Crisis is Opportunity

On the doorstep of a fifth-generation warfare civil war. #PsyWar Civil War.

Doctor, my eyes have seen the years
And the slow parade of fears without crying
Now I want to understand
I have done all that I could
To see the evil and the good without hiding
You must help me if you can

Jackson Browne, 1972

We are now in a fifth-generation warfare civil war, which has been building up to this point for quite a while now. Whether or not you are aware of this is irrelevant.

The territory being fought over is your mind.

This is now rising to the level of becoming a crisis. However, coexisting with every crisis, there are opportunities for those willing and able to see.

Those who lost the election in the popular vote and electoral college now actively seek to overturn and obstruct the will of the electorate through nefarious means. For example, House Democrats are denying the results of the 2024 election. They are trying to form a "shadow government" to defy and undermine President Trump's authority. The Democratic Party and their surrogates in corporate media are trying to lead an unconstitutional "insurrection" against President Trump.

The other day, I was on a Zoom teleconference with the International Crisis Summit team, conferring with representatives from the Philippines and Canada, and having to field questions from my colleagues concerning the Trump transition team appointments, the responses to those appointments, and the prospects of Senate confirmation. As I tried to explain what is going on, and in so doing tried to see the situation through their eyes, I suddenly realized that we are in the midst of a second Civil War. Only it is not a kinetic war. It is an information war. A Fifth Generation Warfare-based Civil War, to be technically precise.

For those who are not fully tuned into this aspect of the politics of the US federal republic system as defined in the US Constitution, the US Senate is a part of the elected federal government (legislative branch, together with the House of Representatives) that is separate from the other two; the executive branch and the judicial branch. Donald Trump has just been elected as the next US President, heading up the executive branch. For the most part, the executive branch is where the bureaucracy resides.

Senate Consent to Presidential Appointments

According to Article II, Section 2, Clause 2 of the United States Constitution, the President has the power to nominate federal officers, subject to the Senate’s consent. This provision ensures a system of checks and balances between the executive and legislative branches.

• The President nominates federal officers, including Ambassadors, public Ministers and Consuls, Judges of the Supreme Court, and all other Officers of the United States.

• The Senate provides “advice and consent” on these nominations, which has been interpreted as allowing it to reject or confirm the President’s choices.

• The Constitution does not grant Congress the power to exercise the appointment power directly; instead, it limits Congress’s role to advising and consenting on the President’s nominations.

The Framers aimed to prevent tyranny by dividing the appointment power between the President and the Senate. Alexander Hamilton, in Federalist No. 77, warned against a Senate conclave where cabal and intrigue would prevail, and instead advocated for a system of accountability through public confirmation.

The Appointments Clause serves as a restraint on Congress, preventing it from exercising the appointment power or circumventing the President’s authority. The Supreme Court has consistently upheld this provision, rejecting attempts by Congress to make direct appointments or create devices to bypass the President’s role.

To enable political management and guidance of the bureaucracy, the President has a relatively small number of politically appointed associates. The US Constitution states that the US Senate has the right and duty to advise and consent to those appointments, as it also has the responsibility to advise and consent to treaties which the executive branch may enter into. In the case of the Presidential appointments, this “advice and consent” role has evolved into a lengthy vetting process in which Senators are actively lobbied by citizens, press, and corporate representatives (“Lobbyists”) to either agree to or attempt to block presidential appointments. In the case of international treaties, the Senate rarely exercises its rights and responsibilities. But with Presidential appointments, the system has developed into high art Kabuki theater in which appointees are typically subjected to a variety of character assassination attacks by opposed Senators (and their surrogates) designed to deny their appointment, frustrate the President and his ability to achieve his objectives, and degrade the reputations, potential effectiveness as leaders, and prospects for “confirmation” to the appointed position. The elected position of “Senator” has been substantially decoupled from the intended purpose of representing the interests of the individual state governments that they nominally represent consequent to an amendment to the US Constitution (17th amendment). The result has been that the US Senate members now represent their own political interests rather than those of the State Government they previously represented. And so now the “advice and consent” clause has devolved into a political game that is readily manipulated by organizations that exert pressure (or confer favors) upon Senators.

