Sunday, May 26, 2019

The $2 million cure

You can save your baby for $2 million. Can you afford to do this? If you cannot, should we all pay?
Spinal muscular atrophy (SMA) is a rare genetic disease affecting the part of the nervous system that controls voluntary muscle movement. All types of SMA result from a single known cause, a deficiency of a protein called SMN, for "survival of motor neuron." When SMA symptoms are present at birth or by the age of 6 months, the disease is called type 1 SMA (also called Werdnig-Hoffmann disease). Babies with SMA Type 1 typically have generalized muscle weakness, a weak cry and breathing distress. They often have difficulty swallowing and sucking, and don't reach the developmental milestone of being able to sit up unassisted. These babies have two copies of the SMN2 gene, one on each chromosome 5. Over half of all new SMA cases are SMA type 1. It is a horrible disease; untreated, half of all affected infants will not live to one year of age, or if alive will require a ventilator (breathing machine). The disease affects about one in every 10,000 births, so there are about 300-400 babies born each year in the United States with this up-until-now fatal disease.
On May 24, the FDA approved a gene-based therapy for SMA-1 called Zolgensma, developed by a company that was bought by Novartis. The therapy involves injecting affected babies with an adenovirus containing a copy of the correct gene, that is taken up by the babies’ spine and theoretically cures the disease permanently. The trial which led to FDA approval was done on 22 affected babies; it showed that 21 of 22 were alive and reaching expected developmental milestones at 9.5 months of age. Untreated, 50% of these babies would not be expected to be alive at one year. For the parents of these babies, a miracle. The only fly in the ointment was that Novartis announced the treatment would be priced at $2.125 million! The only previously-approved gene therapy for an inherited disease was approved in 2017 for a rare, previously untreatable, eye disorder leading to blindness. This was priced at $425,000 for each eye. These two treatments promise (though long-term results are many years away) to cure a disease. We are now also starting to see new drugs to treat uncommon and hard-to-treat diseases that are not cures but which carry a sky-high price tag. One is Orkambi, used to treat cystic fibrosis, a hereditary disease that is treated much more easily than it used to be, though children with it are still prone to repeated lung infections. This drug clearly improves the course of patients with cystic fibrosis, but modestly, and is priced at $250,000 a year and must be taken indefinitely.
The focus of lawmakers has been, not surprisingly, on common drugs that are seeing steady price rises well above inflation, and which are taken by millions of people. Insulin is the classic example. Its price has resulted in diabetics skipping their doses and getting sicker or even dying, and this for a drug that has been in use since 1922. While pharmaceutical companies have tweaked the molecule, there have been no breakthroughs. I believe that there is enough outrage that Washington will convince or force the pharmaceutical industry to at least moderate their price increases.
What we have not yet come to grips with is how to deal with the astronomical prices of the new “breakthrough” drugs such as Zolgensma. It is hard to see a health insurer refusing to pay for a truly life saving drug. Among the many problems to be faced are how an insurance company deals with the fact that they may be paying for a drug for a patient who will not be even in their plan next year; is it fair to them? What happens if the miracle loses its luster a few years down the road. The results for Zolgensma are after less than a year of use. What happens if the effect wears off? Does Novartis have to refund some or all of the money? If we treat 350 babies a year, we are talking $700 million/year – and the U.S. already spends too much on health care. Does that money come at the price of bridges falling down? Since many of these new gene-based therapies grew out of public (NIH) funded research, it is reasonable for our elected representatives to negotiate a “fair” price that takes this into account and does not simply allow big pharma to enrich its executives and shareholders.
You remember that old Chinese curse: “may you live in interesting times.” Well, hold onto your hats. The next few years will be very interesting.

