Tag: FDA

A New Day for Parkinson’s Disease Research Is Near


The U.S. Department of Health and Human Service (“HHS”) is responsible for a wide range of activities relating to medical and public health. It has 60,000 employees and a $1.7 trillion annual budget with approximately $140 billion for discretionary spending. For the past 13 years, HHS has been spearheading a National Plan for addressing Alzheimer’s disease – with some notable successes.

Given its resources, expertise and charter, HHS should launch a National Plan to cure Parkinson’s disease patterned after its approach on Alzheimer’s disease.

Legislation, or Not

The U.S. House of Representatives has passed H.R.2365, the National Plan to Cure Parkinson’s Disease.

The bill would establish HHS as the central point for strategic direction and coordination of PD research.  It would require formation of a broad-based Advisory Panel to provide strategic advice and any on-going course corrections.

There is nothing preventing HHS from putting the structure of H.R. 2365 into effect now, and it should do so without waiting for Senate action or inaction. There is no incremental funding required to implement this National Plan, nor is any Congressional approval necessary.  This approach would mark an important step towards finding a cure for Parkinson’s disease, and is well within HHS’s charter.

A Cross-Section of Policy and PD Research

For those who have studied the application of regulatory policies to Parkinson’s disease research, it does not provide a productive narrative.

Levodopa was first discovered in 1910. In 1975, after 14 years of its “miraculous” treatment of PD symptoms, the FDA approved the drug. Levodopa does not cure or delay the progression of the disease. Yet, it has remained the gold standard of treatment of PD for the past fifty years. That is not to say there has been insufficient research or inadequate FDA approvals.  Rather, it’s a question of where the research dollars have been funneled. It turns out that levodopa becomes less effective over time and eventually produces uncontrolled shaking. Therefore, research dollars have been targeted toward drugs that delayed the need for levodopa or controlled its side effects.

An exception to this approach was Geron, which became a leader in embryonic stem cell research. It had raised $100 million to conduct clinical trials. However, most of that money was consumed by undertaking thousands of experiments on mice under the “guidance” of the FDA. Nevertheless, Congress saw the potential of embryonic stem cells, and passed the Stem Cell Research Enhancement Act.

While Congress cheered, the Evangelical movement viewed embryonic stem cell research as barbaric and akin to murdering a human life. It didn’t matter that embryonic stem cells could not become a living being unless they were implanted in a woman’s womb, and this step wasn’t part of the research efforts.  Notwithstanding, the Evangelicals convinced George W. Bush to veto the legislation, and a promising path for PD research was shut down.

More recently, the House has passed bills for a National Plan to Cure Parkinson’s in its last two sessions, but the Senate has failed to act, despite a myriad of sponsors of a bill with similar provisions.

Building Upon Lessons from the Past

In 2011, Congress passed legislation establishing a National Plan to Address Alzheimer’s disease (“NAPA”).  Thirteen years later, there are many lessons to be learned from that effort that can be applied in a National Plan for PD. Of particular note, the original plan had five objectives including to “Prevent and Effectively Treat AD/ADRD by 2025”. 

The first report by the Advisory Council specified that the current “level of resource commitment falls drastically short of the funding needed to accelerate the pace of research on prevention, cures, and treatments for AD”. It also recommended that the Secretary examine “[h]ow HHS uses existing authorities to reduce drug development barriers and accelerate development of new therapies” and specifically called for recommendations to “accelerate the FDA review process”.

What happened?  While funding was increased substantially and hundreds of potential treatments have been identified, only two drugs have been approved by the FDA under an “accelerated” review process.

While HHS may express pride in the accomplishments from the Alzheimer’s National Plan, it should conclude that the process to get an effective treatment identified and approved takes too long. For example, the FDA provides “guidance” to researchers even before clinical trials are submitted. It also regulates the provision of genetic tests. These actions needlessly slow development and reduce innovation.  

Similarly, the FDA’s regulation of Phase 1 and Phase 2 trials slows down development and does little to benefit the public interest. The FDA points to multiple ways that it has accelerated the drug approval process.  But the reality is that progress from PD research has been lacking.

On the other hand, in 2019, researchers issued a report – based on real-world observations — that Terazosin resulted in a lower incidence of PD and a slower development of the disease when it did occur.  Terazosin has been used for over 35 years to treat other maladies. Yet the drug underwent a 13-person Phase I trial to determine if it is safe. This phase 1 trial took several years to complete. This approach was a distraction that caused unnecessary delay and cost under the FDA’s regulatory regime.

