How to read results from COVID vaccine trials like a pro



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Adrian Esterman, University of South Australia

It’s been a busy week or so for news about COVID vaccines. First we heard preliminary clinical trial results from the Pfizer vaccine, then the Russian Sputnik V vaccine. This week, we heard about the Moderna vaccine. All these results were shared with the media, ahead of being peer reviewed and published in a journal.

As we expect preliminary results from more vaccine trials to be released in the coming weeks and months, it’s important to understand what’s behind these announcements, what news reports don’t tell us, and what researchers don’t yet know.

This can help us identify good news when we see it, be more critical of news reports, or delay our judgement until we have more information.




Read more:
We may have to accept a ‘good enough’ COVID-19 vaccine, at least in 2021


1. Does the news report tell me what type of trial it is?

At this stage of the pandemic, trial results making the headlines are generally the interim results of late-stage clinical trials, known as phase 3. This is when a vaccine is given to thousands of people and tested for how well it works and whether it’s safe (more on these issues later).

In these trials, volunteers are randomised into two study arms, the vaccine arm (people who get the actual vaccine), and the placebo arm (people who get the placebo, usually an inert substance, such as a saline injection). However, some vaccine trials use vaccines against other diseases as the placebo.

So, ideally, media reports should mention how the vaccine results compare with the placebo or the comparator vaccine.




Read more:
Explainer: how do drugs get from the point of discovery to the pharmacy shelf?


Before the vaccine gets to this stage it will have successfully completed smaller trials (phase 1 and 2). Often, clinical trial phases are combined. So you could have results from a trial that combines phases 1 and 2, or phases 2 and 3.

2. Does the media report mention safety?

As vaccines are mainly tested on healthy volunteers, it is extremely important to demonstrate the vaccine is safe.

Side effects (also called adverse events) are reported to an independent committee — usually with two or more experts in immunology and medicine as well as a biostatistician. It’s one of the jobs of this data monitoring committee to receive and examine reports of adverse events, and to look at interim results to determine whether the trial should continue.

Sometimes, if safety concerns are raised, a trial is temporarily halted while the committee investigates. This is what happened with the University of Oxford/AstraZeneca vaccine trial, which has since recommenced.

So any media report should mention how many people are affected by side effects, the type of side effects (common/rare, serious/minor), whether they were in people in the vaccine or placebo arm of the trial, and whether the data monitoring committee is investigating. Not all these details are available to the public.




Read more:
Halting the Oxford vaccine trial doesn’t mean it’s not safe – it shows they’re following the right process


3. Does the media report mention how well the vaccine works?

Trial outcomes are measured at one or more interim time points, and at the end of the trial. This is another factor the data monitoring committee oversees.

For instance, the committee has rules about vaccine efficacy it applies part-way through the trial to work out whether the trial proceeds. So a rule might be something like “For the trial to continue, vaccine efficacy must be at least 60% after 25% of subjects have completed the trial”.

The types of results making the headlines currently come from this type of interim analysis. In other words, the committee will have assessed the results so far and will have given the trial a green light to proceed.

No phase 3 clinical trial has yet reported the full analysis from tens of thousands of study participants, but this will happen over the next few weeks.

Green traffic light against backdrop of cloudy sky
An independent committee analyses interim results to give the trial a green light to proceed.
Shutterstock

Vaccine efficacy

Vaccine efficacy describes how well the vaccine offers protection against the target disease. The formulae and calculations can get quite complicated, so I will only give a simple example here.

One measure is based on the “attack rate”, which is the proportion of the people in the trial diagnosed with COVID-19. We measure the attack rate in the vaccine arm and the placebo arm separately, then divide one by the other to give the “attack rate ratio”. We then subtract the attack rate ratio from 1 to get one measure of vaccine efficacy.

For example, if 5% of the vaccine arm are diagnosed with COVID-19, while 40% of the placebo are diagnosed, then the attack rate ratio is (5%/40%) or 0.125 or 12.5%. That gives a vaccine efficacy of 87.5% (100% – 12.5%).




Read more:
Pfizer vaccine: what an ‘efficacy rate above 90%’ really means


Immune response

Some vaccine trials report how well the immune system responds (immunogenicity). For example, the University of Oxford/AstraZeneca trial has reported the antibody response as well as several other measures of immunogenicity.

