'There is currently no indication that the vaccination has caused these conditions, which are not listed as side effects with this vaccine', says European Medicines Agency

European Medical Agencies backs AstraZeneca vaccine after suspensions

About 1,500 of the initial volunteers in a late-stage clinical trial of the Oxford-AstraZeneca COVID-19 <a href="https://www.wionews.com/world/powerful-snowstorm-disrupts-covid-19-vaccination-drive-in-new-york-360755">vaccine</a> were given the wrong dose, but weren't informed that a mistake had been made after the blunder was discovered, documents obtained by Reuters show.

The dosing mishap was presented to the trial participants in a letter dated June 8 as an opportunity for University of Oxford researchers to learn how well the vaccine works at different doses. The letter was signed by the trial's chief investigator, Oxford professor Andrew J. Pollard, and sent to the trial subjects.

As Reuters reported on December&nbsp;24, participants were given about a half dose due to a measuring mistake by Oxford researchers. The Pollard letter didn't acknowledge any error. Nor did it disclose that researchers had reported the issue to British medical regulators, who then told Oxford to add another test group to receive the full dose, in line with the trial's original plan.

There is no suggestion there was any risk to the health of trial participants.

Much is riding on the British-developed vaccine, which is being rolled out across the UK and has been touted as a low-cost weapon against the pandemic. The jab has come under scrutiny because of the dosing error in the Oxford trial and a paucity of data about its efficacy in older people who are most vulnerable to the virus.

Reuters shared the letter – which it obtained from the university through a Freedom of Information request – with three different experts in medical ethics. The ethicists all said it indicates the researchers may not have been transparent with trial participants. Volunteers in clinical trials are supposed to be kept fully informed about any changes.

"They are not clear at all about what they need to be clear about - what's going on, what they knew, the rationale for undertaking further research," said Arthur L. Caplan, founding head of the Division of Medical Ethics at New York University Grossman School of Medicine. "It is lost in a snowstorm of verbiage."

Steve Pritchard, a spokesman for Oxford, told Reuters: "The half-dose group was unplanned, but we did know in advance that there was a discrepancy in the dose measurements and discussed this with the regulators before dosing and when the dosing was revised."

Pritchard also said, "We have not stated that a dosing error occurred."

Pollard didn't respond to a request for comment.

The spokesman's suggestion that no error was made is contradicted by documents produced last year by Oxford and its vaccine partner, drugs giant AstraZeneca PLC. In December, Reuters reported that a "Global Statistical Analysis Plan" by Oxford/AstraZeneca, dated November&nbsp;17 and later published in the scientific journal The Lancet, called the dosing discrepancy "a potency miscalculation."

A spokesman for AstraZeneca declined to comment.

The Health Research Authority, a British government agency responsible for approving medical research and ensuring it is ethical, said in a statement that changes to the study design and the letter sent to participants were approved by one of its ethics committees.

The Oxford-AstraZeneca vaccine recently has received authorization for use in a growing number of countries, including the United Kingdom, the European Union and India. The UK became the first country to approve it, and began rolling out the vaccine on January 4.

But questions surrounding the clinical trials continue to plague the vaccine. Last week, Germany's vaccine committee recommended it should only be given to people aged under 65, while the EU, which authorized it on Friday for people aged 18 and over, lowered its reported efficacy rate from 70.4% to 60%.

In both cases, authorities cited a lack of sufficient data from the clinical trials. The EU also has sharply criticized AstraZeneca for cutting back its planned vaccine deliveries to the continent over the next few months. The company has said it is doing its best to boost supplies.

The mistaken half-dose – which prompted the letter in June to trial participants – continues to be a factor in the reported efficacy of the Oxford-AstraZeneca vaccine.

Oxford had reported interim results in November that showed the efficacy rate for trial subjects who mistakenly received a half-dose and a subsequent full-dose booster shot was 90 per cent, and that the rate for those who received&nbsp;two full doses was 62 per cent.&nbsp;Combining data from the two dosing regimens resulted in an efficacy of 70.4 per cent.

