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FDA Mandate Initiative Coordinator

The Current FDA Mandate is Not to Maximize Lives Saved

The Food and Drug Administration is responsible for protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices; and by ensuring the safety of our nation’s food supply, cosmetics, and products that emit radiation.

Current FDA Mandate

The FDA Has Effectively Fulfilled Its Mandate

Reducing disease and increasing longevity is not the congressional mandate of the FDA. Its mandate is to ensure the “safety and efficacy of drugs and medical devices”.

The FDA has been very successful at fulfilling its mandate. However, it could completely outlaw the production of any new life-saving treatments whatsoever and it would guarantee that it perfectly fulfilled its mandate. Yet, millions of people would die unnecessarily as a result of the perfect fulfillment of its mandate.

Cost-Benefit Analysis

If you reduce the speed limit to 0 miles per hour, it will be much safer for everyone and you could reduce traffic fatalities by 40k per year. However, there is an economic and societal cost to only moving 0 mph that would exceed the safety benefit.

Likewise, if you dramatically slow the development of life-saving treatments, you will avoid the risk of someone being allowed to try a drug that doesn’t work. However, many people with uncured diseases will die while waiting for treatment.

Safety and efficacy are not inherent goods in themselves. Saving lives and alleviating human suffering are inherent goods in themselves. Hence, these inherent goods should be the focal point and primary objective of the FDA.

Improved FDA Mandate

The Food and Drug Administration is responsible for minimizing the number of deaths and years of suffering experienced by determining the benefits and harms of human and veterinary drugs, biological products, and medical devices; and by determining the benefits and harms of foods, additives, nutritional supplements, cosmetics, and products that emit radiation.

Improved FDA Mandate Focused on Maximizing Inherent Goods

Consistency of Policy and Purpose

It has already been recognized by congress and the FDA that this should be the true goal. This is evidenced by the passage of the Right to Try Act. The act allows those with life threatening diseases to try treatments with uncertain efficacy after all approved treatments have failed.

However, allowing patients access to treatments of unknown efficacy time contrary to the current mandate. Fortunately, congress still passed the law in order to attain the greater good of saving lives. Hence, it is only logical to correct the FDA mandate to extend this goal of the greater good to all FDA policy decisions.

The FEDMI FDA Mandate Initiative Coordinator is responsible for:

  • Develop a detailed study examining the existing Right to Try amendment and the Expanded Access program and outline their shortfalls
  • Assemble a board of expert advisors from patient advocacy groups, government, academia, and industry
  • Work with the board to develop legislation that would expand the existing Right to Try amendment to include anyone suffering from a chronic disease for which no satisfactory existing treatment exists
  • Perform polling to quantify public support for the legislation to be provided to lawmakers
  • Communicate with all 435 members of congress and 100 senators to determine their position on the legislation and determine what changes would be necessary to earn their support

Additional Program Coordinator responsibilities include:

  • Planning and coordination of a program and its activities
  • Ensuring implementation of policies and practices
  • Maintaining budget and tracking expenditures/transactions

Job brief

We are looking for a competent Program Coordinator to undertake a variety of administrative and program management tasks. You will help in planning and organizing programs and activities as well as carry out important operational duties.

To be an excellent program coordinator, you must be organized and detail-oriented, comfortable working with diverse teams. If you have further skills in program development and human resources support, we’d like to meet you.

The goal will be to facilitate the effective management of programs according to the organization’s standards.