Some trials only report on immunogenicity. This allows the trial to be smaller, shorter, and less expensive than vaccine efficacy trials, as they use immunogenicity as a surrogate for vaccine efficacy.

Although efficacy is the preferred endpoint for vaccine trials, some regulating authorities accept evidence of immunogenicity to authorise a vaccine.

Vaccine effectiveness

Vaccine effectiveness describes how well the vaccine offers protection against the target disease in the real world, rather than in a controlled clinical trial. Vaccine trials usually include healthy volunteers, but often don’t tell us how well the vaccine works in children, elderly people, or those with compromised immune systems.

Reported vaccine efficacies of 90-95%, as we’ve heard recently, may sound impressive. However, under real-world conditions, the vaccines are likely to offer much less protection in some population groups.




Read more:
5 ways our immune responses to COVID vaccines are unique


4. What else do I need to know?

Current trials are reporting whether or not a vaccine prevents COVID-19 (in other words, symptoms), not whether it prevents the infection itself.

However, a recent media report about the Pfizer vaccine says it is likely to prevent 50% of infections, as well as 90% of symptomatic COVID-19.

If the vaccine has 90% efficacy, then 10% of vaccinated people could still get the symptomatic disease. We would hope these people would have a much milder illness, but we don’t know if this is the case.

We also don’t know how long immunity lasts or if there are any long-term side effects.

All we can do now is wait with patience for the full phase 3 trial results to come in over the next few weeks.The Conversation

Adrian Esterman, Professor of Biostatistics and Epidemiology, University of South Australia

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Selling the iPad


The link below is to an article that really covers some of my thoughts concerning Tablets, smartphones and PCs (Lap Top in my case). As in the article, I also find my iPhone and Lap Top are pretty much all I need – though I also have a Kindle (for reading ebooks only). I just can’t see how a Tablet can cut it with the various tasks I have to perform on the computer, such as a lot of keyboard activity.

What do you think? I’d be interested in your thoughts – please share in the comments.

For more visit:
http://au.businessinsider.com/why-i-sold-my-ipad-2013-7

Plinky Prompt: 10 Things That Make Me Happy


These are not necessarily on order.

Jesus
He saved me.

Coke
I just love this drink.

Bible
The book of Jesus – see point one.

Friends
Good Company helps bring a good life and experience of it.

Work
I enjoy my work.

Internet and Computer
Enjoy my various pastimes with these – websites, Blogs, etc.

Wilderness and Camping
I just love getting away and enjoying the bush.

Reading
I love to learn.

Music
I love a good modern ballad.

Photos
I love to remember good past experiences.

Powered by Plinky

Christians suffer in Iran’s ‘free nation,’ says Open Doors USA


Iran’s president claimed his country is a genuine cradle of liberty. President Mahmoud Ahmadinejad is in New York for the annual meeting of the UN General Assembly, reports MNN.

Ahmadinejad insisted that political opponents are free to demonstrate, refusing to acknowledge that opposition groups and Christians have been driven underground by a vicious government crackdown.

"When we discuss the subject of freedoms and liberty it has to be done on a comparative basis and to keep in mind that democracy, at the end of the day, means the rule of the majority, so the minority cannot rule," Ahmadinejad said.

President of Open Doors USA Carl Moeller says, "Any person that’s had any exposure to the realities of life in Iran would disagree with President Ahmadinejad."

Moeller says Ahmadinejad is the master of the big lie. "He’s a holocaust denier, for example. And it’s easy to deny something as long as you don’t have to [back it up with] evidence. In this case, it’s easy to say Iran is a free country because everybody who would dissent knows clearly that if they dissent, they would be sent to prison."

Iran is one of the most repressive places to be a Christian. It ranks second on Open Doors’ World Watch list of countries which persecute Christians. "We’ve talked, on this program, about those who have spent months in prison simply for converting to Christianity and suffered huge abuse because of it," says Moeller.

Despite this oppression, Moeller says many Iranians are turning to Christ. They’re responding to Christian radio and satellite television broadcasts. Some are reading about Christ on the Internet. Some young people are starting churches as a result.

Moeller says most Iranians are aware of it. "90 percent of Iranians are aware that Muslims are turning to faith in Jesus Christ and have first-hand knowledge of that. It’s an incredible statistic. And we see that the increase in persecution is a direct relationship with the growth of the church in Iran."

