Vaccine Makers Keep Safety Details Quiet, Shocking Scientists

The morning after the world revealed that a clinical clinical trial of a coronovirus vaccine had been halted last week in view of safety concerns, the company’s chief executive revealed that the person giving the vaccine had experienced severe neurological symptoms.

But the comment was not public. Instead, the Chief Executive Officer, Pascal Sorot of AstraZeneca, spoke at a closed meeting organized by investment bank JP Morgan.

AstraZeneca said on Saturday that an external panel had approved its trial to resume testing in the UK, but the company still has not provided any details about the patient’s medical condition, nor has it given investors Has released a transcript of Mr. Soriot’s remarks, which was reported by the news outlet STAT and later confirmed by an analyst for JP Morgan.

Pfizer, another pioneer in the vaccine race, made a similar announcement on Saturday: The company is proposing to expand its clinical trial to include thousands more participants, but it has revealed a few others about its plan Given details, which will determine how involved. The effectiveness of the vaccine is in its larger study.

It is standard for pharmaceutical companies to withhold details of clinical trials until they fully protect their intellectual property and competitive edge. But these are extraordinary times, and now there is a growing resentment among independent scientists and public health experts who are pushing companies to be more open to the public in the midst of an epidemic that already has more than 193,000 in the United States Have killed people. States of America

These experts say that American taxpayers are entitled to find out more because the federal government has paid billions of dollars for vaccine research and to buy the vaccine once they are approved. More transparency can help strengthen public confidence in vaccines at a time when increasing numbers of Americans will pressure federal regulators to get a vaccine before President Trump proves safe and effective.

Yale University cardiologist and health care researcher Dr. Yale University in New Haven, Conn. “Trust is in short supply,” said Harlan Krumolz, who has spent years lobbying companies and educational researchers to share more test data with outside scientists. “And the more they can share, the better we are.”

Last week, nine pharmaceutical companies, including AstraZeneca and Pfizer, promised to “stand with the science” and strictly extended any vaccine for coronovirus – an unusual agreement among competitors. But the researchers said the disappearance from the joint statement was a promise to share more important details about their research with the public and the scientific community.

None of the three companies with coronavirus virus vaccines in advanced clinical trials in the United States has created protocols and statistical analysis plans for those tests – detailed road maps that help independent scientists better understand How the tests were designed, and hold companies accountable if they deviate from their plans. In some cases, important details about how the tests have been set up – such as at what point an independent board can review the results of the initial study, or under which circumstances the test can be stopped early – are not made public. has gone.

“We have such an important clinical trial – or series of clinical trials – in recent history,” Dr. Said Eric Topol, a professor of molecular medicine at Scripps Research in La Jolla, California, and a longtime expert on diagnostics. Tests. “Everything should be transparent.”

The public’s confidence in the pharmaceutical companies’ findings and the rigor of federal regulators will be important in persuading Americans to vaccinate. Increasing numbers of people are suspected. A survey by the Kaiser Family Foundation last week found that nearly two-thirds of Americans – 62 percent – are concerned that the Food and Drug Administration will hurry to approve a coronavirus vaccine to ensure it is safe and under political pressure Be effective. Mr. Trump

Pharmaceutical companies are relying on their vaccine research to help tarnish the industry’s role in driving up drug prices and ending the opioid epidemic.

In an effort to restore public confidence, senior regulators at the FDA released a plethora of ad-eds in the USA Today session on Thursday to maintain the scientific integrity of the treatment and vaccine evaluation process and to maintain the agency’s independence. Took unusual step. .

Representatives of three companies – Modern, Pfizer and AstraZeneca – with vaccine candidates in large, advanced tests in the United States said they had released several details about the tests.

Pfizer said in a statement that the novelty of the virus and the rapidly growing nature of the coronovirus crisis meant that the protocol had to be flexible “to enable us to increase the evaluation of the safety and efficacy of potential vaccines.” The company said it would publish the full protocol from the lawsuit and it would be presented in the medical journal, which would include “the results, enrollment criteria and the final number of enrolled participants.”

On Saturday, Pfizer said it would seek permission from the FDA to expand its testing to 44,000 participants, with an initial target of 30,000. But the announcement raised new questions as to how the company would be able to achieve its target by the end of October with so many new participants. A Pfizer spokesperson, Amy Rose, said, “We are not going to talk about the timing or nuances of any inter analysis.”