Responsibilities

  • Support planning and coordination of a program and its activities
  • Ensure implementation of policies and practices
  • Maintain budget and track expenditures/transactions
  • Manage communications through media relations, social media etc.
  • Help build positive relations within the team and external parties
  • Schedule and organize meetings/events and maintain agenda
  • Ensure technology is used correctly for all operations (video conferencing, presentations etc.)
  • Prepare paperwork and order material
  • Keep updated records and create reports or proposals
  • Support growth and program development

Requirements

  • Proven experience as program coordinator or relevant position
  • Knowledge of program management and development procedures
  • Knowledge of budgeting, bookkeeping, and reporting
  • Tech-savvy, proficient in MS Office
  • Ability to work with diverse and multi-disciplinary teams
  • Excellent time-management and organizational skills
  • Outstanding verbal and written communication skills
  • Detail-oriented and efficient

Operational Guidelines

We are attempting to implement solutions that produce exponential benefits that feedback and accelerate its own progress. That is one of the primary reasons we chose to focus on improving the human mind. Better brains have the ability to find solutions to produce even better brains. This produces a snowball effect of benefits. Not only are better brains inherently good, but they are also better able to find solutions to every other global problem.

Leveraging technology

Hiring an extra researcher is great. However, we could potentially leverage new technology to automate data collection, analysis, and reporting giving us a 1000x increase in speed or 1000x decrease in cost relative to the traditional methodology.

It costs $48k per subject in Phase III clinical trials.  So there’s not a sufficient profit incentive for anyone to do research on the effects of any factor besides a molecule that can be patented. FEDMI supports the Journal of Citizen Science where this research process has been automated.  This system of crowdsourced clinical research has collected over 10 million data points on symptom severity and influencing factors from over 10,000 people. This data has been used to freely publish 90,000 studies on the effects of various treatments and food ingredients on symptom severity.

Positive Feedback Loops

  • Evolution applies positive feedback in that the more capable methods resulting from one stage of evolutionary progress are used to create the next stage.
  • As a result, the rate of progress of an evolutionary process increases exponentially over time. Over time, the “order” of the information embedded in the evolutionary process (i.e., the measure of how well the information fits a purpose, which in evolution is survival) increases.
  • A correlate of the above observation is that the “returns” of an evolutionary process (e.g., the speed, cost-effectiveness, or overall “power” of a process) increase exponentially over time.
  • In another positive feedback loop, as a particular evolutionary process (e.g., computation) becomes more effective (e.g., cost-effective), greater resources are deployed toward the further progress of that process. This results in the second level of exponential growth (i.e., the rate of exponential growth itself grows exponentially).

Positive Feedback Loops and the Brain

Moore’s Law – the scaling property that has seen revolutions in technologies ranging from supercomputers to smart phones – has largely been driven by advances in materials science. As the ability to miniaturize transistors is coming to an end, there is increasing attention on new approaches to computation, including renewed enthusiasm around the potential of neural computation.

Advances in neurotechnologies have revealed neural computation insights into broader computing applications. As we understand more about the brain, we use these discoveries to improve artificial intelligence.

Examples of brain-derived computational techniques include deep learning and neuromorphic hardware. These advancements improve our ability to learn about the brain. and accordingly can be projected to give rise to even further insights.

This positive feedback will produce exponential scaling in computing emerging from our progressive understanding of the brain.

The project coordinator must be able to apply moonshot thinking to the challenge.

Moonshot thinking is when you pick a huge problem and set out to create a radical solution to the problem. To make this happen you have to abandon the idea of creating a 10% improvement. Instead, the focus is a solution that will bring tenfold (or 10x) improvements, or solve it altogether.

1. Huge Problem: Pick a massive problem that, if solved, would positively impact the lives of millions, even billions.

2. Radical Solution: Create and propose a radical new solution to that problem that seems crazy today.

3. Breakthrough Technology: Search for breakthroughs and emerging technologies that exist today and leverage those technologies in your solution. This provides evidence that the solution (though wild-sounding today) may be possible in the future. 

6 Habits of Highly Effective Program Directors

If you do what other successful people do, over and over again, nothing in the world can stop you from eventually getting the same results that they do. And if you don’t, nothing can help you.

So what do successful organizations do differently from unsuccessful ones? In a word, leverage.

Give me a lever long enough and a fulcrum on which to place it, and I shall move the world.

Archimedes
From Forces for Good

The methods of attaining this leverage can be broken down into 6 steps.

