Thursday, April 18, 2024

Payments to America's Physicians - A Potential Conflict of Interest

A recent Research Letter published in The Journal of the American Medical Association or JAMA provides us with insight regarding the functioning of the American medical system, particularly, the relationship between physicians and Big Pharma.  In the article, the authors examined data from the federal government's Open Payment platform which records payments to physicians from the health care industry, focusing on physicians in specialty practices.  Open Payments was established under the Physician Payments Sunshine Act in August 2013 in an effort to ensure that patients would have the ability to discern whether financial conflicts of interest may influence physicans' prescribing histories.  Data for physicians are available in a searchable database by either physician name or hospital and, over the past two years includes payments to physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists, anesthesiologist assistants and certified nurse midwives. Payments include but are not limited to research, meals, speaking fees, travel, entertainment, education, grants, charitable donations, honoraria and gifts noting that there is an absence of data on certain types of payments like free drug samples..  


For 2022 alone (the latest year for which data is available), industry made 14.11 million payments totalling $12.58 billion US to physicians as shown here:


Going back to the study as a whole, the authors found that between 2013 and 2022, 85,087,744 payments were made by industry to 826,313 of 1,445,944 eligible physicians across 39 specialties with the median payment of $48 per physician.  The highest annual total value was $1.60 billion in 2019 and the lowest was $863.93 million in 2020.  Let's look at some details:


1.) Highest sum of payments by specialty:


- orthopaedic surgeons - $1.36 billion (31,620 recipients)


- neurologists/psychiatrists - $1.32 billion (58,688 recipients)


- cardiologists - $1.29 billion (33,074 recipients)


- hematologists/oncologists - $825.8 million (17,025 recipients)


- general internal medicine - $588.2 million (97,542 recipients) 


Payments were highly skewed with the payments to median physicians ranging from $0 to $2339 compared to $194,933 for the top 0.1 percent of hospitalists and $4,826,944 for the top 0.1 percent of orthopaedic surgeons.


2.) Highest sum of payments by drug:


- Zarelto - $176.34 million


- Elequis - $102.62 million


- Humira - $100.17 million


Other drugs associated with high payments include Invokana, Jardiance, Farxiga, Dupixent, Botox and Keytruda. 


3.) Highest sum of payments by medical device:


- da Vinci Surgical System - $307.52 million


- Mako SmartRobotics - $50.13 million


- CoreValve Evolut - $44.79 million


Other devices with high payments include Natrelle Implants, Impella, Sapien 3 and Arthrex Devices.


During the pandemic, it became quite obvious that many physicians had very close relationships with the medical industry, in particular, the pharmaceutical arm of the business.    It is quite apparent that the health care industry directs payments of various types to physicians to influence their practices and preferences; by directing payments to physicians and other medical professionals, the health care industry is anticipating greater profits.  After all, they aren't making billions of dollars of payments to their customers without expecting a significant return on their "investments".  Unfortunately, these investments have the potential to create conflicts of interest with some physicians potentially making life and death decisions for their patients based on the influence of their benefactors.

Sunday, April 14, 2024

Comparing the Military Strength of Israel and Iran

With outright hostilities between long-term enemies Iran and Israel now in full bloom, I thought that it would be an interesting exercise to compare the military capabilities of both nations.  For the purposes of this posting, I will be using data supplied by Global Firepower.


Let's look at some key military metrics:


1.) Manpower - 


a.) Total Population - Israel - 9,043,387  Iran - 87,590,873


b.) Available Manpower - Israel - 3,798,223  Iran - 49,050,889


c.) Fit-for-Service - Israel - 3,156,142  Iran - 41,167,710


d.) Active Personnel - Israel - 170,000  Iran - 610,000


e.) Reserve Personnel - Israel - 465,000  Iran - 350,000


f.) Annual Military Age - Israel - 126,607  Iran - 1,401,454


When it comes to manpower, Iran is clearly ahead of Israel, particularly when it comes to the number of citizens that are fit-for-service and those who are reaching military age on an annual basis.