Prescription for Bankruptcy. Buy the book on Amazon

Sunday, May 19, 2019

Baby, its later than you think

A recent New York Times Op-Ed piece had the catchy title “Don’t see your doctor in the afternoon.” It was prompted by a study published in JAMA Network Open that had the much less catchy title “Association of Primary Care Clinic Appointment Time with Clinician Ordering and Patient Completion of Breast and Colorectal Cancer Screening.” The study found that the frequency of appropriate ordering of mammograms was highest (64%) for patients with 8 AM appointments and lowest (48%) for those seen at 5 PM. Similar results were seen for colorectal cancer screening, (36.5% at 8 AM and 23.4% at 5 PM). [Why so much lower for colon cancer screening is a subject for another day.] Patients did not follow through with all the recommended testing, but the trend was the same, with more patients completing the recommended tests if they had early morning appointments.
Why is this? Part of it is simple fatigue as the day goes on. Similar results were found when the National Highway Safety Administration looked at when most fatal traffic accidents occur. The evening, but not the morning, rush hour saw the greatest number of fatal accidents. Decision fatigue is used at car dealerships, where the most expensive and unnecessary options tend to be given at the end of a series of choices. Doctors, believe it or not, are human. We get tired as the day goes on, and fatigue clearly has a negative effect on decision-making. There is also the factor that primary care doctors these days have impossible workloads, with more things to be crammed into a 10-15-minute visit than can possibly be done, and the ever-lurking electronic record and its insatiable demands for data making things worse. We know that talking someone into a screening test takes time, and it is much easier to do this before we are already half an hour behind schedule.
While not recommending a screening test can be made up at a later visit, I strongly suspect that other forms of decision-making also suffer as the day goes on. It is much easier to prescribe an antibiotic that we know is not needed than to explain why the patient would be much better without it. I don’t have the data, but I would be willing to wager that more diagnostic errors are made on the last patients of the day than the first.
What can be done? Ideally, doctors would have more time for a visit and not be so rushed. In the real world, when you are scheduling your next visit, try hard to make it early in the day, before your doctor is too tired to think optimally.

Prescription for Bankruptcy. Buy the book on Amazon

Monday, May 13, 2019

Doctor - could I have Alzheimer's disease?

As my patients aged along with me, I noticed both the expected increased numbers of people with some form of dementia and even more patients who were worried about this topic. Unless you have been away on a ten-year safari, you are very aware that dementia is a growing problem. Some 5.8 million Americans are living with Alzheimer’s Disease, and similar numbers occur in most western countries. The incidence goes up with age, and we are living longer. As I responded to a questioner recently, the only way I know of to avoid getting the disease is to die young (which I don’t recommend as a preventive strategy).
The subject gets complicated because normal aging is often accompanied by some mild memory loss. A not-unfamiliar dialog between a couple in their 70’s might be: “I was thinking we might watch a movie – the one with that actress we both like.” ”The one that starts with M?” “Yes, Meryl.” Which movie?” “Oh, the one we thought was out of her usual.” “You mean that comedy?” “Yes, about a wedding.” “OK – the Abba musical.” “That’s the one!” Mild changes in memory or less ability to quickly learn new facts are both common as we age and do not usually interfere with functioning.
There is also a condition called “mild cognitive impairment” (MCI) in which the changes in thinking and memory are more than one would expect with normal aging but not severe enough to be called dementia. The latter usually includes both memory loss and some other symptoms such as trouble with word-finding, getting lost in familiar places, inability to cope with unexpected events or handling complex tasks. Some, but by no means all, people with MCI will go on to dementia and doctors really cannot predict which will.
If a person appears to have dementia, the task of the primary care physician, often with the help of a neurologist, is to decide what is causing the dementia. While Alzheimer’s Disease is the most common, there are a variety of other brain diseases that can cause dementia. While there are some clues to be gotten from detailed brain imaging, particularly the PET scan, Alzheimer’s is in essence a clinical diagnosis, as there are no blood tests that can be used. It is important to not overlook the treatable causes of dementia. Depression can cause a “pseudo-dementia,” and a variety of medications can do this, including many that are used by the elderly. Both B12 deficiency and an underactive thyroid can cause dementia; while infrequent, testing for these is easy and reliable and should always be done once.
To complicate matters, a group of neurologists specializing in dementia have recently proposed that, particularly in the oldest group, over 80, a newly described condition they call LATE, for “limbic-predominant age-related TDP-43 encephalopathy,” may be even more common than Alzheimer’s and may co-exist with it. Their main reason for bringing this to doctors’ attention is that this condition does not respond to the medications used now to slow the progression of Alzheimer’s. The main reason in general to try to make a specific diagnosis is to guide treatment. There are no cures for Alzheimer’s or most of the other dementing illnesses. The medications we have are modestly useful in slowing the inevitable progression of the disease, but that is all they do.
Can you ward off Alzheimer’s without dying young? About all we know is that regular exercise does lower the incidence of dementia, and that a healthy plant-based diet also has modest protective effect. Keeping the brain busy by learning new things is also probably helpful.
So, if your only problem is occasionally forgetting where you left the keys but do find them, you can relax. You probably do not have Alzheimer’s. Get out there and exercise, eat healthy and learn a new language.