In the current context of the incoming Trump administration, at this point, we have congresspersons seeking to develop a set of “shadow” opposing appointments (a “Shadow Cabinet”), and a feeding frenzy has developed populated by corporate lobbyists and political opponents representing the interests of parties and political groups that the voters rejected, but who seek to use this “advice and consent” process to block the ability of the incoming President to appoint his executive team - his “cabinet,” and those that will serve to guide the established permanent bureaucracy.

The way that these opposition forces are now acting to prevent Trump from being able to rely on those whom he has chosen is to spread disinformation (politically motivated misinformation) about his cabinet picks, to get surrogates to spread disinformation, and to besmirch, spread propaganda, slander and defame the candidate officers, in an attempt to delegitimize them and degrade public support for them. In other words, to engage in fifth-generation warfare skirmishes to deny the elected incoming President his chosen staff.

The outgoing US ambassador to Australia, Caroline Kennedy, has labelled her cousin Robert F Kennedy Jr’s views on vaccines “dangerous”.

After a speech to the National Press Club in Canberra, Australia on Monday, Caroline Kennedy took aim at a number of Trump administration appointees including Tulsi Gabbard, warning that her appointment would “obviously … be of great concern”.

Donald Trump has nominated RFK Jr to oversee US health agencies, despite his propagation of anti-vaccine conspiracy theories, and Gabbard to be director of national intelligence, despite her being a vocal supporter of Russia.

Caroline Kennedy told reporters that as an ambassador, she’s “not supposed to comment on politics and now you’re asking me to also comment on family”.

“But, yes, I think Bobby Kennedy’s views on vaccines are dangerous … but I don’t think that most Americans share them. So we’ll just have to wait and see what happens.

“But certainly he’s – you know, I grew up with him. So, I have known all this for a long time and others are just getting to know him.”

She noted her uncle Ted Kennedy “spent 50 years fighting for affordable healthcare in the Senate”, work that the former president Barack Obama built on with the Affordable Care Act.

“My Aunt Eunice started the Special Olympics and the national institute of maternal and child health is now named after her.

“So I would say that our family is united in terms of our support for the public health sector and infrastructure and has the greatest admiration for the medical profession in our country, and Bobby Kennedy has got a different set of views.”

Asked about Gabbard – a vocal supporter of Russia who Democratic lawmakers have said “poses a threat to US national intelligence” – and whether Australia should trust the US with sensitive intelligence, Caroline Kennedy replied that “there are thousands of people who work in our intelligence agencies and work closely with Australia and we have no more trusted or capable ally and that’s going to continue”.

“So let’s see what happens with President Trump’s appointments. They have been … making waves, headlines … let’s just calm down and wait and see what happens.

“But obviously that would be of great concern and we’ll see who … actually gets confirmed.”

Doctor, my eyes
Tell me what is wrong
Was I unwise to leave them open for so long?

Jackson Browne, 1972

Prior to the election, there were more Republicans (49) than Democrats (47) in the U.S. Senate. But Democrats held majority control since three independent senators — Bernie Sanders of Vermont, Angus King of Maine and Joe Manchin of West Virginia — caucused with the Democrats. A fourth independent, out-going Sen. Krysten Sinema, was elected as a Democrat before breaking away in late 2022.

Therefore, Sen. Charles Schumer was the majority leader and Sen. Mitch McConnell was the Republican leader. This will change to outright Republican party control consequent to the election of 2024. Whether the incoming Senate will permit President Trump to select his own cabinet and leadership has yet to be determined, and an active campaign to deny those choices and frustrate his ability to achieve the goals for which he was elected has officially begun.