Report from the Christian Telegraph

Plinky Prompt: What Book Could You Read Over and Over?


This is my favorite book of all time.

Old Bible

This is an easy prompt to answer – it has to be the Bible. I follow the Robert Murray McCheyne Bible reading plan which takes me through the Old Testament once every year, the New Testament twice a year and the Psalms twice a year.

50 000 Visitors


The Random Thoughts Blog has reached something of a milestone – we have now had 50 000 visitors since we moved to the WordPress.com blogging platform. This isn’t a huge number of visitors when compared/contrasted with other sites, but it is still a big thing for this Blog. I wasn’t sure how many visitors we would get – I certainly wasn’t expecting that many. So thank you to everyone who has ever visited the site – even if you weren’t among our happier site viewers.

To mark this occasion I have changed the appearance of the Blog, to one that I hope is aesthetically more appealing and that will making the reading experience here so much better. The previous red-coloured links were getting to me, so I think this new look improves the reading experience here. Hopefully that proves to be the case. I do prefer the more clean approach to a Blog – much like a magazine or article in a book. It just allows me to enjoy the reading experience without having to struggle to stay focused on what I’m reading.

Anyhow – thanks again – and please come back.

A Problem with Expository Preaching?


I have recently come across an article on the Banner of Truth website that ‘deals’ with expository preaching, or rather, attempts to define the dangers of what goes by ‘expository preaching’ in this day and age. The basic explanation or definition given in the article is pretty good really – that of a preacher confining himself to the text of Scripture and making it plain to others. That in itself is a fairly good explanation of being ‘expository’ I think. I do however think that some other things are probably required to fulfill the definition of what preaching ought to be – such as there being a place for application to the listeners, etc.

My point of disagreement with the article in question, is that of the need to issue a ‘caution’ to what goes by expository preaching today, which according to the article is the method of preaching through a passage or a book of Scripture week by week. I have no issue with saying that this is not the only way of being expository, but to issue a caution about the ‘modern way’ seems somewhat extreme to me.

I wouldn’t say that the ‘modern way’ is the only way to preach, nor would I go so far as to say it is the best way of preaching. I would say that I find it the best way of preaching for me, but I wouldn’t lay it down as a rule for others. I think the method of preaching used by a preacher is best left to that preacher and between himself and the Lord. I don’t think I would even call most of the preaching of Charles Haddon Spurgeon expository, yet you cannot argue that he didn’t preach in a manner used of God. So I think caution needs to be used in laying down ‘rules’ as to what method of preaching is best for a preacher, etc.

I have heard ‘preaching’ that has been systematic in its approach to a book of the Bible and it has left me bored, dry and thinking ‘what was the point of listening to it.’ However, as a person commented on the Banner of Truth article, this has probably got more to do with the validity of the preacher’s call than anything else. Perhaps the preacher is in a not so good place before God at the time of preaching also. Who knows – but a bad experience of someone ‘preaching’ systematically through a book of the Bible or passage doesn’t necessarily mean that that method is therefore proven to be a bad one. There are other variables that come into the picture.

So the Banner of Truth article is probably leading off in the wrong direction in my opinion. Readers of this Blog can make up their own opinion by reading the said article at:

http://www.banneroftruth.org/pages/articles/article_detail.php?1777

Christian Who Fled Iran Wins Asylum in Kenya


Judge rules Iranian convert from Islam requires protection from persecutors.

NAIROBI, Kenya, March 15 (CDN) — Mohammad Azbari, a Christian convert  from Islam who has fled to Kenya, knows what it’s like to be deported back to his native Iran.

When it happened in 2007, he said, Iranian authorities pressured the government of Norway to return him and his wife Gelanie Azbari to Iran after hearing rumors that he had forsaken Islam.  

“When we arrived in Iran, we were interrogated by security and severely beaten,” he told Compass in Nairobi, where he and his family fought to persuade the Kenyan government to decline Iran’s demand to deport him back. “My son got scared and began urinating on himself.”

A cousin managed to secure their release, but not before Iranian authorities had taken valuable – and incriminating – possessions.

“They took everything that I had – laptop, camera and some of my valuables which contained all my details, such as information concerning my baptism, and my entire profile, including that of my family,” Azbari said.