In authorizing the vaccine, UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), accepted the pooled results, but didn't approve administering the half-dose/full-dose regimen. "There is not persuasive evidence of a real difference in" vaccine efficacy between the two different dosing regimens, it said.

The vaccine's late-stage clinical trial began on May 28. Within days, Oxford researchers realized trial participants had been given lower doses than planned after they displayed milder than expected side effects, such as fever and fatigue. They alerted British medical regulators.

On June 5, the researchers amended the trial protocol at the request of regulators to add a new group that would receive the correct full dose of the vaccine. Three days later, they alerted trial subjects to what they called "recent changes in the study" in a two-page letter attached to an updated 13-page "Participant Information Sheet."

The letter, signed by chief investigator Pollard, stated that researchers "are not sure what dose of vaccine is most likely to be protective against COVID disease" and explained that doses "are measured using standard scientific test methods." It said the late-stage trial participants received a dose measured using one method and that another group will receive a dose measured using a different test to match the dose given in another clinical trial of the vaccine.

It said the lower dose is "still in the normal range of doses that are used in clinical trials" and "if it can provide protection, it might be better for use in vaccine programmes."

Caplan said the explanation would be of "no interest whatsoever to the subject because it's too technical. To me, that qualifies as gobbledygook. What you want to know is, why are they doing this, we made an error, it involved dosing, we're not worried about it."

He and other ethicists interviewed by Reuters said researchers are obligated to be forthcoming with test subjects when things go wrong.

"As a letter purporting to explain a) an error and b) a change of protocol I find this entirely inadequate," said Simon Woods, a professor of bioethics at Newcastle University, in an email. "It reads like a routine update (and a complex one at that)."

Emma Cave, a professor of healthcare law at Durham University's law school, said: "Presenting the dosing variation as a planned change in the study is potentially a breach of trust if in fact the dosing resulted from an error. The letter makes clear the dosing change but not the reason for the change."

About 1,500 of the initial volunteers in a late-stage clinical trial of the Oxford-AstraZeneca COVID-19 vaccine were given the wrong dose, but weren't informed that a mistake had been made after the blunder was discovered, documents obtained by Reuters show.