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Yesterday, late in the day, Jill and I published a set of recommendations for reforming what has clearly become a deeply dysfunctional US Food and Drug Administration. The scope was broad, and the proposals bold. But nothing in that document was retaliatory. In the context of the COVIDcrisis and mRNA vaccines, I was personally directly lied to by the current director of the FDA Center for Biologics Evaluation and Research, Dr. Peter Marks. CBER and its advisory groups were directly responsible for approving gene therapy products masquerading as vaccines that have damaged large numbers of people, including me, despite repeated assurances that these products were “safe and effective.” Many have lost their lives consequent to accepting these experimental EUA products that were provided not only without adequate informed consent, but with active blocking and suppression of informed consent. However, in developing our recommendations, we focused on corrective actions, not on retribution. The proposal was bold, far-reaching, forward-looking, and professional.

This morning, in response to that substack essay, I received an email from a former FDA colleague. He is a traditional Democrat, and had been quite upset with me when I first appeared on Tucker Carlson’s Fox News broadcast- speaking about the problems with the databases being used to detect and assess adverse events associated with the mRNA vaccines. I believe that was the first time the topic had been addressed publicly, and Tucker was a bit taken aback.

My colleague wrote the following (redacted to protect identity);

Although to be honest I am not happy about the results of the election but I do think it can represent a real opportunity to bring about the reform of the FDA that is urgently needed.  It is good to see you involved in it and hopefully you are on the short list for some sort of leadership at FDA.  I think the agency is in a large part dysfunctional some of it is due to the way information is submitted to the agency and organized once submitted.  Alot of  it is  a management structure that makes it nearly impossible for any real innovation to occur.  

 There are so many redundant and dysfunctional systems at FDA.  I agree that FAERS and VAERS should certainly be combined and there are even additional systems such as CAERS (cosmetics) and MAUDE (devices) from CFSAN and CDRH that could also be readily combined.  There are many other systems at FDA that need to be combined or eliminated.     FDA needs real time access to real world evidence and that is something that is really not available.  Sentinel which the FDA has spent billions on did not give us any real data on the vaccines as you well know.  FDA spends somewhere north of 1 billion dollars a year on IT and it could be substantially reduced and have much better results.  I think what we did the GSRS which is an open source system developed by NCATS and FDA and is being used  by regulators and even industry is a way to go to organize the information that is essential for regulation.  Without organized  information it will be  much more difficult and perhaps even dangerous to rely on AI.  I think the appointment of RFK Jr may be a real opportunity to bring about reform at FDA that is long overdue.  Let me know if there is anything I can do to help.

My point in sharing this is that there are many good people in the FDA bureaucracy who have become quite frustrated with the way things are, and (if approached openly and professionally) are willing to work “across the aisle” to enable reforms. And, if approached professionally, we can reasonably anticipate that they will cooperate to enable both an opportunity for constructive problem solving and innovation, and to advance the overall interests of the citizens of the United States.

The good news about crises is that, if appropriately managed, they can be used to build, empower, motivate, and enable diverse specialist teams to cooperate in solving complicated problems. There is another way to think about the saying “never let a good crisis go to waste”- crises also create opportunities for constructive change, innovation, and problem-solving. A good leader can use a crisis to motivate and build cohesion, particularly when a group is otherwise fragmented or divided against itself. Nothing builds cohesion, motivation, and a sense of purpose better than an external threat. Currently, both sides are frustrated by the sheer weight of bureaucratic inefficiency and incompetence. And within this frustration and sense of crisis lies hidden opportunity.

'Cause I have wandered through this world
And as each moment has unfurled
I've been waiting to awaken from these dreams
People go just where they will
I never noticed them until I got this feeling
That it's later than it seems

Jackson Browne, 1972

The US government and administrative state face multiple internal and external threats. The greatest of those is the federal deficit and debt, resulting from decades of mismanagement by both political parties. Without resorting to hysterics, the blame game, personal attacks, or the infinite range of psychological warfare weapons now available, we should be able to put aside our differences and unify around this common enemy. Now is the time for the grownups to step up and set an example of professionalism and to focus on the task at hand. We don’t need a Civil War. We don’t need more war, let alone WW III. And we don’t need temper tantrums from those who could not convince a majority of the American public of the merit of their plans, perspectives, and arguments.