The FDA will say that its rules do not require 3 (or more) trials nor does it mandate a particular trial design. This is disingenuous. Companies spending hundreds of millions of dollars on research cannot afford the risk of shirking the FDA’s standard procedures.

Taken as a whole, the HHS should limit the FDA’s involvement in PD research to approval of Phase 3 trials. Such an approval process will speed development and foster innovation yet maintain adequate safety controls by the FDA. Research organizations would be less constrained in developing their strategies and would be held to more responsibility for their approach to research.

A Multivariate Solution Is Likely to be Required

PD is a complex disease that has different manifestations when looked at from a genetic, diet, exercise, environmental (pesticides/pollution/solvents), vitamin, drug, electronic, radiation and possibly other perspectives. As such, a multivariate solution is likely to be required to successfully treat PD. 

Such a solution will not be well accommodated by the current FDA review process, with each different combination of therapies being subjected to regulatory review and intervention.  The process could drag on for decades.

HHS should recognize the need for a multivariate solution and plan accordingly, as described below.

Data Collection to Identify Multivariate Solutions

In 2010, The Michael J. Fox Foundation launched the Parkinson’s Progression Markers Initiative (PPMI) to find the biological markers of Parkinson’s onset and its progression. That study led to the impressive finding of a tool that can detect pathology not only of people diagnosed with Parkinson’s, but also in individuals that are at a high risk of developing it. However, after ten years, that study has only a few thousand participants. HHS should endorse and expand the scope of that study.

The “second version” of PPMI should be an overlay study designed with the end game in mind. That is, it should produce a mapping of individual people’s PD “score” over time against all relevant explanatory variables that could possibly impact PD for each individual. Such an approach is superior for identifying multivariate solutions.

To accomplish this objective, each participant would establish and maintain a unique portal for his/her own explanatory PD variables. The portal would include a series of hard-coded entry requirements covering scores of inputs. The initial set-up could be completed in piece-part (with the availability of outside assistance) and would auto-populate with each quarterly update (allowing for input of any changes that occurred after the initial set-up). The portal would interface with the growing number of portals of individual healthcare providers and would collect the diagnostic information from those systems. Personal “meters” of this sort are now actively being deployed in the field of Alzheimer’s disease given that certain therapies and drugs have shown progress against that disease.

As the above information from participants is collected over time, artificial intelligence software would be used to identify combinations of diet, exercise, supplements, genetics, sleep habits, therapies, electronics, radiation and drugs that point towards promising results. New treatments such as those undertaken in clinical trials would be added to the participant’s portal as they as are pursued by those individuals. All of the patient’s existing drugs would be analyzed in the context of all other relevant explanatory variables for that participant – over time.

As importantly, a comparative, quantifiable measurement of PD over time for each individual is required. The PPMI was originally focused on identifying a marker for PD and therefore uses a series of qualitative questions to gauge the patient’s development of PD symptoms over time. In contrast, the emphasis for this data collection effort should shift to the explanatory variables affecting PD progression over time.

In terms of the participant’s PD score, I believe a modified version of the Fitness program currently designed for the computer game “Wii” (which provides a quantitative estimate of an adult’s age based on how that person performed on certain activities) would provide more reliable results. Each participant would provide his/her own age estimator from the computer program on a quarterly basis as well as provide any updates for the various explanatory variables.

Once this revised format is established, the HHS should establish a goal of enrolling 100,000 PD participants into the study within two years.

A Better Approach for PD Research Is Available Now

HHS can – on its own accord – dramatically improve the efficiency and effectiveness of Parkinson’s research by: 1) adopting the industry-wide structure it utilized for Alzheimer’s disease, 2) embracing and expanding upon the current PPMI study and 3) limiting the FDA’s involvement in research to the approval of Phase 3 clinical trials.

Steve Zecola sold his web application and hosting business when he was diagnosed with Parkinson’s disease twenty three years ago.  Since then, he has run a consulting practice, taught in graduate business school, and exercised extensively

Zap Away


Speaking as a sometimes forgetful “senior citizen,” when I found out that non-invasively zapping brains with electricity can result in measurable improvements in memory, that’s something I’m going to remember.

I hope.  

In research published in Nature Neuroscience by Grover, et. al., a team lead by Boston University cognitive neuroscientist Robert Reinhart produced improvements in both long-term and short-term (working) memory through a series of weak electric stimulation – transcranial alternating current stimulation (tACS). The authors modestly claim: “Together, these findings suggest that memory function can be selectively and sustainably improved in older adults through modulation of functionally specific brain rhythms.”