2.) Airpower - 


a.) Total Aircraft - Israel - 612  Iran - 551


b.) Fighter Aircraft - Israel - 241 Iran - 186


c.) Dedicated Attack Aircraft - Israel - 39  Iran - 23


d.) Helicopters - Israel - 146  Iran - 129


e.) Attack Helicopters - Israel - 48 Iran - 13


3.) Land Power - 


a.) Tanks - Israel - 1,370 Iran - 1,996


b.) Armoured Vehicles - Israel - 43,407 Iran - 65,765


c.) Self-propelled Artillery - Israel - 650 Iran - 580


d.) Mobil Rocket Projectors - Israel - 150 Iran - 775


4.) Naval Power - 


a.) Fleet Strength - Israel - 67 Iran - 101


b.) Submarines - Israel - 5  Iran - 19


c.) Frigates - Israel - 0  Iran - 7


d.) Corvettes - Israel - 7 Iran - 3


e.) Patrol Vessels - Israel 45 Iran - 21


There is another key aspect of Iran's strength that Israel does not share; its massive oil reserves.  Iran produces 3.45 million barrels of oil per day compared to none for Israel and consumes 1.935 million barrels of oil per day compared to 235,000 barrels per day for Israel.  This leaves Israel vulnerable to fuel shortages should a long-term military operation take place.  Israel does have 12.7 million barrels of oil reserves however this is dwarfed by Iran's 210 billion barrels of oil reserves, putting it in third place in the world.  When it comes to natural gas, Israel is once again dwarfed by Iran which has the second largest natural gas reserves in the world compared to Israel which ranks at number 41 and has the third largest natural gas production in the world compared to Israel which ranks at number 40.  


Iran also has the largest and most diverse missile arsenal in the Middle East many of which are capable of carrying nuclear payloads.  Here is a table showing Iran's missiles that are most likely to be used for conventional strikes against high-value targets or as a nuclear delivery system:


Overall, according to Global Firepower, when all aspects of each nation's economy and military inventory and considered, Israel's military ranks at number 17 out of 145 nations in the world compared to Iran which ranks at number 14.


When comparing the military strength of both nations, we have to keep in mind that the United States is basically an endless supplier of military equipment to Israel through long-term formal agreements thanks to a bought and sold United States Congress whereas Iran relies to a lesser extent on its growing military relationship with Russia and China.  In any case, should all-out hostilities occur, it will be a long and bloody confrontation between two well-armed nations that represent the growing divide in the global post-American hegemonic world.


Saturday, April 13, 2024

Washington's Unsustainable Fiscal Future

The United States Department of the Treasury recently released the 2023 year end version of the Financial Report of the United States which provides decision makers and citizens with a snapshot of the nation's fiscal health.  Needless to say and not overly surprisingly, the situation looks rather dire.  In this posting, I'll provide you with some summary graphics and commentary from the report and let you decide for yourself what the fiscal future of the United States looks like.


The first table outlines Washington's overall fiscal reality noting that the dollar amounts are in billions (i.e. $1000 billion equals $1 trillion):


The budget deficit for fiscal year (FY) 2023 increased by 23.2 percent or $319.7 billion to $1.695 trillion from the previous fiscal year.  Taxes and other revenues decreased by 9.3 percent or $460.3 billion to 4.466 trillion from the previous fiscal year. thanks to a decline in individual income tax and tax withholdings, a decline in corporate income taxes and decreased deposits of earnings for the Federal Reserve due to increased interest rates as you can see on this chart:


Total liabilities excluding Medicare and Social Security shortfalls grew by 9.9 percent or $3.876 trillion on a year-over-year basis, reaching $42.898 trillion.  Here is a chart showing the breakdown of Washington's liabilities:

Again, it is important to remember that this total liability of nearly $43 trillion does not include the shortfall in funding of both Medicare and Social Security which looks like this in the case of Social Security:


It also does not include intergovernmental debt which, when added to the total liabilities of $42.898 trillion would add an additional $7.09 trillion to the total debt as shown here (with a comparison to 2014):



Here is a chart showing the U.S. budget deficit and net operating costs (revenues vs. costs) for the past five fiscal years:


Here is a very sobering chart showing the projected federal spending and receipts out to 2098 observing that the analysis includes no recessionary periods in the future:


The growth in spending on net interest in the debt is frightening to say the least with net interest costs rising to roughly the same level as all other government spending over the next 75 years.