About 1,500 of the initial volunteers in a late-stage clinical trial of the Oxford-AstraZeneca COVID-19 vaccine were given the wrong dose, but weren't informed that a mistake had been made after the blunder was discovered, documents obtained by Reuters show. The dosing mishap was presented to the trial participants in a letter dated June 8 as an opportunity for University of Oxford researchers to learn how well the vaccine works at different doses. The letter was signed by the trial's chief investigator, Oxford professor Andrew J. Pollard, and sent to the trial subjects. As Reuters reported on December 24, participants were given about a half dose due to a measuring mistake by Oxford researchers. The Pollard letter didn't acknowledge any error. Nor did it disclose that researchers had reported the issue to British medical regulators, who then told Oxford to add another test group to receive the full dose, in line with the trial's original plan. There is no suggestion there was any risk to the health of trial participants. Much is riding on the British-developed vaccine, which is being rolled out across the UK and has been touted as a low-cost weapon against the pandemic. The jab has come under scrutiny because of the dosing error in the Oxford trial and a paucity of data about its efficacy in older people who are most vulnerable to the virus. Reuters shared the letter – which it obtained from the university through a Freedom of Information request – with three different experts in medical ethics. The ethicists all said it indicates the researchers may not have been transparent with trial participants. Volunteers in clinical trials are supposed to be kept fully informed about any changes. "They are not clear at all about what they need to be clear about - what's going on, what they knew, the rationale for undertaking further research," said Arthur L. Caplan, founding head of the Division of Medical Ethics at New York University Grossman School of Medicine. "It is lost in a snowstorm of verbiage." Steve Pritchard, a spokesman for Oxford, told Reuters: "The half-dose group was unplanned, but we did know in advance that there was a discrepancy in the dose measurements and discussed this with the regulators before dosing and when the dosing was revised." Pritchard also said, "We have not stated that a dosing error occurred." Pollard didn't respond to a request for comment. The spokesman's suggestion that no error was made is contradicted by documents produced last year by Oxford and its vaccine partner, drugs giant AstraZeneca PLC. In December, Reuters reported that a "Global Statistical Analysis Plan" by Oxford/AstraZeneca, dated November 17 and later published in the scientific journal The Lancet, called the dosing discrepancy "a potency miscalculation." A spokesman for AstraZeneca declined to comment. The Health Research Authority, a British government agency responsible for approving medical research and ensuring it is ethical, said in a statement that changes to the study design and the letter sent to participants were approved by one of its ethics committees. The Oxford-AstraZeneca vaccine recently has received authorization for use in a growing number of countries, including the United Kingdom, the European Union and India. The UK became the first country to approve it, and began rolling out the vaccine on January 4. But questions surrounding the clinical trials continue to plague the vaccine. Last week, Germany's vaccine committee recommended it should only be given to people aged under 65, while the EU, which authorized it on Friday for people aged 18 and over, lowered its reported efficacy rate from 70.4% to 60%. In both cases, authorities cited a lack of sufficient data from the clinical trials. The EU also has sharply criticized AstraZeneca for cutting back its planned vaccine deliveries to the continent over the next few months. The company has said it is doing its best to boost supplies. The mistaken half-dose – which prompted the letter in June to trial participants – continues to be a factor in the reported efficacy of the Oxford-AstraZeneca vaccine. Oxford had reported interim results in November that showed the efficacy rate for trial subjects who mistakenly received a half-dose and a subsequent full-dose booster shot was 90 per cent, and that the rate for those who received two full doses was 62 per cent. Combining data from the two dosing regimens resulted in an efficacy of 70.4 per cent. In authorizing the vaccine, UK regulator, the Medicines and Healthcare products Regulatory Agency (MHRA), accepted the pooled results, but didn't approve administering the half-dose/full-dose regimen. "There is not persuasive evidence of a real difference in" vaccine efficacy between the two different dosing regimens, it said. The vaccine's late-stage clinical trial began on May 28. Within days, Oxford researchers realized trial participants had been given lower doses than planned after they displayed milder than expected side effects, such as fever and fatigue. They alerted British medical regulators. On June 5, the researchers amended the trial protocol at the request of regulators to add a new group that would receive the correct full dose of the vaccine. Three days later, they alerted trial subjects to what they called "recent changes in the study" in a two-page letter attached to an updated 13-page "Participant Information Sheet." The letter, signed by chief investigator Pollard, stated that researchers "are not sure what dose of vaccine is most likely to be protective against COVID disease" and explained that doses "are measured using standard scientific test methods." It said the late-stage trial participants received a dose measured using one method and that another group will receive a dose measured using a different test to match the dose given in another clinical trial of the vaccine. It said the lower dose is "still in the normal range of doses that are used in clinical trials" and "if it can provide protection, it might be better for use in vaccine programmes." Caplan said the explanation would be of "no interest whatsoever to the subject because it's too technical. To me, that qualifies as gobbledygook. What you want to know is, why are they doing this, we made an error, it involved dosing, we're not worried about it." He and other ethicists interviewed by Reuters said researchers are obligated to be forthcoming with test subjects when things go wrong. "As a letter purporting to explain a) an error and b) a change of protocol I find this entirely inadequate," said Simon Woods, a professor of bioethics at Newcastle University, in an email. "It reads like a routine update (and a complex one at that)." Emma Cave, a professor of healthcare law at Durham University's law school, said: "Presenting the dosing variation as a planned change in the study is potentially a breach of trust if in fact the dosing resulted from an error. The letter makes clear the dosing change but not the reason for the change."