The study provided the stimulation using something that looks like a swimming cap with electrodes, applied for twenty minutes a day for four days.  The population was 150 people, broken up into three separate experiments, all ages 65 to 88.

The results were amazing.  “We can watch the memory improvements accumulate … with each passing day,” Dr. Reinhart marveled.  

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Pharmacists Can Now Prescribe Paxlovid. Good idea?


Apparently, the US Food and Drug Administration (FDA), that has long been charged with the safety and efficacy of drugs and devices now also controls who can prescribe drugs.

I was under the mistaken impression that in our highly rule based society you would need to pass a law to allow that to happen. Passing laws , of course, can be a long, messy, process that involves having to convince constituencies, and ruling by executive order is just way more efficient apparently.

So by decree of the FDA patients can now get Paxlovid, an anti-viral for the virus that causes COVID19, “directly from their state licensed pharmacist” if they so choose. Apparently, someone in government decided that there wasn’t enough Paxlovid being prescribed, and the major rate limiting step for many patients is not having access to a provider to prescribe the drug. I have to say provider now because physicians long ago lost the monopoly they enjoyed for prescribing medications to nurses with advanced degrees and physician assistants. The next obvious step is to cut out the ‘clinicians’ completely by allowing patients to get medications from a pharmacist without a prescription.

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Lou Lasagna and the MIC “Integrated Career Ladder” – More Than Just A “Revolving Door.”


The New York Times recently shined a light on the FDA’s top science regulator of the tobacco industry, Matt Holman, who announced his retirement after 20 years to join Phillip Morris. As they noted, “To critics, Dr. Holman’s move is a particularly concerning example of the ‘revolving door’ between federal officials and the industries they regulate…”

As a Medical Historian, I’ve never been a fan of the casual “revolving door” metaphor because it doesn’t quite capture the highly structured and deliberate attempts of a variety of academic medical scientists over a number of decades in the 2nd half of the 20th century to establish and reward an “integrated career ladder” that connected academic medicine, industry and the government. 

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The FDA’s Culture: Should Safety Dominate All Practices?


An organization’s culture is an internal set of shared values, attitudes and practices. The cohesiveness of the organizational culture will affect whether the entity will meet its vision, purpose, and goals.

One type of organizational culture is hierarchical in nature.   Unlike a risk-taking culture, this structure features policy, process and precision. It is best suited for mature and stable organizations.

The disadvantage of a hierarchal culture is that its stability and control can turn into rigidity. In many cases, the organization develops a negative attitude towards ideas supplied by third parties. It paints itself as having the perfect answer for every issue, no matter how large or small.

My interactions with the FDA suggest that its cultural practices are focused on safety, seemingly to the exclusion of all other issues.  This practice may be appropriate in the regulation of food, but not for drug research where flexibility and creativity are required to cure complex diseases.

Over the past decade, I have witnessed an excessive adherence to its existing practices in the context of BRCA1-related breast cancer, metastatic cancer, precision medicines, “Big Data” and Parkinson’s disease. While the rulings were directed at me, the FDA’s position on these issues has impacted millions of people for the worse.

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Pandemic Fears: What the AIDS Battle Should Teach Us About COVID-19


As the globe faces a novel, highly transmissible, lethal virus, I am most struck by a medicine cabinet that is embarrassingly empty for doctors in this battle.  This means much of the debate centers on mitigation of spread of the virus.  Tempers flare over discussions on travel bans, social distancing, and self quarantines, yet the inescapable fact remains that the medical community can do little more than support the varying fractions of patients who progress from mild to severe and life threatening disease.  This isn’t meant to minimize the massive efforts brought to bear to keep patients alive by health care workers but those massive efforts to support failing organs in the severely ill are in large part because we lack any effective therapy to combat the virus.  It is akin to taking care of patients with bacterial infections in an era before antibiotics, or HIV/AIDS in an era before anti-retroviral therapy.  

It should be a familiar feeling for at least one of the leading physicians charged with managing the current crisis – Dr. Anthony Fauci.  Dr. Fauci started as an immunologist at the NIH in the 1960s and quickly made breakthroughs in previously fatal diseases marked by an overactive immune response.  Strange reports of a new disease that was sweeping through the gay community in the early 1980’s caused him to shift focus to join the great battle against the AIDS epidemic. 

