FDA Drug Approvals: Let Us See All the Evidence

 Approval of a novel drug by the FDA garners worldwide respect. It signals that the safety and efficacy of a medication has been demonstrated in carefully monitored research studies. According to written standards, effectiveness must be demonstrated by substantial evidence. Until relatively recently, "substantial" was defined as at least two well-controlled clinical investigations. However, in 2017 the implementation of the 21st Century Cures Act

opens in a new tab or window relaxed the standardsopens in a new tab or window to make it easier to gain FDA approval on the basis of a single trial.

Over the last several years, I have been working on an independent accounting of evidence used for each new FDA approval in collaboration with colleagues Veronica Irvin, PhD, MPH, at Oregon State University, and Amanda Koong, MS, a McGovern/University of Texas medical student. Earlier this month, we published an analysis

opens in a new tab or window showing that in 2022, a single study was used to justify 65% of novel drugs approvals. In 2016, the year prior to the implementation of the 21st Century Cures Act, a single study was used to justify only 20% of new approvals. In 2016, 55% of the products were approved on the basis of three or more studies. By 2022, three or more studies were used to justify approval of only 11% of novel drugs.

This week, we published another analysisopens in a new tab or window that focused on the 46 FDA approvals in 2017. We choose 2017 because it was the first year the Cures Act was in effect. Using ClinicalTrials.gov, we were able to document how many studies were initiated, completed, and reported before and during the 5 years after each product was approved. We found that in 2017, 41% of the products were approved on the basis of a single trial. When we probed further, it was apparent that other studies had often been initiated before the approval. In many cases these studies had finished data collection many years before. Among studies completed prior to approval, only about one in four had made their results public. Even after 5 years, less than half of the studies had disclosed their results. We also found that companies commonly wait until a drug is approved before releasing results. For 72% of medicines approved in 2017, new information was made public shortly after approval.

We are not the first to report that many completed studies fail to report results. And, we join others who have questioned the level of transparent

opens in a new tab or window reporting. Along with these colleagues, we worry that limited availability of trial results deprive consumers and healthcare providers of the full picture necessary to make good decisions.

Although these issues are hiding in plain sight, attempts to address them have fallen flat. The FDA Amendments Actopens in a new tab or window (FDAAA) includes specific provisions to remedy non-publication of clinical trial results. In particular, the FDAAA allows a fine of up to $10,000 per day (with a ceiling of $1 million) for failure to disclose trial results within a year of study completion. The policy was formally implementedopens in a new tab or window in January 2017. Yet, a 2021 reportopens in a new tab or window revealed that the FDA had never issued a non-compliance notice up to that point. Further, they had never imposed a single fine. Simply enforcing the authority to collect these penalties would have yielded $19 billion in legitimate fines. To put the $19 billion in context, it is about triple the 2022 FDA budget allocation. Further, the 2017 deadline for reporting compliance seems to have had little effect. Our analysis of 2017 approvals showed a greater gap between completed trials and those reporting results than analyses completed prior to 2017opens in a new tab or window.

It might be argued that companies should be allowed to report only their most convincing evidence. In science practice, it is common for labs to present only their most pristine data. In their evaluation, FDA could consider proof of principle rather than considering averages across many studies of varying quality. But focusing on single trials raises important questions. We expect about one trial in 20 to provide a statistically significant result by chance alone. Our concern is that the single study used to establish the safety and efficacy of a particular product could be a false positive result. Putting trial results within the context of all studies that have been completed offers patients and their providers a better basis for making crucial treatment decisions.

We concluded our recent publication with the suggestion that consumers deserve access to all evidence regarding the drugs they might take. It is unfair to limit public disclosure to a subset of selected studies that may show a product in the best light. And, achieving better transparency may be as easy as enforcing existing federal policy.

Robert M. Kaplan, PhD, MA,opens in a new tab or window is a faculty member at Stanford University's Clinical Excellence Research Center, a former associate director of the National Institutes of Health, and a former chief science officer for the Agency for Healthcare Research and Quality.

https://www.medpagetoday.com/opinion/second-opinions/106064

Coercive abortions are at the heart of the FDA abortion pill case

 The Fifth Circuit Court of Appeals ruling on the Food and Drug Administration’s (FDA) approval of the abortion pill was complicated, but it makes several things clearer.

