body, and drill a hole in the right place, at the precise angle and depth. With the urgency of the situation blaring in his mind, Dr. Murthy has only his experience, training, and intuition to ensure that he does not drill past the skull and into the brain. The stakes are high, and a woman’s life is on the table.
Bedside ventriculostomies, like the one described above, are common in the emergency department, as the surgery is often performed in life-or-death situations to immediately relieve fluid build-up in the brain. Dr. Murthy’s experience does not stand alone: countless neurosurgeons have stood in his exact shoes. While Dr. Murthy successfully performed the ventriculostomy, saving the woman’s life, not everyone is as lucky: the complication rate for bedside ventriculostomies in the U.S. stands at an egregious 50 percent.
“When that woman was lying on the table, a drill braced against her skull, what she and I both needed was a safer, more reliable tool to perform the surgery.” – Dr. Nikhil K. Murthy
I recently participated in a debate opposing me to Professor Adam Cifu on the topic of “Evidence-based medicine in the age of COVID.” The debate took place on an episode of Dr. Chadi Nabhan’s Outspoken Oncology podcast. Dr. Saurabh Jha was the moderator and he did a great job keeping us on point and asking for important clarifications when needed. It was a fun and cordial moment and I found it intellectually fruitful. You can listen to it here or on any podcast platform. The discussion strengthened my conviction that the central issue about EBM is the conflation of the role of the physician with that of the clinical scientist.
That conflation was quite apparent in a recent online editorial published by Robert Yeh and colleagues on the topic of equipoise during the COVID-19 pandemic. Yeh at al. are accomplished academic cardiologists and outcomes researchers (Yeh was a guest on The Accad and Koka Report a couple of years ago).
I’ll get to their editorial in a moment, but equipoise is a term that I became aware of only in the last few years, mainly from mentions on MedTwitter. From those mentions I developed an intuitive sense of what equipoise must mean: a mental state of uncertainty about a treatment that prompts the medical community to seek a more definitive answer by way of a randomized controlled trial. For example, one might say “I’m not sure if hydroxychloroquine works to prevent or treat COVID-19. Based on the existing collective experience, there is equipoise about it. We need a clinical trial.”
That seems reasonably straightforward, but the editorial by Yeh et al. piqued my curiosity so I decided to look into the origin of the term and its introduction in the medical literature.
We’re pretty proud of
modern medicine. We’ve accumulated a very intricate understanding of how
our body works, what can go wrong with it, and what are options are for
tinkering with it to improve its health. We’ve got all sorts of tests,
treatments, and pills for it, with more on the way all the time.
However, there has been
increasing awareness of the impact our microbiota has on our health, and I
think modern medicine is reaching the point classical physics did when quantum
physics came along.
pictured the atom as kind of a miniature solar system, with well-defined
particles revolving in definite orbits around the solid nucleus. In
quantum physics, though, particles don’t have specific positions or exact
orbits, combine/recombine, get entangled, and pop in and out of
existence. At the quantum level everything is kind of fuzzy, but quantum
theory itself is astoundingly predictive. We’re fooled into thinking our
macro view of the universe is true, but our perceptions are wrong.
So it may be with modern
medicine. Our microbiota (including both the microbiome and mycobiome) both provide the fuzziness and dictate a significant portion of
The World Health Organization has named 2020 the Year of the Nurse and Midwife. However, most Americans have never experienced a midwife’s care. In my over 30 years working in maternal-child health, I’ve heard plenty of reasons why. Families are understandably nervous about that with which they are unfamiliar, and nervous about pregnancy and birth in general, with good reason. The cesarean birth rate in the US has more than quadrupled since the early 1970’s, yet we aren’t seeing healthier mothers and babies as a result. In fact, compared to the prior generation, women in this country are 50% more likely to die in childbirth, and for women of color (particularly black women) that risk is three to four times higher than white women, regardless of the woman’s education level or socioeconomic status. For those expecting a baby in the new year, let me set the record straight about midwifery care.
Today’s certified nurse-midwives (CNM) and certified midwives (CM) have earned a minimum of a Master’s degree, as well as have passed a rigorous certification exam. A third category, certified professional midwives, are not required to have an academic degree, but they must also must pass a certification exam “based on demonstrated competency in specified areas of knowledge and skills.” Midwives are intensely educated both in normal, as well as in complications of, pregnancy and childbirth, and are well-prepared to address emergencies as they arise.
Midwives generally care for women with low-risk pregnancies; however, most pregnancies arelow-risk. And in those instances when a patient’s pregnancy or birth becomes high-risk, the midwife collaborates with physician colleagues to provide comprehensive team care to result in the best outcome for mother and baby.