We need to be civil to each other. For if we don’t hang together, we shall certainly hang separately.

Doctor, my eyes
Tell me what you see
I hear their cries
Just say if it's too late for me

Jackson Browne, 1972

Ukraine has fired US-supplied longer-range missiles at Russian territory for the first time, the Russian government said, a day after Washington gave its permission for such attacks.

US officials also confirmed use of the Army Tactical Missile System (Atacms) to CBS news, the BBC's US partner. Ukraine has not commented.

Russia's defence ministry said the strike had targeted the Bryansk region bordering Ukraine to the north on Tuesday morning.

It said five missiles had been shot down and one had caused damage - with its fragments starting a fire at a military facility.

But two US officials said initial indications suggested Russia had intercepted just two missiles out of around eight fired by Ukraine.

The BBC has not been able to independently verify the contradicting figures.

Russia’s Foreign Minister, Sergei Lavrov, accused Washington of trying to escalate the conflict.

"That Atacms was used repeatedly overnight against Bryansk Region is of course a signal that they [the US] want escalation," he said.

"And without the Americans, use of these high-tech missiles, as [Russian President Vladimir] Putin has said many times, is impossible."

He said Russia would "proceed from the understanding" that the missiles were operated by "American military experts".

"We will be taking this as a renewed face of the Western war against Russia and we will react accordingly," he told a press conference at the G20 in Rio de Janeiro.

Doctor, my eyes
Cannot see the sky
Is this the prize
For having learned how not to cry?

Jackson Browne, 1972

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The following is a summary of additional FDA database and analysis reforms and actions that my colleague has recommended, in addition to those that we previously summarized and proposed :

The GSRS is an open-source tool designed to send structured information on substances and products into FDA. For well over a decade, my Health Informatics colleagues and I have worked to standardize the format and the input of interoperable and fully shareable, and traceable drug substances and products descriptions; bring more traceable control to the global medicinal product supply chain; standardize in-vitro pharmacology data ; and, perhaps, enhance the quality, and availability of medicines in the USA and worldwide.

The primary tool we developed is the Global Substance Registration System (GSRS), created in collaboration with the National Center for Advancing Translational Science (NCATS), which has provided great value to both organizations. The concept behind GSRS was to develop open-source tools that could be distributed to industry and regulatory agencies to send structured information into FDA on both substances and products. The GSRS not only defines substances but tries to integrate data linked to substances products, impurities, and the manufacturing of substances in great detail--and recently an in-vitro pharmacology module to capture the data on which activity, safety and potential drug interactions are based to inform the inclusion and exclusion criteria of clinical trials.

There are initiatives in CDER, including Integrity and KASA systems that structure information essential to regulatory operations, and they use the GSRS extensively. But the main problem with these initiatives is that they involve costly re-entering of data and often don’t reach the level of granularity that is really needed for regulatory action. We spend tens of millions of dollars every year on contractors reentering data into Integrity. We could have gotten the data at no cost using SPL or the GSRS.

I’ve spoken with reviewers using KASA some of whom are stressed because of the time demands of cutting and pasting manufacturing and specification information from applications into KASA. The Integrity and KASA systems were also developed with proprietary software, so they can’t be readily distributed to other regulators or industry to facilitate the exchange and organization of this information.

In the current process a lot of data is structured at pharma and then most of it becomes unstructured when submitted to FDA in the electronic Common Technical Document (eCTD). The eCTD is a good general table of contents but much of the data loses its value when incorporated into PDFs. Efforts have been underway for many years to structure some of the PQ/CMC data but nothing has been implemented. It has relied mostly on ICH efforts which are costly, time consuming and often futile or developing HL-7 messages that are insufficient due to the lack of subject matter expertise and rarely get implemented. Currently, FDA has at least three independent approaches to organize this data and there are several other efforts within the industry.