1. Serve Individuals and Advocate on Their Behalf

Work with government and advocate for policy change

High-impact organizations don’t just focus on doing one thing well. They may start out providing great programs, but eventually, they realize that they cannot achieve systemic change through service delivery alone. So they add policy advocacy to access government resources or to change legislation, thus expanding their impact.

Other nonprofits start out doing advocacy and later add grassroots programs to supercharge their strategy. Ultimately, all of them bridge the divide between service and advocacy, and become good at doing both. And the more they advocate and serve, the greater the impact they achieve.

We serve directly by helping

– individuals collect data and discover hidden factors increasing their risk or severity of dementia or mental illness.

– companies, organizations, and researchers share anonymous data

We advocate by working with the government to

– provide resources to researchers as well as

– reducing regulations that impede data sharing, experimentation, and scientific progress.

2. Make Markets Work

Harness market forces and see business as a powerful partner

Tapping into the power of self-interest and the laws of economics is far more effective than appealing to pure altruism. Great nonprofits find ways to work with markets and help businesses “do well while doing good.”

Ways of leveraging market forces to achieve social change on a grander scale include:

  • influencing business practices
  • building corporate partnerships
  • developing earned-income ventures such as software development and data analysis services for business

We work with pharmacies, online grocers, and healthcare providers to give individuals access to their health, treatment, and diet data. We also work to provide an option for individuals to easily and anonymously share their data with the aggregated data pool to accelerate research.

3. Inspire Evangelists

Convert individual supporters into evangelists for the cause

Great nonprofits see volunteers as much more than a source of free labor or membership dues. They create meaningful ways to engage individuals in emotional experiences.

Ways We Inspire Evangelists

We reward citizen scientists for their data donations and researchers for publishing studies using this data.

4. Building Non-Profit Networks

Build and nurture nonprofit networks, treating other groups as allies

Ways We Build Non-Profit Networks
Open Source Software

We do this by creating open-source software that can be used by other research organizations to collect data and create studies.

Affiliate Organizations

We also sponsor local affiliate Crowdsourcing Cures Meetup groups. This involved bringing patients, physicians, researchers, data scientists, and programmers together to work on projects to solve challenging medical problems.

We strive for collaboration not competition. Wheel reinvention should be avoided at all costs.

5. Master the Art of Adaptation 

High-impact program directors are exceptionally adaptive, modifying their tactics as needed to increase their success. They respond to changing circumstances with one innovation after another. Mistakes and failures are an inevitable result of experimentation. But unlike ineffective nonprofits, they master the ability to listen, learn, and modify their approach based on external cues — allowing them to sustain their impact and stay relevant.

6. Share Leadership

High-impact program directors share power in order to be a stronger force for good. They distribute leadership throughout their organization and their nonprofit network — empowering others to lead. And they cultivate a strong second-in-command, build enduring teams with long tenure, and develop highly engaged boards in order to have more impact.

How We Implement These Lessons

The motivation for this project

For thousands of years, everything sucked and the average human life expectancy was 28. Then something happened around 1800 and life-expectancy exploded.

Structural Changes Leading to the Health Explosion

Let’s zoom in and see what happened in the last couple of centuries leading to this explosion.

We see on the timeline are two primary groups of factors:

  1. Research Improvements
  2. Incentive Improvements

Research Improvements

Schools of Medicine

An influx of new state-affiliated pharmacy schools in the 1880s and 1890s helped to raise the level of the practice significantly. Many like the University of Wisconsin combined laboratory science with an experiential requirement for graduation. The growth in schools of medicine trained physicians and researchers in the systematic collection of clinical data on the safety and efficacy of treatments. They also served as hubs where new medical discoveries could be shared.

Medical Journals

The advent of journals such as the Journal of the American Medical Association (JAMA) allowed new discoveries could also be widely disseminated.