Azbari had been employed in the Iranian army before fleeing, he said, and authorities were monitoring his movements because they were concerned that, having left Islam, he might betray his country and reveal government secrets.

When he and his Christian wife, a native of the Philippines, first fled Iran in 2000, he was still a Shia Muslim. The previous year authorities had arrested his wife after finding a Christmas tree in their house in Tehran; Azbari was not home at the time and thus escaped arrest, but as authorities took his wife away they left their then 3-year-old son unattended.

“I was put in a small cell for two days,” Gelanie Azbari told Compass, through tears. “While in the cell two police guards raped me. It was the worst of all the nights I have had in my lifetime. Since that time I have been sick both physically and mentally.”

Authorities soon took her husband in for interrogation, suspecting he was a spy for foreign states.

Still a Muslim, Azbari allowed his wife to follow her Christian faith. He had grown accustomed to watching her pray as a Christian and watch the Jesus Film. As time went by, he developed an urge to embrace Christianity. They started reading the Bible together.

The idea of trusting in and following Christ filled him with fear, as it was against the law to convert from Islam – it would mean losing his life, he said.

“I started questioning our leaders, who see themselves as God,” he said. “The claim of Jesus as the prophet as well as the Word and spirit of God is indicated in the Quran. When I read in the Gospels of Jesus giving people rest, it made me want to decide to accept him as my Lord and Savior.”

Sensing danger, the family fled to the Netherlands in 2000, and it was there that Azbari embraced Christianity. In 2003 the family left the Netherlands for Norway.

Azbari was an avid student of his new-found Lord; while in Norway, he became seminary teacher of Christology.

Throughout, Azbari said, the Iranian government had been monitoring his movements. In 2007 Iranian officials persuaded the Norwegian government to send him, together with his wife and son Reza Azbari, back to Iran.

After their interrogation and mistreatment upon arrival in Iran, Azbari managed to call his sister, who connected him with the army general cousin who helped secure their release. His sister took them in, but his brother in-law was not happy with their Christian prayers; he began quarreling with his wife, Azbari’s sister.

“They began looking for trouble for us,” Azbari said. “Sensing danger, we then left the home and went to find a place to stay. Everywhere we tried to book in we were rejected, since we were people who had been deported.”

They began attending a church made up primarily of foreigners, where Azbari’s wife and son felt more at home than he did. His army general cousin found out and, angry that they had sought refuge in a church after he had secured their release, grew furious.

“He was very angry, as they had also discovered this information from the laptop they had confiscated and threatened that I should be arrested,” Azbari said. “I then decided to move to central Iran to look for employment, leaving my family behind.”

The couple felt they could not go to Gelanie Azbari’s homeland as the Philippines has such friendly relations with Iran, he said.

“To go back to Philippines or Iran is quite unsafe for us,” Azbari said.

In October 2009, his sister notified him that police were looking for him and his family.

“I then decided to flee the country through Turkey, then to Kenya where I was arrested and then deported to Turkey,” Azbari said. “In Turkey they could not allow me to enter the country, hence I was returned to Kenya.”

They were arrested in January for illegal entry into Kenya. On March 4, a judge at Chief Magistrate Court No. 3 of Kenya dropped the charges against him, declaring that Azbari required international protection from his persecutors. The court also directed that Azbari be given back all his documents and the 10,000 Kenyan Shillings ($US130) in bail he had deposited.

They had applied for asylum with the United Nations. Appearing before the court on behalf of Azbari on Jan. 15, a representative of the U.N. High Commissioner for Refugees had argued that he deserved asylum because his religious status had forced him to flee from his country of origin. On March 4 the court found that Azbari and his family require international protection under Section 82 of the laws of Kenya, and he was set free.

“We have witnessed the love of God and the sacrifices of what it means to love one in word and deed,” Azbari said moments after the decision. “We saw the love of Christ from the people who understood and stood with us.”

He thanked friends who introduced his family to Nairobi Pentecostal Church, which provided them spiritual strength. Three attorneys represented Azbari: Wasia Masitsa, a legal officer for the Urban Refugee Intervention Program; Christian lawyer John Swaka; and Laban Osoro of the United Nations. Rene Kiamba of the International Christian Chamber of Commerce had helped him post bail.

Report from Compass Direct News