First, mail-order abortion pills are not safe. Second, the FDA likely failed to follow the law in loosening safety standards on these pills. To that I would add this: Mail-order abortion fuels and expands the epidemic of unwanted abortions.

As this case is likely headed to the Supreme Court, I hope all the judges and the public consider what the data say about coerced and unsafe abortion.

My latest peer-reviewed research on this crisis shows that almost 70 percent of women with a history of abortion describe it as coerced, unwanted or contrary to their own preferences and values. In many cases, the pressure to abort escalates into emotional or physical abuse. 

The FDA’s recent approval of mail-order abortions only increases this danger. Now, anyone can obtain and stockpile abortion pills for use against women who refuse to abort voluntarily.  This is no frivolous or merely theoretical concern, as there are already known cases of abortion pills being slipped into pregnant women’s drinks.

Surely it is not the FDA’s intent to directly aid abusers and sex-traffickers. But it is also clear that they are willing to accept this collateral damage in exchange for making access to abortion slightly easier. As the FDA’s lawyer admitted during oral arguments, “No doctor has to be involved.” And that points to what is really driving the FDA’s agenda: a march toward ever faster, cheaper and unlimited access to more abortions.

Why do I accuse the FDA of ignoring the health of individual women in favor of a social policy favoring higher abortion rates than women would freely choose on their own? Because the history of the movement to legalize abortion reveals that it was driven by eugenicists and population controllers. 

Lawrence Lader, co-founder of the National Association for the Repeal of Abortion Laws (NARAL), claimed credit for convincing Betty Friedan and her National Organization of Women to embrace “a woman’s right to control her own body” as a basis for joining in his efforts in support of legalized abortion. While Lader exploited pro-woman rhetoric, in fact, he was a radical population control advocate, more than willing to risk women’s well-being in exchange for lower birth rates.

According to Lader: “In a larger sense, each woman who decides whether or not a fetus should become a child affects the population charts.” Therefore, he argued, increasing abortion rates was essential to reduce the social burden of the “unwanted classes” and the related risk of “the violent rebellion of minority groups.”

Similar motives were revealed in what became a world changing letter from Ron Weddington, now archived in the Clinton Library.  Weddington, who had been co-counsel in Roe v. Wade with his wife, Sarah, captured President Clinton’s attention. Weddington argued that there was an urgent need to “eliminate the barely educated, unhealthy and poor segment of our country” since “26 million food stamp recipients is more than the economy can stand.”

Taking the president into a sly confidence, Weddington wrote: “There, I’ve said it. It’s what we all know is true.” And although he did not intend to “eliminate” them by rounding them up at gunpoint, as he added quickly, he wanted to do so through a massive propaganda effort and direct government involvement to increase abortion rates, especially among the poor.

This was less than 20 years after North Carolina’s eugenics program had forcibly sterilized more than 7,000 people.

The key to Weddington’s plan was to license Roussel-Uclaf’s new abortion pill to a non-profit group, to “eliminate the need for product liability insurance.” Almost immediately, Clinton began negotiations with Roussel-Uclaf to do precisely that. In a parallel effort, as described in a Mother Jones profile, Lawrence Lader and his population control comrades began their own FDA-approved abortion pill testing.

Ultimately, the RU-486 license was given to the Population Council, founded by eugenicists John D. Rockefeller III and Frederick Osborn, a founding member of the American Eugenics Society. During World War II, the word “eugenics” fell into disfavor. The purpose of the Population Council was to advance and rebrand eugenic objectives within the lexicon of population control and to blaze the way toward repeal of abortion laws.

To these ends, Clinton ordered the FDA to bring the abortion pill to market as speedily as possible. The FDA’s accelerated approval process included abridged investigations of both efficacy and safety. Efficacy was not measured by any evidence of improvement of women’s physical, emotional or social well-being, but judged purely on how many abortions were completed without the need for subsequent surgical interventions.