In the GSRS project we also do a lot of re-entry of substance data that could be readily obtained from industry and at less cost.

CDER could encourage industry to use the GSRS to submit both product and substance data in a structured, pre-defined, acceptable format. The availability and integration of high-quality structured data is essential for many regulatory, data analytic and decision efforts.

Proposing a more effective approach to organize and analyze data

A different approach would be to develop and implement a common, interoperable data model having an ‘as date’ versions control system that could be used by regulators and industry and an open-source for API-driven systems to implement interoperable and sharable data models.

It is essential to align business processes with pertinent and supporting data systems; oftentimes we only think about the internal processes within FDA. However, the processes really begin outside FDA and if the data is not aligned coming in it’s much more difficult and expensive to align it within FDA. Data is not that hard to integrate if you settle on elements that are essential for integration, such as substances and business entities.

We appreciate the support that CDER provided to develop the GSRS and the data within it. The system could not have been built without it. Unfortunately, CDER has never used the GSRS to the extent it could have. Hopefully, the approaches we began in the GSRS will be advanced and CDER will work for agency-wide resources.

Below are some recommendations that really go beyond CDER, based on work done at FDA and United States Pharmacoipe (USP), much of which I’m sure you’ve heard before but hopefully CDER can lead the way to implementation of some of these suggestions:

• An FDA-wide product database that captures every lot of a product--all the ingredients in products we regulate down to the manufacturer and lot of each ingredient. This would facilitate recalls and testing and help tackle shortages. Medicinal products within CDER and CBER should be the first to focus on.

• A single application database for CDER, CBER, CVM, the variety of Food/Dietary databases and CDRH to a certain extent. The Office of Digital Transformation (ODT) is aware of the redundancy of databases/systems in the centers, but it has been difficult to have agency-wide solutions.

• Pre-registration of all medicinal product lots that will be put on the US market with expiry date and ideally lot size. Vaccines does this based on historical lot release testing. (Germany uses something like this to tickle companies within six months of expiry to determine if they are going to produce another lot to address potential shortages).

• Support Global Product and Lot registration. This could help considerably in mitigating shortages, coordinating quality testing and identification of substandard and counterfeit products. (The airline industry has something very similar to this for planes and parts presented this to the legislative group before Covid. It was suggested to go through ICH. For the development of data standards and many other efforts, ICH is perhaps the wrong approach because it takes far too long and even when ICH agrees on a standard such as the HL7 V3 standard for Individual Case Safety Reports (ICSR) the standard is out of date by the time of an attempt to implement. FDA should really lead the way on standards and processes by implementing first with with industry and bring the rest of the world along.

• Encourage the development of USP monographs for all medical products from launch. The lack of monographs limits the testing of materials by non-specialized or non-company labs. It’s particularly disturbing for high-value medicines that are often subject to counterfeiting. The monographs should cover both identity and assays for potency. Impurities could also be covered as well. This would allow state labs and other outside labs to test drug substance and products and facilitate the recall of products based on mislabeling or counterfeiting. Unfortunately, the products in most need of monographs (biologics) don’t have them. For example: Standards are particularly essential for many biologics and complex substances to set a common unitage and to ensure that products maintain unitage up to the point of administration.

• Encourage more transparency and coordination in clinical trials. Somewhere between 80-90% of new molecular entities entering phase 1 trials do not get approved. There have been several severe safety incidents in phase 1 trials where the same drug or a drug against the same target resulted in disability or death. Since the actual substance and the results of the trials were not in any public database, patients were needlessly harmed. If there are any serious safety issues during a trial anywhere in the world the substance, metabolites, and targets should be revealed. Often the active substance that was tested is not revealed to the public or even the FDA if the trial is done overseas. The lack of transparency both before and after a clinical trial means that society does not benefit, which is one of the tenets of both the Declaration of Helsinki and the Nuremberg Code.