AMA Drug Certifications

In 1905, the AMA formed its own Council on Pharmacy and Chemistry which levied a fee on manufacturers to evaluate their drugs for quality (ingredient testing) and safety. Drugs accepted by the Council could carry the AMA’s Seal of Acceptance. The AMA’s Chemical Laboratory tested commercial statements about the composition and purity of drugs in their labs. The Council on Pharmacy and Chemistry followed up with safety
evaluations and rudimentary efficacy evaluations designed to eliminate exaggerated or misleading therapeutic claims. The Seal was awarded to drugs that provided symptomatic relief.

Cooperative Investigations

During the 1920s, ’30s, and ’40s medical researchers began to conduct “cooperative investigations”. These were designed to overcome errors attributed to individual observers working in relative isolation. It instead replaced them with standardized evaluations of therapeutic research in hundreds of patients.

Freedom to Try

Therapeutic experimentation did not begin to gain a true foothold in modern medicine until the U.S. legal system stopped equating experimentation with medical malpractice. In 1935, the state of Michigan authorized controlled clinical investigations as a part of medical practice without subjecting the researcher to strict liability (without fault) for any injury so long as the patient consented to the experiment. In particular, the court accepted that experimentation was necessary not just to treat the individual, but also to help medicine progress. “We recognize,” noted the Court, “the fact that if the general practice of medicine and surgery is to progress, there must be a certain amount of experimentation carried on.”

Incentive Improvements

Medical Patent Protections & Mass Production

In the late nineteenth and early twentieth century, interest in clinical objectivity grew, spurred on not only by astounding successes in laboratory science and clinical medicine abroad (e.g. discovery of microbes, pasteurization of milk, development of anthrax and rabies vaccines). International recognition of medical patents contributed to a boom in large-scale industrial pharmaceutical manufacturing led by Bayer and Pfizer. In 1880, patent medicines constituted 28% of marketed drugs. By 1900, however, they represented 72% of drug sales.

The industrial revolution gave way to technologies allowing for mass production and distribution on a global scale. This is vastly more efficient, and profitable than traditional means. These greater profits drove greater investment and thereby greater medical progress in the field.

In the 1800s there was a big problem with snake oil salesmen making false claims about the concoctions they were selling. The original solution was the AMA Council on Pharmacy and Chemistry certification to ethical drug products that met their standards.

1906 – Ingredient Lists and No Lying on Labels

The 1906 Pure Food and Drugs Act empower the Bureau of Chemistry (forerunner of the FDA) to seize adulterated and misbranded products. The law also prohibited “false and misleading” statements on product labels. The law listed eleven so-called “dangerous ingredients” including opium (and its derivatives) and alcohol which, if they were present in the product, had to be listed on the drug label. This listing requirement alone inspired many manufacturers to abandon the use of many “dangerous ingredients” following the passage of the 1906 Act.

1938 – Safety Trial Requirements

The Federal Food, Drug, and Cosmetic (FDC) Act of 1938 is passed by Congress, containing new provisions:

  • Extending control to cosmetics and therapeutic devices.
  • Requiring new drugs to be shown safe before marketing

Manufacturers were required to demonstrate to FDA that they had carried out all reasonably applicable studies to demonstrate safety and that the drug was “safe for use”.

1962 – New Treatment Approvals Cut By 70%

In the late 1950s, the drug thalidomide became available in 46 countries (but not the US) to treat nausea associated with morning sickness during pregnancy.  Unfortunately, the potential side effects were not fully understood.  As a result, thousands of children were born with birth defects, most notably phocomelia (limb malformations).

Fortunately, the existing 1938 FDA safety requirements completely protected Americans from the fate of Europe. However, amid the mass hysteria over the tragedy, the US government felt compelled to look like it was doing something in response.

As effective safety regulations were already in place, the government instead chose to restrict the production of new treatments primarily by requiring extensive additional efficacy testing via the 1962 Kefauver Harris Amendment.

Results of Increased Restrictions

Reduction in New Treatments

The new regulatory clampdown on approvals immediately reduced the production of new treatments by 70%.