Volunteers in AstraZeneca trial given wrong dose, documents reveal

&nbsp;As Europe grapples with the virus, Germany's vaccine commission STIKO said the &nbsp;AstraZeneca's coronavirus <a href="https://www.wionews.com/world/pfizer-says-covid-vaccine-effective-against-uk-south-africa-mutations-359921">vaccine</a> should not be administered for those over 65 years of age.

Watch:

<div class="videoWrapper trancodeVideo"><iframe allowfullscreen="" autoplay="1" class="includeVideo" frameborder="0" height="350" src="https://www.wionews.com/videos/astrazeneca-covid-19-vaccine-supplies-to-eu-nations-lower-than-expected-359875/embed" style="width:100%;max-width:560px;" width="560"></iframe></div>

"There is currently insufficient data to assess the efficacy of the vaccine for persons aged 65 years and older," the German commission said, adding,"other than this limitation, this vaccine is considered appropriate."

The Standing Vaccine Commission at the Robert Koch Institute said the jabs should be allowed for people aged between 18 and 64 years old. The AstraZeneca-Oxford vaccine has already been approved by the UK.

&nbsp;The vaccine developed by Oxford University has not been granted approval for general use in the European Union(EU). The EU has been scrambling to get its <a href="https://www.wionews.com/world/pharma-distributors-in-talks-with-us-for-cut-of-covid-vaccine-shipping-deal-359900">vaccine</a> programme in high gear amid shortage of shots.&nbsp;

&nbsp;The EU publicly rebuked AstraZeneca for failing to deliver vaccines to the European nations and even asked if it could divert supplies from Britain. AstraZeneca CEO Pascal Soriot said the EU was late in tieing up the supply contract so the company did not have enough time to iron out production problems at its vaccine factory Belgium.

Meanwhile, Britain which had stepped out of the EU on January 1 said its deliveries must be honoured.&nbsp;

Several EU nations including France, Spain and Germany have run shot of Pfizer-BioNtech vaccines with several vaccination centres no longer taking appointments for the first jab due to delivery delays.

Portugal has also delayed its vaccination programme due to delays in delivery even as the EU warned AstraZeneca that it would use all legal means or even block exports unless it agreed to deliver shots.

As Europe grapples with the virus, Germany's vaccine commission STIKO said the AstraZeneca's coronavirus vaccine should not be administered for those over 65 years of age.

As Europe grapples with the virus, Germany's vaccine commission STIKO said the AstraZeneca's coronavirus vaccine should not be administered for those over 65 years of age. Watch: "There is currently insufficient data to assess the efficacy of the vaccine for persons aged 65 years and older," the German commission said, adding,"other than this limitation, this vaccine is considered appropriate." The Standing Vaccine Commission at the Robert Koch Institute said the jabs should be allowed for people aged between 18 and 64 years old. The AstraZeneca-Oxford vaccine has already been approved by the UK. The vaccine developed by Oxford University has not been granted approval for general use in the European Union(EU). The EU has been scrambling to get its vaccine programme in high gear amid shortage of shots. The EU publicly rebuked AstraZeneca for failing to deliver vaccines to the European nations and even asked if it could divert supplies from Britain. AstraZeneca CEO Pascal Soriot said the EU was late in tieing up the supply contract so the company did not have enough time to iron out production problems at its vaccine factory Belgium. Meanwhile, Britain which had stepped out of the EU on January 1 said its deliveries must be honoured. Several EU nations including France, Spain and Germany have run shot of Pfizer-BioNtech vaccines with several vaccination centres no longer taking appointments for the first jab due to delivery delays. Portugal has also delayed its vaccination programme due to delays in delivery even as the EU warned AstraZeneca that it would use all legal means or even block exports unless it agreed to deliver shots.

'Insufficient data': German board says AstraZeneca COVID-19 vaccine should not be used for over-65s

U.K. approval would provide vindication for the AstraZeneca-Oxford shot, which has been slowed by questions about discrepancies in the trial results.

AstraZeneca Covid vaccine to be approved by UK within days