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The FDA Needs to Set Standards for Using Artificial Intelligence in Drug Development


Artificial intelligence has become a crucial part of our technological infrastructure and the brain underlying many consumer devices. In less than a decade, machine learning algorithms based on deep neural networks evolved from recognizing cats in videos to enabling your smartphone to perform real-time translation between 27 different languages. This progress has sparked the use of AI in drug discovery and development.

Artificial intelligence can improve efficiency and outcomes in drug development across therapeutic areas. For example, companies are developing AI technologies that hold the promise of preventing serious adverse events in clinical trials by identifying high-risk individuals before they enroll. Clinical trials could be made more efficient by using artificial intelligence to incorporate other data sources, such as historical control arms or real-world data. AI technologies could also be used to magnify therapeutic responses by identifying biomarkers that enable precise targeting of patient subpopulations in complex indications.

Innovation in each of these areas would provide substantial benefits to those who volunteer to take part in trials, not to mention downstream benefits to the ultimate users of new medicines.

Misapplication of these technologies, however, can have unintended harmful consequences. To see how a good idea can turn bad, just look at what’s happened with social media since the rise of algorithms. Misinformation spreads faster than the truth, and our leaders are scrambling to protect our political systems.

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Why Former FDA Commissioner, Scott Gottlieb, Joined the Aetion Board | Carolyn Magil, CEO Aetion


Big news from Aetion CEO, Carolyn Magil, as she talks about the addition of former FDA Commissioner, Scott Gottlieb, to her Board. WHOA. What a HUGE endorsement of support for what Aetion is building…which is what, exactly? Carolyn explains how the company is using real world data (any data outside of clinical trial data) to figure out how different people will react to the same drug. That means they’re using data from health insurance claims, EMRs, wearables, pharma registries, etc. to ultimately save the time, money, and headache of finding out which medicines will work best for which patients. What’s more? A priority for Aetion is helping bring to light how populations usually under-represented in clinical trials (women, seniors, kids) will react to certain treatments. Backed by $77M in funding, and now the former FDA head, tune in to find out what’s next for Aetion.

Filmed at the HIMSS Health 2.0 Conference in Santa Clara, CA in September 2019.

The Untold Reality of Medical Device Shortages in the U.S.

Chaun Powell
Soumi Saha


Say the word “shortage” to a healthcare professional and chances are the first thing that will come to mind is drug shortages. With good reason, too – there are more than 100 drugs currently at risk or not readily available for U.S. hospitals, according to the Food and Drug Administration’s (FDA) drug shortage list. 

Shortages don’t just apply to drugs, however, and as 2019 has shown, healthcare providers must become more focused on shortages of the medical device variety. The shutdown of multiple medical device sterilization facilities in 2019 is poised to jeopardize the availability of devices that are critical to routine patient care. On Nov. 6, the FDA is hosting a panel to hear from stakeholders, including hospital epidemiologists and healthcare supply chain experts, on the risks associated with facility shutdowns and potential action steps.

The industry as a whole is in need of meaningful solutions. As taxpayers, patients and key stakeholders in healthcare, we must collaborate to eliminate interruptions to our healthcare supply chain. For those invested in improving healthcare from the inside, this means working across competitive boundaries and borrowing best practices from sister industries as we work to identify the root cause of these issues and provide meaningful and preventative solutions.

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A Bizarre Claim of Right to Try

Kelly McBride Folkers
Andrew McFayden
Arthur Caplan


A patient with glioblastoma recently received an experimental cancer vaccine at the University of California, Irvine. Notably, this is being hailed as the first case of someone utilizing the Right to Try Act of 2017. ERC-USA, a U.S. subsidiary of the Brussels-based pharmaceutical company Epitopoietic Research Corporation, says it provided its product, Gliovac, to the patient at no cost. The vaccine is currently undergoing Phase II clinical trials. A handful of people in Europe have received access to it through “compassionate use.” This patient did not qualify for ongoing clinical trials in the U.S. The patient, who remains anonymous, is the first known individual to receive an experimental medicine that has not been approved by the FDA, as permitted under the federal right to try law.

Glioblastoma is a nasty cancer – John McCain and Ted Kennedy passed away after battling the disease for just over a year. We believe that patients with terminal illnesses, like those with glioblastoma, should have every reasonable tool at their disposal to treat their disease.

That being said, we’ve argued before that right to try laws are not the best way to help desperate patients. They still aren’t. The number of cases claimed to date is exactly one. And, further examination of what we know about this case does not make a strong argument for the widespread usage of the right to try pathway.

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