Slowed Growth in Lifespan

Over the previous 50 years, rapid advancements in medical science had been producing a 4-year increase in human lifespan every year. This amazingly linear growth rate had followed millennia with a flat human lifespan of around 28 years. Following this new 70% reduction in the pace of medical progress, the growth in human lifespan was immediately cut in half to an increase of 2 years per year.

Diminishing Returns?

You might say “It seems more likely — or as likely — to me that drug development provides diminishing returns to life expectancy.” However, diminishing returns produce a slope of exponential decay. It may be partially responsible, but it’s not going to produce a sudden change in the linear slope of a curve a linear as life expectancy was before and after the FDA.

Additionally, we’re only 3 lifetimes from George Washington. The modern scientific method has only been systematically applied to medicine for like .0001% of human history. However, the more clinical research studies I read, the more I realize we don’t know. We know basically nothing at this point compared to what will eventually be known about the human body. And the currently highly restrictive overly cautious method of clinical research prevents us from knowing more faster. We’re at the very beginning of thousands or millions of years of systematic discovery. So it’s unlikely that this decline in lifespan growth is the result of diminishing returns due to our running out of things to discover.

2 Year Drug Lag

It currently takes over 10 years for a life-saving drug to make its way through the FDA’s regulatory process and become available to dying patients.

Perhaps it’s a coincidence, but you can see an increase in drug approvals in the 80’s and at the same time the gap between Switzerland and the US gets smaller then. Then US approvals go back down in the 90’s and the gap expands again.

Here’s a news story from the Non-Existent Times by No One Ever without a picture of all the people that die from lack of access to life-saving treatments that might have been.

Human Costs of the High Cost of Clinical Research

Since 1962, the cost of bringing a new treatment to market has gone from $74 million to over $1 billion US dollars (2020 inflation-adjusted).

Treatments for Rare Diseases Make No Financial Sense

The costs of FDA regulations do not vary with the number of potential users of the drug, so the decline in drug development has been especially important in the treatment of rare diseases. By definition, each rare disease afflicts only a small number of people, but there are thousands of rare diseases. In aggregate, rare diseases afflict millions of Americans: according to an AMA estimate (AMA 1995), as many as 10 percent of the population. Thus, millions of Americans have few or no therapies available to treat their diseases because of increased costs of drug development brought about by stringent FDA “safety and efficacy” requirements. In response to this problem, in 1983 the Orphan Drug Act was passed to provide tax relief and exclusive privileges to firms developing drugs for diseases affecting two hundred thousand or fewer Americans (AMA 1995). It would be better to reduce or eliminate FDA regulations for all drugs and patient populations.

Oligopolies Protect Existing Inferior Treatments

Prior to 1962, a brilliant scientist could come up with a new treatment, raise $74 million dollars for safety and efficacy testing, and bring it to market. With the current cost of bringing a new treatment to market over a billion dollars, there are only a handful of companies with enough money to risk a billion with a 90% chance of rejection by the FDA. So today the brilliant scientist goes to one of these companies and the company buys the patent for several million dollars. It’s likely the drug company already has an existing inferior drug on the market that they’ve already spent a billion dollars getting approved.

Then the drug company has 2 options:

Option 1: Risk $1 billion on clinical trials

Possibility A: Drug turns out to be one of the 90% the FDA rejects. GIVE BANKER A BILLION DOLLARS. DO NOT PASS GO.

Possibility B: Drug turns out to be one of the 10%, the FDA approves. Yay!!! Now it’s time to try to recover that billion dollars. However, there are very few drug companies with enough money to survive this game. So, this company almost certainly already has an existing crappier drug on the market to treat the same condition. Hence, any profit they make from this drug will likely be subtracted from revenue from existing inferior drugs they’ve already spent a billion dollars on.

Option 2: Put the patent on the shelf

Do not take a 90% chance of wasting a billion dollars on failed trials. Do not risk making your already approved cash-cow drugs obsolete.