Safety was judged only by immediate physical complications, voluntarily and selectively reported by abortion providers. There was no investigation of any long-term physical risks, much less any consideration of the evidence showing that abortion contributes to negative psychological effects, especially among women pressured to abort.

Nor did the FDA ever require a systematic investigation of mortality rates, even after it was shown that literally all record linkage studies have found an elevated risk of premature death following abortion, including a six-fold increased risk of suicide.

In short, the FDA has stubbornly refused to consider the frequency of unwanted abortions and the harms they cause to women. Even after the 2008 report of the American Psychological Association’s Task Force on Mental Health and Abortion identified 15 risk factors that reliably identify which women will have the most negative reactions to abortion, one of which is “perceived pressure from others” to abort, the FDA failed to require any screening for these risk factors. They are not even mentioned in the pill’s package insert warnings.

Instead, the FDA is happy to embrace the lie that abortions occur only when women freely want them. But the evidence shows that most abortions are pushed on women contrary to their own personal values and preferences.

These facts informed the Alliance for Hippocratic Medicine’s suit against the FDA. These doctors know and treat countless victims of unwanted, unsafe and unnecessary abortions every day. They know that it is largely for ideological reasons that the FDA has turned a blind eye to abortion’s negative effects on individual women.

Women deserve better. I hope the Supreme Court will agree. 

David C. Reardon, director of the Elliot Institute, is an associate scholar at Charlotte Lozier Institute and the author of “Making Abortion Rare: A Healing Strategy for a Divided Nation” and other books and peer-reviewed studies.

https://thehill.com/opinion/healthcare/4169247-coercive-abortions-are-at-the-heart-of-the-fda-abortion-pill-case/

Lee Fang: Nikki Haley's Sudden Wealth Rooted In Weapons Industry, Pro-War Advocacy Network

 by Lee Fang via leefang.com (emphasis ours),

When should America deploy its armaments and forces to conflicts around the globe? And how much of the American military intervention abroad is shaped by genuine humanitarian and U.S. interests versus the tangled web of foreign alliances, special interest groups, and defense contractors?

These questions, which have long divided both major political parties, were on display in Milwaukee last night week at the first Republican presidential debate as foreign policy loomed as a key point of contention. 

Vivek Ramaswamy, as the only candidate directly against any escalation in the Ukraine-Russia war and against any additional U.S. funds, argued that the conflict represented “another no-win war” like the wars in Iraq and Vietnam. The biotech investor favors a quick negotiated end to the fighting and an alliance with Russia to help contain China against any future aggression, as well as a greater focus on domestic issues, such as immigration.

Several candidates, in contrast, bitterly argued that supporting Ukraine is a moralistic necessity.

Mike Pence, a proponent of increased military support to Ukraine, said that Russian President Vladimir Putin “is a dictator and a murderer, and the United States of America needs to stand against authoritarianism.”

Nikki Haley, who also backs more American funds and military support for the conflict, made similar remarks. “Look at what Putin did today. He killed Prigozhin. When I was at the U.N., the Russian ambassador suddenly died. This guy is a murderer,” said Haley.

But the debate turned personal a moment later, as Haley charged that Ramaswamy is “choosing a murderer over a pro-American country.”

"I wish you well on your future career on the boards of Lockheed and Raytheon," Ramaswamy shot back.

“You would make America less safe. You have no foreign policy experience, and it shows,” countered Haley. 

The incendiary exchange, which instantly became a viral, made-for-television exchange clip shared widely, belied a deeper divide in foreign policy and the curious background of Haley, who went from near negligible wealth – with virtually no assets or investments other than a bank account with less than $15,000 in 2017 and up to $1 million in debt – to a sizable fortune.

Over the last year, Haley and her husband reported a vast investment stock portfolio and $12 million of income.

The former South Carolina governor left the Trump administration in 2018 at a time when her parents were struggling financially and had just faced foreclosure. Those days are over. Haley now resides in a 5,700-square-foot mansion on Kiawah Island now worth close to $5 million. Haley and her husband also helped sell a strip mall once owned by her parents and worked to clear the family of previous debts.

Along the way, Haley became wealthy in large part from her ties to a network of defense interests and hawkish advocacy organizations tied to U.S. and Israeli intelligence officials.