Prescription for Bankruptcy. Buy the book on Amazon

Saturday, May 4, 2019

Who is to do the rationing?

One of the arguments made against adopting single-payer health care in this country is that it would “lead to rationing.” This assumes that we lucky people in the US have unlimited access to whatever health care we need and are at risk of losing it. This argument came to mind when I saw a few recent news items. One was that a federal judge, US District Judge Robert Scola, recused himself from a case in which a cancer patient was suing United Healthcare for their refusal to cover the recommended proton beam therapy for his prostate cancer. Judge Scola said he could not rule on the case impartially because he himself had been treated for prostate cancer and had been offered proton beam therapy (though he ultimately chose surgery). In his order of recusal, he wrote “To deny a patient this treatment, if it is available, is immoral and barbaric.” Saturday’s Boston Globe featured an article about a young woman with advanced cancer of the cervix who was referred to Mass General Hospital for proton beam therapy whose insurer refused to pay for the treatment despite multiple appeals.
Moving from anecdotes to a larger sample (and I am well aware that the plural of anecdote is not data), I found a survey conducted among radiation oncologists this Spring. Nine out of ten said their patients faced delays in getting recommended therapy for their cancers. Almost a third (31%) said that such delays lasted more than five days, the equivalent of a standard week of therapy. The reason that this is important is that for every week therapy is delayed, there is about a 2% increase in mortality. Almost two thirds (62%) said that the denials were ultimately overturned on appeal, making one wonder why the therapy was denied in the first place. Having been harassed for years by insurance company clerks over getting approval for tests and treatments, I have my own theory, which is that the insurer hopes that blanket denials will weed out many expenses, as the doctor will be too busy or frustrated to spend the time to appeal, thus saving the insurer money. As I note in Prescription for Bankruptcy, an AMA survey in 2018 of 1,000 physicians found that 92 percent felt that prior authorization programs delay access to care, with 78 percent saying that prior authorization causes some patients to abandon recommended tests or treatments. Maddeningly, 30 percent said they had waited three or more days to get a decision from the insurance company. The radiation therapists noted that when their appeals reached the point of speaking to a “peer,” the physician with whom they spoke was almost never in that field and often demonstrated little knowledge of the problem being addressed. Put this together with Aetna’s recent settlement of a lawsuit alleging that their physician reviewers rarely even read the patients’ records before issuing denials, and one sees a pattern. While there is room for legitimate disagreement about the value of some therapies, it is inappropriate for the insurer, with a clear financial stake in the decision, to be the decision-maker about what tests and therapies are covered. In any rational health care system, the determination about paying for a procedure would be made by disinterested experts who could look at the scientific evidence and make a recommendation with no financial stake in the outcome.
Rationing? We have rationing now, but the rationing is done by those who save money from doing this. In my ideal system, patients, clinicians and statisticians would make evidence-informed guidelines. In the absence of such a rational process, I would rather this be done by “bureaucrats” than by the for-profit insurers as it is now.

Prescription for Bankruptcy. Buy the book on Amazon