AstraZeneca did not initially state that a participant’s illness had halted her clinical trials worldwide. The studies were halted last Sunday, but were not reported by the STAT until the news broke on Tuesday. The company still did not disclose the patient’s illness that led to the stagnation, even though it discussed the medical condition of another participant who developed multiple sclerosis in July, which led to another brief halt of testing. Vaccination of that disease was determined to be unrelated.

The company said that Mr. Soriot’s presence at the JP Morgan meeting was part of a long-planned schedule, and he discussed the company’s business outlook with some questions about the trial. The New York Times reports that the patient has developed symptoms consistent with transverse myelitis, or spinal cord inflammation.

A spokesperson for AstraZeneca, Michel Meisel, said that when an “unexplained event” occurred, test sponsors were required to notify doctors at clinical trial sites, “It is not common for people who are clinical Communicate beyond the community. Trials – including the media – to protect the privacy of individual participants and maintain the integrity of the trial. “

There is precedent for greater transparency. Large recovery trials conducted by the University of Oxford in the UK – which helped determine whether steroids dexamethasone reduces death in patients with covid-19 – have published their testing protocols and statistical analysis plans.

However, given the broad outline of the vaccine trial design – including the federal clinical trial registry – important details remain a mystery.

For example, Pfizer’s chief executive has stated that the company may apply to the FDA for emergency authorization of its vaccine in early October. But the company did not state how often – and at what point of the test – it would allow an independent review board to examine its study data to evaluate whether the evidence for safety and efficacy are strong enough to allow it to test Can stop early and apply for emergency approval from federal regulators.

And no company has published the criteria they would use to determine whether these outside boards would recommend stopping the test, which could happen if the vaccine showed excessive efficacy, if it showed that it was covid – 19 against or if it did not protect. Is associated with serious security issues.

These so-called interim analyzes are of intense interest, as they are the only way that late-stage tests can be stopped early.

Company executives have provided some test details when they have spoken at discussion panels or investor conferences, or in news releases. But researchers looking for clues have had to comb through tapes, videos and articles posted online rather than examining documents provided by companies.

The lack of transparency is unacceptable, many researchers said, noting that the federal government has signed billions of dollars of deals with each of the companies.

“Look, we paid for it,” Saad B., director of the Yale Institute for Global Health. Omar said. “So it’s fair to ask for it.”

A federal clinical trial registry details the number of trial participants who should be included and excluded from the study, and the main results. But it only hollows the surface, Drs. Krumholz said. “Protocols are much more detailed.”

Peter Doshi, who is on the faculty of the Maryland School of Pharmacy in Baltimore and an editor of the medical journal BMJ, said he recently requested protocols from Pfizer, Modern and AstraZeneca. Neither company shared them, he said.

“I think the majority of the public believes that scientists are all sharing their data, that this process is open to investigation among the scientific community,” Dr. Said Doshi, who has helped drug makers share test records with researchers. “Just not true.”

Dr. Doshi said that the protocol could help researchers answer important questions about the study, and possibly criticize them. For example, can tests determine whether the vaccine can inhibit Kovid-19 and prevent complications in high-risk groups, like older adults? When researchers test for coronaviruses, how do they account for incorrect results?

Other independent scientists said they were eager to examine the statistical analysis plans of the tests, which would guide them in analyzing the results.

“Frankly, I’d love to know what they plan to do, and how they plan to do it,” Dr. Said Judith Feinberg, vice president for research in medicine at West Virginia University in Morgantown.

By making these documents public, outside experts said they could hold companies accountable if they analyzed the results.

“There is no negative aspect” to the sharing of documents, Professor Dr. of the University of Pennsylvania in Philadelphia, Drs. Paul A. Said Offit, who serves on the FDA advisory committee that will review coronovirus vaccines. “People are worried about these vaccines. I think it helps to be transparent. “

Dr. Omar said he was in favor of companies issuing protocols and analysis plans, but added that he also worried that, in the wrong hands, technical documents could be misinterpreted.

“You can’t have kids around with this kind of stuff,” he said. In the long run, however, he said it was to the benefit of the companies to allow qualified researchers to evaluate the plans.

If independent researchers agree that the tests were set up properly – and Drs. Omar said he hoped that would be the case – which could help increase his credibility. They may say: “Hold your horses. No need to jump up and down. “

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