Lastly, here is a chart showing the historical and projected debt-to-GDP levels between 1980 and 2098:



At the end of fiscal 2023, the debt-to-GDP level was approximately 97 percent and, under current fiscal policies and the projections based on assumptions in the report, will reach 531 percent in 2098.  Here is a table showing the 75-year fiscal gap (i.e. how much primary deficits must be reduced or how much primary surpluses must grow over the next 75 years to make fiscal policy sustainable) and how delays will make the spending decreases and tax increases even more painful and time passes:


Let's close with two quotes taken directly from the report:


"The projections in this Financial Report show that current policy is not sustainable."


"The longer policy action to close the fiscal gap is delayed, the larger the post-reform primary surpluses must be to achieve the target debt-to-GDP ration at the end of the 75-year period.  Future generations are harmed by a policy because the higher the primary surpluses are during their lifetimes, the greater is the difference between the taxes they pay and the programmatic spending from which they benefit."


In other words, all that decision makers in Washington are doing today is kicking the federal debt crisis further and further down the road without making the difficult decisions necessary for responsible spending.  No one in bought and sold Congress is willing to do the heavy lifting and force the federal government to live within its means.  As the authors of the report note, Washington's current fiscal reality is nothing more and nothing less than unsustainable.

Thursday, April 4, 2024

Our mRNA Vaccine Future - The Cure-All For Whatever Ails Us

During the pandemic, mRNA vaccine technology took centre stage in the battle against the SARS-CoV-2 vaccine, the first time that the technology was used in anything but relatively small laboratory trials.  Despite the growing evidence that these vaccines were responsible for a significant number and variety of adverse side effects and that they weren't terribly effective at preventing the spread of COVID-19, this would appear to have opened the door to even wider use of mRNA vaccines.


Here is a screen capture from Moderna's clinical trials website recalling that Moderna was the purveyor of the Spikevax COVID mRNA vaccine:


This Phase 1/2 clinical trial will evaluate the safety and efficacy of the company's mRNA-4359 vaccine which is being designed to slow or prevent the growth of solid tumour cancers in adults.  Apparently, preclinical testing in both cell and animal models of cancer provided initial evidence that the mRNA-4359 vaccine had an impact on the immune system which provided the rationale necessary for it to be offered in Phase 1/2 clinical trials.


Participants in the study must:


1.) Be 18 years of age or older


2.) Have confirmed locally advanced or metastatic cancer - Includes: cutaneous melanoma, NSCLC, non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, MSS CRC, basal cell carcinoma, or triple-negative breast cancer - Also includes: confirmed locally advanced or metastatic melanoma or NSCLC who have received previous checkpoint inhibitor therapy


3.) Have experienced disease progression after receiving standard-of-care therapies or be intolerant to standard-of-care treatment


Participants that have active central nervous system tumours or metastases are excluded from the study.


Participants are expected to attend 17 visits to the trial site over three years with a treatment period of approximately 6 months followed by a 90 day safety followup and a two year followup period.  The vaccine will be administered as an intramuscular injection and pembrolizumab will be administered intravenously.  I found it interesting that this Phase 1/2 trial is taking three years to complete (not including a further Phase 3 trial) whereas the trials prior to the rollout of the COVID-19 mRNA vaccines took place in less than a year.


Participants will be assigned to one of three treatment Arms as follows:


1.) Arm 1a

This group will aim to treat adults who have locally advanced or metastatic cancer (cutaneous melanoma, non-small-cell lung carcinoma [NSCLC], non-muscle invasive bladder cancer, head and neck squamous cell carcinoma, microsatellite stable colorectal cancer [MSS CRC], basal cell carcinoma, or triple negative breast cancer) who have previously received treatment for their cancer.

Participants assigned to Arm 1a will receive the investigational treatment.

The goal of Arm 1a is to determine a safe dose of the investigational treatment.

2.) Arm 1b

This group will include adults who have locally advanced or metastatic melanoma or NSCLC who previously received immunotherapy (called checkpoint inhibitor therapy) for their cancer.

Participants assigned to Arm 1b will receive the investigational treatment in combination with pembrolizumab.

The goal of Arm 1b is to determine a safe dose of the investigational treatment in combination with pembrolizumab.