What’s the benefit of bringing better treatment to market if you’re just going to lose a billion dollars? Either way, the profit incentive is entirely in favor of just buying better treatments and shelving them.

With the incentives completely stacked against the discovery of new treatments, it’s amazing there’s any medical progress whatsoever. In fact, a complete stoppage in medical progress is exactly what we’ve seen if it’s measured by lifespan.

Efficacy Trials Before 1962

There are hundreds of conditions that a given drug may be effective at treating. However, it’s impossible to know which conditions a drug may improve until it is tried by real-world patients.

Prior to the 1962 regulations, it cost a drug manufacturer an average of $74 million dollars (2020 inflation-adjusted) to develop and test a new drug for safety before bringing it to market. Once the FDA had approved it as safe, efficacy testing was performed by the third-party American Medical Association.

When all other treatments had failed, the 144,000 Physicians in the American Medical Association were allowed to offer suffering or dying patients the option of trying proven-safe treatments for which the effectiveness was not yet known.

The AMA would collect data from its 144,000 physicians members on the efficacy of different drugs for various conditions. Once it was determined which conditions a drug was or was not effective for, the results would be published in the Journal of the American Medical Association (JAMA). The AMA would only give its seal to drugs which it had determined were safe and effective for specific conditions.

The 1962 regulations made these large real-world efficacy trials illegal. Ironically, despite the fact that the new regulations were primarily focused on ensuring that drugs were effective through controlled FDA efficacy trials, they massively reduced the quantity and quality of the efficacy data that was collected for several reasons:

  1. New Trials Were Much Smaller
  2. Were Far More Expensive
  3. Participants Were Less Representative of Actual Patients
  4. They Were Run by Drug Companies with Conflicts of Interest Instead of the 3rd Party AMA

Exclusion Criteria

Subjects in FDA Trials Are Not Representative of the Actual People Receiving Treatment

External validity is the extent to which the results can be generalized to a population of interest. The population of interest is usually defined as the people the intervention is intended to help.

Phase III clinical trials are designed to exclude a vast majority of the population of interest. In other words, the subjects of the drug trials are not representative of the prescribed recipients, once said drugs are approved. One investigation found that only 14.5% of patients with major depressive disorder fulfilled eligibility requirements for enrollment in an antidepressant efficacy trial.

As a result, the results of these trials are not necessarily generalizable to patients matching any of these criteria:

  • Suffer from multiple mental health conditions (e.g. post-traumatic stress disorder, generalized anxiety disorder, bipolar disorder, etc.)
  • Engage in drug or alcohol abuse
  • Suffer from mild depression (Hamilton Rating Scale for Depression (HAM-D) score below the specified minimum)
  • Use other psychotropic medications

These facts call into question the external validity of standard efficacy trials.

Impossible to Discover Effectiveness for All Conditions

The fact that co-morbidities are excluded also makes it impossible to discover potential new uses for a treatment.

Sources

New Trials Were Very Small

Millions of people are prescribed medications based on efficacy trials with as few as 20 participants.

Due to exclusion criteria and added cost, patient sample sizes are very small. The number of subjects per trial on average is:

  • 275 patients are sought per cardiovascular trial
  • 20 patients per cancer trial
  • 70 patients per depression trial
  • 100 per diabetes trial

You can look up the efficacy and trial size for any drug at https://dailymed.nlm.nih.gov. On a drug page, scroll down to the “CLINICAL STUDIES” section to see the efficacy tables. Here’s the data for Immediate-Release Bupropion (Wellbutrin).

Source: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbc8c074-f080-4489-a5ae-207b5fadeba3

Solution: Collect Quantified Self Data on Actual Patients

In the real world, no patient can be excluded. Even people with a history of drug or alcohol abuse, people on multiple medications, and people with multiple conditions must be treated. Only through the crowdsourcing of this research, would physicians have access to the true effectiveness rates and risks for their real world patients.

The results of crowdsourced studies would exhibit complete and utter external validity since the test subjects are identical to the population of interest.

Sources