In one of her first reported private sector jobs after leaving her last government post, Haley joined the board of Boeing, a defense contractor, a position that paid around $300,000 a year in cash and stock. Haley, according to disclosures, still owns up to $250,000 in Boeing stock.

Haley’s primary income, aside from speaking engagements, is from United Against a Nuclear Iran, an advocacy group shrouded in secrecy.

The group, which has lobbied for military strikes on Iran, is advised by Zohar Palti and Tamir Pardo, two former Israeli intelligence officials, as well as many former U.S. national security officials. The Department of Justice previously intervened in a lawsuit to prevent the disclosure of United Against a Nuclear Iran's donors, claiming that doing so would "cause harm to national security."

Haley also works as a consultant to Prism Global Management, a New York-based investment fund run by Richard Kang, a position that earned $708,335. While the investment fund has no substantial online presence, Kang is active in the defense world and serves as an advisor to America’s Frontier Fund, a new group backed by former Google chief executive Eric Schmidt and run day-to-day by Gilman Louie, the former head of In-Q-Tel, the CIA’s venture capital arm. 

At a launch event for the fund last year, a participant openly discussed the fact that America’s Frontier Fund is investing strategically in “choke points” in case of war between China and Taiwan, in which case the fund’s portfolio would increase “10x, like overnight.”

Michael Haley, Nikki’s husband, also launched his own defense contracting firm in recent years. Michael who previously served with the National Guard, along with stints in human resources and at a high-end clothing store, earns up to $500,000 from a company called Allied Defense.

An investigation from the Daily Beast showed that Allied Defense appears to overlap with a sister company, Defense Engineering Services, that helps clients “navigate political and legal concerns to allow for defense system acquisition."

IKOR Systems, a firm founded by Michael, touts clients in “aerospace manufacturing,” as well as gaming. The website for the company provides few details. But the company brought in up to $1 million in income for the couple.

https://www.zerohedge.com/political/lee-fang-nikki-haleys-sudden-wealth-rooted-weapons-industry-pro-war-advocacy-network

Biden advisers bristle at Gavin Newsom's plan to debate Ron DeSantis

 California Gov. Gavin Newsom is increasingly being viewed as a nuisance to some of President Joe Biden’s political advisers, according to four people familiar with the matter.

Though Biden's camp no longer sees the California governor as a wannabe challenger to the president — and some in the president's orbit praise him for acting as a top campaign surrogate — Newsom’s plan to debate Florida Gov. Ron DeSantis on television carries more risk than potential reward, these people say. 

That's caused consternation within Biden's operation and among Vice President Kamala Harris' allies.

Some Biden advisers have complained privately that the planned debate, which would be moderated by Fox News host Sean Hannity, could make voters think Newsom is running a shadow 2024 campaign at a time when most Democrats say they’d prefer a different candidate at the top of the ticket. They also argue that it could elevate DeSantis, whom White House advisers initially perceived as a greater threat to Biden’s re-election hopes than the GOP front-runner, former President Donald Trump. (Others have insisted that there is no harm in them debating and, in fact, could be a net positive.)

Harris allies take particular umbrage at what they see as Newsom's attempt to position himself for the 2028 Democratic presidential primarily at the expense of the vice president.

"It's disrespectful," said one outside adviser to Harris. "Joe Biden is running with Kamala Harris. That's the Democratic ticket."

It's not clear yet that the debate will actually go forward: the two camps have been haggling over proposed rules since DeSantis accepted Newsom's standing challenge earlier this month. But the specter of the two governors going head to head has highlighted the degree to which Biden interests are not always clear and can diverge from Harris' interests.

Newsom is expected to be a top surrogate for Biden's campaign at the second Republican presidential primary debate in Simi Valley, Calif. in September, according to a Democratic aide familiar with the plans. 

Yet just as some Biden advisers are irked by Newsom's move, others see potential benefit in a high-profile Democrat defending the president's record and agenda against a prominent Republican hopeful.

"What he's doing here is appropriate for a surrogate. It would not be appropriate for the president or the vice president," said one Biden adviser who lauded Newsom for taking on DeSantis and for sharing a donor list with the president's re-election campaign.