3.) Pharmacodynamic Arm

In addition to the goals of Arm 1b, researchers will also be evaluating how the investigational treatment and pembrolizumab affect the immune system and the cancer in a group called the Pharmacodynamic (PD) Arm. 

Participants enrolled in the PD Arm will receive the investigational treatment and will also be asked to provide additional blood and tissue samples.

Here is the study overview from the U.S. government's Clinical Trials website:

The study is a non-randomized trial meaning that all patients receive the same treatment.  It is also open-label meaning that clinicians and patients know what Arm of treatment that they are receiving unlike blinded trials where patients do not know their course of treatment.  You'll also note that there is no placebo group.


Imperial College in the United Kingdom, home of COVID-19 pandemic modeller Professor Neil Ferguson, author of a flawed report which led directly to the global pandemic lockdown, recently announced the following:


In the United Kingdom, the trial is being run in partnership between Imperial College London and Imperial College Healthcare NHS Trust.  The first patient to receive the mRNA-4359 vaccine was injected in late October 2023

In late March 2024, Modern also announced that it was advancing three of its mRNA vaccines to late-stage clinical trials including vaccines for cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV) and Varicella-Zoster virus (VZV) (i.e shingles).  Among the trials for additional mRNA vaccines, we find the following:


1.) CMV - CMVictory is a pivotal Phase 3 trial evaluating mRNA-1647 against primary CMV infection in women 16 to 40 years of age. The trial is a randomized, observer-blind, placebo-controlled study designed to evaluate the efficacy, safety and immunogenicity of mRNA-1647. The trial is fully enrolled with approximately 7,300 participants from 290 clinical sites globally.


2.) EBV - Moderna's EBV vaccine candidates are designed to tackle multiple EBV-associated conditions, including prevention of IM (mRNA-1189) and MS and post-transplant lymphoproliferative disorder, a subcategory of lymphoma in solid organ transplant patients (mRNA-1195). The Phase 1 trial for mRNA-1189 was designed to test the safety, reactogenicity and immunogenicity of four different dose levels in participants 12 to 30 years of age in the U.S. The randomized, observer-blind, placebo-controlled study showed mRNA-1189 was immunogenic and generally well tolerated across all dose levels. The Company is advancing mRNA-1189 toward a pivotal Phase 3 trial.

The Phase 1 trial for mRNA-1195 was designed to test the safety, reactogenicity and immunogenicity of two drug products at four different dose levels in healthy EBV seropositive participants 18 to 55 years of age in the U.S. The randomized, observer-blind, placebo-controlled study is fully enrolled.


3.) HSV - The first in human, fully enrolled Phase 1/2 trial of mRNA-1608 is designed to test safety and immunogenicity and to establish a proof-of-concept of clinical benefit in adults 18 to 55 years of age with recurrent HSV-2 genital herpes. The randomized 1:1:1:1, observer-blind, controlled study is fully enrolled with 300 participants in the U.S.


4.) VZV - Moderna's VZV vaccine candidate mRNA-1468 has initial data available from a Phase 1/2 trial, which was designed to test safety and immunogenicity in healthy adults 50 years of age and older in the U.S. The randomized 1:1:1:1:1, observer-blind, active-controlled study of mRNA-1468 elicited strong antigen-specific T cell responses at one month after the second dose and was generally well tolerated. Results of the first interim analysis support the further clinical development of mRNA-1468 for the prevention of shingles. Additional results from the ongoing Phase 1/2 study will be available later this year, including persistence data. The Company is planning for a pivotal Phase 3 trial.


Modern is also awaiting regulatory approvals for mRNA-1345, the company's Respiratory Syncytial Virus (RSV) vaccine candidate which is currently undergoing at Phase 2/3 randomized, observer-blind, placebo-controlled, case-driven trial.


Looking at human illness through the Moderna lens, one can see that the mRNA vaccine experiment on humanity will continue unabated.  Moderna would have us believe that this newly commerciallized technology is the solution to whatever ails us and seems quite capable of ignoring the long list of potential adverse health effects of this technology that are being observed by clinicians and physicians around the world.  Nonetheless, it's full speed ahead when it comes to mRNA technology.