FDA Archives - Marilyn Singleton, MD JD

COVID-19, Current Events, Guest Column, Politics, Uncategorized, What's New

COVID-19: Notes from FDA Vaccine Approval Hearing

December 14, 2020 No Comments

Jane Orient, MD — December 14, 2020

If you are in the first allocation group, you might be lining up for your COVID-19 vaccine.

The Pfizer messenger RNA (mRNA) vaccine was approved by the Food and Drug Administration (FDA) under an Emergency Use Authorization (EUA) after a 9-hour advisory committee meeting on Dec 10. The Moderna vaccine may follow soon.

Committee members were presented the question: “Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?”

Here are some highlights from the hearing:

A number of committee members noted that the vaccine trial produced measurable antibodies by lab assay, but the evidence that it reduced clinical COVID-19 was sparse.

Several committee members objected to the inclusion of 16-to-18-year-olds. This objection was because of the lack of trial data from this age group, and the relatively low reported risk of adverse outcomes in COVID-19 disease in this age group. The response was that inclusion of this age group in the initial approval would allow for future stepwise inclusion of yet younger ages, leading eventually to the incorporation into the standard regimen of childhood vaccinations.

Another concern was the lack of data on the incidence of longer term adverse events, possibly auto-immune in nature, given that mRNA is an untested technology. Pfizer representatives were asked whether they had prepared additional follow up data since the 2-month data was now a month old. They said that they had not made an interval assessment, as that was not required in the FDA process. The original filing was very burdensome, they noted.

Several committee members suggested limiting the authorization to high-risk groups, thus providing for a better benefit-to-risk profile, when risk was unknown. The response was that, because of logistics, initially only high risk groups would get the first available doses, and we would know more in the spring.

On a vote of 17-5, the committee answered the proposed question in the affirmative. After the vote, the chair abruptly adjourned the meeting without the previously promised second vote on whether to insert the words “to date” after “evidence.”

Adverse events (AEs) that were solicited occurred in 18.7% of vaccine recipients vs. 3.9% in the placebo group. Unsolicited, “non-serious” AEs included swollen lymph nodes in 64 with vaccine and 6 with placebo, and Bell’s palsy (see graphic) in 4 with vaccine and 0 with placebo. For the palsy, there was said to be no clear basis for concluding a causal relationship at this time, and that the frequency was consistent with the background rate in the population.

Doctors are being encouraged to take selfies when they get vaccinated to use in a promotional campaign on social media.

If you would like to discuss these issues, contact me at janeorientmd@gmail.com or (520) 323-3110.

Jane M. Orient, M.D.

Executive Director, Association of American Physicians and Surgeons

This drawing of a Canadian (Ojibway) Indian mask called “Broken Nose” demonstrates the classic features of Bell palsy: loss of forehead wrinkling, deviation of the mouth to the nonparalyzed side, sagging of the paralyzed side with loss of the nasolabial crease, and the rounder eye suggesting the failure of the upper eyelid to move down when the patient is asked to close his eyes (drawing by William Snavely).–

COVID-19, Current Events, Featured, Medicine, Op-eds, What's New

Will the FDA Find Courage in the Age of COVID-19?

March 23, 2020 No Comments

By Marilyn M. Singleton, MD, JD

While on lockdown to save our neighbors from a lonely death from the disease called CoViD-19, many of us have turned to movies. I beg you not to rent Pandemic, Contagion, or 28 Days Later. Try Harriet instead. Harriet Tubman was the epitome of bravery and courage in the face of insurmountable odds. Her escape from slavery and returning again and again into the belly of the beast to save others should inspire us all. The health professionals working day and night to care for an ever increasing number of sick patients make me proud to be a doctor. And kudos to the grocery store workers, postal workers, police and many others who are performing essential jobs with a smile.