"We're in close touch with him," this adviser said. "This is the kind of thing we want surrogates to do."

Newsom did not respond to a text message seeking comment on what he learned about DeSantis from Wednesday's Republican primary debate and whether he thinks the two men will end up debating.

This isn't the first time the White House has had to contemplate whether Biden and Harris are collateral damage in Newsom's efforts to elevate himself.

Last year, Biden advisers closely tracked Newsom's national political activity, concerned that he might be laying the groundwork to run in 2024. He assured then-White House Chief of Staff Ron Klain that he was "not interested" in a 2024 bid, according to a person familiar with the conversation.

With many Democrats looking for an alternative to Biden, who turned 80 in November, some of Newsom's maneuvers into the national spotlight were perceived as promoting the California governor at the cost of stoking concerns about the president.

But in the months since Biden announced his re-election campaign in April, Newsom has become a top surrogate, and most of the president’s advisers have welcomed his help. One set of Biden's advisers are content with a potential Newsom-DeSantis showdown, seeing political upside for the president and the party if DeSantis falters, according to people familiar with the discussions.

On the other hand, a strong DeSantis showing could strengthen him and weaken Democratic arguments. The Florida governor exchanged barbs with Harris earlier this summer as she harshly criticized a state education mandate to teach about the "benefits" of slavery.

She declined DeSantis' entreaty last month to engage with him directly on the issue and then he agreed to debate Newsom. Though the challenge had been issued much earlier, Newsom's decision to move forward came in the shadow of Harris' arm's-length back-and-forth with DeSantis.

While the two governors tussle over the rules and timing of a debate — it could happen this fall, possibly in November — DeSantis is trying to gain traction in his uphill fight to beat Trump for the 2024 GOP nomination. 

DeSantis and Newsom already have sparred over a range of issues, including crime, Covid, abortion rights, education and migrant policy. Newsom has run ads in Florida targeting DeSantis’ positions. 

One Biden adviser bristled at the message the possible debate sends about Harris and about the early jockeying for the party’s 2028 nomination.

“It could either look one of two ways: like he tried to defend her because she couldn’t defend herself or that he was being thirsty for attention or to get in the fight,” the Biden adviser said. “And it was at a time when the VP had completely dismissed and won the fight with DeSantis, and I think Gavin gave him a second life.”

https://www.msn.com/en-us/news/politics/biden-advisers-bristle-at-newsoms-plan-to-debate-desantis/ar-AA1f

Biden staffers met with Special Counsel Jack Smith’s aides before Trump indictment

 The White House counsel’s office met with a top aide to Special Counsel Jack Smith just weeks before he brought charges against former President Trump for allegedly mishandling classified documents — raising serious concerns about coordinated legal efforts aimed at President Biden’s likely opponent in 2024.

Jay Bratt, who joined the special counsel team in November 2022, shortly after it was formed, took a meeting in the White House on March 31, 2023, with Caroline Saba, deputy chief of staff for the White House counsel’s office, White House visitor logs show.

They were joined in the 10 a.m. meeting by Danielle Ray, an FBI agent in the Washington field office.

Nine weeks later, Trump was indicted by Smith’s office on June 8, 2023.

Bratt, 63, also met with Saba at the White House in November 2021, when Trump was mired in negotiations with the National Archives, who were demanding the return of presidential records from his Mar-a-Lago estate before a formal investigation had not yet been opened.

Saba, who is not an attorney, left the White House in May to attend law school.

Special counsel Jack Smith visited the White House during the Trump probe.

Getty Images

Jay Bratt, a top aide to special counsel Jack Smith met with the White House counsel’s office just weeks before Trump was indicted.

DOJ

Bratt had a third meeting in the White House in September 2021, this time with Katherine Reily, an advisor to the White House chief of staff’s office.

The logs offer no information about what was discussed at the meetings.

Critics and legal experts questioned why Bratt was taking meetings at all with the White House counsel’s office while part of an active investigation into President Biden’s likely 2024 Republican opponent.