• The preclinical data on which the study was based is often not revealed and the extent of preclinical data submitted varies widely. It is very difficult if not impossible for a patient to really give informed consent and the patient often suffers when a trial fails. Making preclinical data and the physician’s brochure public before the beginning of a trial would allow critique from other scientists and physicians hopefully resulting in better trials.

• Encourage more standardization and data standards for the description of all the components, in-vitro assays and laboratory tests. In-vitro assays will become much more important as FDA moves away from animal assays and since they use human targets, cells and tissues can have results that are more relevant to human use. When a drug fails due to toxicity there should always be an assay like the HERG assay that predicts QT

• Shield is attempting to standardize and harmonize the lab test results for the same analytes across instruments and laboratories. The discrepant that results from unstandardized tests and data are being used in the analysis of clinical trials and Real World Evidence.

Clinical Trials

• There is also a strong need to coordinate clinical trials. Covid illustrated the problem with unfettered trials, with over 80% of them either failing or failing to produce any meaningful data. Many non-commercial (research) trials and treatments for initial new drug applications (INDs) never submit results to FDA. Many of these INDs involve off-label treatment regimens with approved drugs. It is essential to collect and make data available on off-label uses for both safety and efficacy or indicate the lack thereof.

• More involvement of actual users in developing tools to assist review. Several tools have been created for reviewers but except for KASA, they’ve had very little input in these tools’ development and have been forced to use ones they find unproductive. The levels of hierarchy make it very difficult for this type of information to travel upward and senior and middle management often make decisions about things they have limited knowledge of or expertise.

There are far too many layers of management at FDA. This has resulted in incessant unproductive meetings, and a dysfunctional and arrogant agency. Innovation is often stifled and alternative opinions often based on science are never taken into account.

• Drug labels need to be standardized, living, and owned by FDA.. The information in drug labels is not standardized and often outdated. Although new drug labels often list interactions with older drugs, the older drug labels say nothing about interactions with newer drugs. There are expert systems used in pharmacies that often pick up the problems when old drugs are prescribed but many of them throw so many warnings that they get ignored. Off-label use can sometimes be very effective or deadly but FDA provides little guidance and essentially ignores it. FDA should provide a repository of data on off-label use or include a section on it in the living labels.

Medication errors

• The number of medication errors and medication-related adverse events increase every year. Polypharmacy is often deadly and responsible for many visits to emergency rooms. I’ve had several friends with cancer who died recently from the treatment and not the disease which is very common. FDA is not responsible for the practice of medicine but can influence it, butreally should do more. I know there are efforts for more appropriate dosing particularly in cancer that hopefully can move forward at a rapid pace.

Adverse events

• Reviewers who look at the adverse events every day feel many of them should be learning lessons and not just statistics, but it is difficult to bring these messages forward.FDA only has passive systems for detecting adverse events. No direct access exists to large sets of medical data to probe for adverse events or efficacy of off-label use. A colleague and I, early on during Covid were able to get access to deidentified real-time claims data from Blue Cross either before or while the EUA [spell out] for hydroxychloroquine was granted. This data showed that it was very unlikely that hydroxychloroquine would have a positive effect on Covid <RWM - this most likely was late-stage Covid, when HCQ would have been ineffective>. The insurance industry did offer us real-time access to this data, but it was rejected by senior leadership. FDA should have constant access to this type of data to respond to emergencies and to monitor the safety or efficacy of medications.

• Sentinel has not proven useful for these tasks because of the lack of direct access and the overall disorganization of health data.

• I would strongly suggest ceasing reliance on consultants’ advice to FDA on how to organize data. Over the past 15 years I have seen FDA bring in costly consultants who proposed things that FDA staff could have done directly if given resources and direct access to developers. The success of the GSRS and KASA is largely due to the systems being developed from a bottom-up approach and not consultant- or contractor-driven.

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