This is the time for positive action, not panic. For background, coronaviruses are a big family of RNA viruses named for the crown-like spikes found on their surface. They exist around the world cause mostly upper respiratory tract infections (“common colds”) in adults. This new coronavirus is in the same family as the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) identified in humans in 2002 and Middle East Respiratory Syndrome coronavirus (MERS-CoV) identified in 2012. The CoViD-19 virus is called SARS-CoV-2 for its similarity to SARS-CoV.

While scientists are furiously experimenting with possible vaccines, the virus is sprinting from country to country despite travel restrictions. There are likely among us “healthy carriers” of the virus who have no signs or symptoms of the disease but can infect others. So if CoViD-19 is here for a while, the world has to look to effective treatments of afflicted individuals today—not a year from now. Some researchers seem to have found a strong contender.

Separate studies from a major medical center in France and jointly from South Korea and China have found that inexpensive, readily available anti-malarial drugs chloroquine phosphate or hydroxychloroquine are an effective treatment. But the Federal Drug Administration (FDA) is dragging its feet, despite the President’s urgings, to approve the drug for anti-viral use. Dr. Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and the White House’s advisor has dismissively called the studies “anecdotal” meaning “based on or consisting of reports or observations of usually unscientific observers.”

In 2004, separately a Belgian virologist and our Centers for Disease Control and Prevention found that chloroquine inhibited SARS-CoV growth in primate cells when given before or after exposure to the virus. Human trials could not be done because thankfully the SARS epidemic had just ended. Fast forward to February 2019. In South Korea, these drugs were given by physicians and scientists in the CoViD-19 Central Clinical Task Force. These studies showed “certain curative effect” with “fairly good efficacy.” Further, patients treated with chloroquine demonstrated a better drop in fever, improvement of lung CT scan images, and required a shorter time to recover compared to parallel groups.

More promising is a study of 36 patients actively ill from CoViD-19 by a noted research team from France. Of the 20 patients treated with hydroxychloroquine alone, 70 percent had no detectable virus within 6 days; those treated with hydroxychloroquine and azithromycin (an antibiotic with some anti-viral action) had a 100 percent success rate. Yes, the study is small, but these are extraordinary times.

On March 22, Gov. Cuomo announced that the FDA is allowing New York state to start a trial of hydroxychloroquine and azithromycin. Let’s move on this!

Chloroquine and hydroxychloroquine are approved by the FDA for malaria, rheumatoid arthritis, and systemic lupus erythematosus. The FDA is well aware that physicians prescribe plenty of drugs that are “off label,” that is drugs approved by the FDA for other conditions. Indeed, one fifth of all prescriptions are off label. For example, aspirin was approved for pain relief, but had many years of off-label success for the prevention of heart attacks before the FDA finally approved the off-label use.

Mike Tyson said “we all have a plan until we are punched in the face.” FDA’s “plan” is to regulate products and promote safe and effective drugs. This is the FDA’s moment to bravely keep us safe by shifting gears and deregulating a valuable product. Pharmacists must be allowed to fill such prescriptions. Let doctors do what they do best: use their independent judgment. Let physicians consult with their patients and let them choose to take the off-label medicine, or approved anti-viral medicines that have failed against CoViD-19 in studies—or no treatment at all.

While people are struggling to pay for their next meal, we need bold action now. For 6 billion dollars all Americans could be treated—saving hundreds of billions of dollars in lost income and retirement savings.

Bayer began with donating 3 million tablets to our government. More companies are stepping up. Novartis has pledged a global donation of up to 130 million hydroxychloroquine tablets, pending regulatory approvals for COVID-19. Mylan is increasing production in West Virginia to make 50 million tablets. Teva is donating 6 million tablets to hospitals around the U.S. For context, each patient’s treatment would use up to14 tablets.

Do your job, FDA and protect the public. Approve hydroxychloroquine now for COVID-19. Meanwhile, physicians may legally prescribe these drugs because they are approved for other indications.