“There is no legitimate purpose for a line [DOJ] guy to be meeting with the White House except if it’s coordinated by the highest levels,” said former NYC Mayor Rudy Giuliani, a one-time top federal prosecutor in the Southern District.

Caroline Saba, a deputy chief of staff for the White House counsel’s office, met with Jay Bratt at the White House, records show.

Linkedin Caroline S.

When asked if he believed the White House and special counsel were coordinating the prosecution of Trump, Giuliani said: “You’re damn right I do.”

“What’s happening is they have trashed every ethical rule that exists and they have created a state police. It is a Biden state prosecutor and a Biden state police,” he continued.

The former mayor, who represented Trump during special counsel Robert Mueller’s 2018 probe of Russian interference in the 2016 election, was indicted last week in Fulton County, Georgia in connection with attempts to overturn the 2020 presidential election.

George Washington University law professor Jonathan Turley said the March meeting was particularly troublesome and “raises obvious concerns about visits to the White House after [Bratt] began his work with the special counsel.”

The White House meeting raises additional questions.

AFP via Getty Images

“There is no reason why the Justice Department should not be able to confirm whether this meeting was related to the ongoing investigation or concerns some other matter,” he said.

Peter Carr, a spokesman for the special counsel, said Bratt was at the White House for a “case-related interview” but declined to comment further.

The FBI declined to comment.

A person with knowledge of the 2023 visit insisted that it was “an interview of a career official who was also working at the White House during the Trump Administration.”

Rudy Giuliani, a former federal prosecutor, said the meetings suggested impropriety.

AP

The same individual said the 2021 visits were “national security related.”

Bratt, a Harvard-educated attorney, is a longtime Department of Justice hand and has served as chief of its counterintelligence and export control section in the national security division since October 2018.

The section focuses on investigating and prosecuting cases affecting the national security and foreign relations of the United States.

In this capacity, Bratt visited Mar-a-Lago in June 2022 to inspect storage facilities at the property and personally interacted with Trump.

He later became a leading advocate for the unannounced FBI raid of the property in August of that year, the Washington Post reported.

Stanley Woodward, a lawyer for Trump’s valet, Walt Nauta — who has also been charged by the special counsel’s office — accused Bratt in June of trying to coerce his client’s cooperation by floating Woodward’s past application to be a judge.

In a sealed filing obtained by The Guardian, Woodward alleged that Bratt floated his past judicial application to suggest it might be looked at more favorably if his client were to cooperate with the government against Trump.

Bratt is not the only Department of Justice connection to a Trump indictment.

Another longtime Department of Justice official, Matthew Colangelo — freshly hired in December 2022 into the office of Manhattan’s far-left District Attorney Alvin Bragg — also played a critical role in Trump’s indictment in New York City for alleged hush money payments to porn star Stormy Daniels.

https://nypost.com/2023/08/26/biden-staffers-met-with-special-counsel-jack-smiths-aides-before-trump-indictment/

TScan Therapeutics, Inc. are subject to a Lock-Up Agreement Ending on 25-AUG-2023

 Certain Common Stock of TScan Therapeutics, Inc. are subject to a Lock-Up Agreement Ending on 25-AUG-2023. These Common Stock will be under lockup for 91 days starting from 26-MAY-2023 to 25-AUG-2023.

Details:
The Company directors, executive officers and certain of affiliated stockholders have entered into lock-up agreements for a period of 90 days after the date of the prospectus, offer, pledge, sell, contract to sell, sell any option or contract to purchase, purchase any option or contract to sell, grant any option, right or warrant to purchase, lend or otherwise transfer or dispose of, directly or indirectly, any shares of common stock or non-voting common stock or any securities convertible into or exercisable or exchangeable for shares of common stock or non-voting common stock;The lock-up agreements are subject to various exceptions, and directors and executive officers may be released from the lock-up agreements prior to the expiration of the lock-up period at the sole discretion of Morgan Stanley & Co. LLC.

https://www.marketscreener.com/quote/stock/TSCAN-THERAPEUTICS-INC-124803355/news/Certain-Common-Stock-of-TScan-Therapeutics-Inc-are-subject-to-a-Lock-Up-Agreement-Ending-on-25-AUG-44694813/