Bio: Dr. Singleton is a board-certified anesthesiologist. She is Immediate Past President of the Association of American Physicians and Surgeons (AAPS). She graduated from Stanford and earned her MD at UCSF Medical School. Dr. Singleton completed 2 years of Surgery residency at UCSF, then her Anesthesia residency at Harvard’s Beth Israel Hospital. While still working in the operating room, she attended UC Berkeley Law School, focusing on constitutional law and administrative law. She interned at the National Health Law Project and practiced insurance and health law. She teaches classes in the recognition of elder abuse and constitutional law for non-lawyers.

Book Reviews, Health Policy, Medicine, Socialized Medicine

Book Review: China Rx: Exposing the Risks of America’s Dependence on China for Medicine

June 8, 2019 No Comments

by Rosemary Gibson and Janardan Prasad Singh, ISBN 9781633883819, Prometheus Books, 2018.

“Without firing a missile or hacking the electric grid, China can take America down by disrupting access to essential drugs,” write the authors of this important book.

This book is a fine piece of investigative journalism that educates the reader about the genesis of China’s grip on our supply of medications. China is now the largest global supplier of the active ingredients and chemical building blocks needed to make many vitamins, and prescription and over-the-counter drugs. These include antibiotics, steroids, and cancer drugs.

Until the mid-1990s, the U.S., Europe, and Japan manufactured 90 percent of the global supply of key ingredients for the world’s medications. Now more than half of the 4,000 active ingredients needed to make a make a pharmaceutical depend on China.

Our weakness for bargains has created a monster. The authors note that hospitals and retail pharmacies have become “like the big box stores, stocked with made- in-China items.” China’s winning formula is for a company—with the help of the government—to undercut the price of drugs or components; the artificially low price forces other companies out of the market; then the company is free to manipulate the price and supply at will.

But the authors warn that “cheaper drugs required a cheaper way to make them.” A light was shined on China’s poor manufacturing practices of ingestibles in 2007 with the well-publicized dog and cat-food recall. More than 4,000 pets died from renal failure due to contamination with melamine, an industrial chemical used in plastics manufacture.

The outrage over this “economically motivated contamination” of pet food dissipated while in the next year a far less-publicized drug contamination took human lives. Although “manufactured” by an American company (Baxter Healthcare Corporation), heparin was made in China under substandard conditions and was sold to unwitting hospitals with tragic consequences. One-third of the batches of heparin from China were contaminated. The book fully explores the heparin debacle, telling how it happened and what our government has done about protecting us in the future.

From the start, the authors received robotic, scripted, unhelpful replies to the straightforward question: where was this drug made? Searching for the answer, the authors delve into the loopholes in treaties and Food and Drug Administration (FDA) regulations that have allowed shoddily manufactured drugs for human consumption to be used in the U.S. Moreover, politics was interjected. The Transparency in Drug Labeling Act was introduced in 2008 to force drug labels to disclose where the drug was produced, not merely the location of the parent company. The law went nowhere, and it appears that the power of the drug company lobbyists prevailed over safety. Did this signal to China that the U.S. could be influenced by special interests, sometimes to the detriment of its populace?

China’s latest Five-year Plan for National and Social Development includes entering (and cornering?) the market on medical devices. The centralization of global supply in China leaves the world vulnerable. Not only can they disrupt the supply chain and cause shortages but purposefully create shortages or adulterate drugs. Keep in mind, the active ingredient for ciprofloxin to treat anthrax is in China’s hands.

This meticulously researched book is disturbing, but it is required reading for anyone who takes or prescribes medications. It is a real page-turner that reads like a novel and includes real-world scenarios. The authors included a detailed index, making the information readily accessible for repeated reading.

The Chinese think ahead with their well-known “five-year plans.”This book is a wake-up call for America to start planning for our future as well.

Review by Marilyn M. Singleton, M.D., J.D., Redondo Beach, Calif.

Purchase Book at: https://amzn.to/2IygpYD