No News is Good News

Yes – of course this is a Covid-19 post. 

However, I’m not going to simply highlight the over-rich daily diet of mortality rates and pictures of people spectacularly breaking lockdown rules. 

This time, its why falling virus numbers could be bad news after all…

Professor Adrian Hill leads the Oxford team who were one of the front runners in the race to develop a successful vaccine. His team’s vaccine, ChAdOx1 nCoV-19, looks extremely promising. Prof Hill said a few month’s back that he felt there was an 80% chance it could form the basis of an effective vaccine by September.

So why is he now saying that there is only a 50% chance of having any result at all?

The reason is that it’s becoming increasingly hard to recruit the 10,000 adults and children the study needs.  As he told the Daily Telegraph –

“it’s not a race against the other guys. It’s a race against the virus disappearing, and against time.”

Hill’s team is working with AstraZeneca to develop the vaccine, and the UK government has already signed up for up to 100 million doses.

Just last month, AstraZeneca were hoping for answers on vaccine efficacy in June or July. It now seems the process could take far longer, unless transmission rates stay high.

Falling transmission rates may seem like a good thing, but those who fall into the category of extremely vulnerable, really need a viable alternative to solitary confinement.

One way out of the mire is to intentionally infect healthy volunteers with a weakened version of Covid-19. These so-called “human challenge studies” (HCS) are somewhat controversial – especially as some of the participants would, by design, receive a placebo followed by the virus.

This does seem to be somewhat stretching the 3rd principle of GCP – that the rights, safety and wellbeing of the trial subject is more important than the interests of science or society.

In April, the US FDA was sent a letter from 35 US Representatives urging it to take nothing off the table in searching for a Covid-19 treatment – including HCS. They see no inherent ethical problem in HCS, believing the benefits outweigh the risks.

The US vaccine expert, Stanley Plotkin, and New York University bioethicist, Arthur Caplan, argue for HCS in upcoming article for the journal, Vaccine. They argue that if the normal process is followed it –

“…normally takes months to years, during which SARS-2 will infect and possibly kill millions.”

They see human challenge trials as a way of speeding things up.

So the next time you hear the news that infection rates are falling, just pause before celebrating too loudly.

Posted by Ashley Smith on 26th May 2020

What happens to other research when all eyes turn to Covid-19?

Coronavirus research is at the forefront of everyone’s minds, but what about non-Covid medical trials? With resources channelled into treatments for the pandemic, what impact is this having on other research projects?

Infonetica provides online medical research training, so we’ve had our share of conversations with companies whose research programmes have been massively disrupted. However, you can’t just pause some trials without serious consequences.

A recent article in the journal, Science, highlighted the case of US HIV prevention trials that are still going on albeit with some creative measures.

“…study teams have bought and shipped protective equipment to personnel at clinical trial sites, secured special permits where necessary for trial participants to leave their homes for medical visits, and arranged their private transportation to avoid public buses.”

Clinical trials press on for conditions other than COVID-19. Will the pandemic’s effects sneak into their data? Science, 6th May 2020 

It went on to suggest that the effect of the pandemic on mental health should be factored into the equation too.

But is this even possible?

The primary aim of GCP is to protect patients and to do what is in their best interests. Clearly just stopping treatments isn’t in most patient’s best interests.

What about those at particular risk from Covid-19 infection?

In the UK, patients receiving treatment for auto-immune conditions are automatically considered high risk and advised to “shield” – effectively being advised to go into isolation apart from medical intervention. But there are inconsistencies even in this approach – for example, patients with untreatable auto-immune conditions, are not currently being told to shield.

The key problem, as I see it, is that all good science involves controlling a limited number of variables so you can measure the effect of change. However, this assumes that the other variables remain fixed.  During the pandemic, the situation is so massively divorced from “normal” that there is a real risk of findings being un-reproducible in a post-Covid world.

I’ve already mentioned the effect of the pandemic on mental health, but what about the reduced likelihood of being exposed to pathogens (important in the HIV trial), changes to diet, changes to exercise levels etc?

The list goes on…

I fully understand and support the need to “keep on keeping on” and we can’t just stop everything and hunker down till the tornado passes, but just how we’re going to look back on this period – that’s anyone’s guess!

Posted by Ashley Smith on 7th May 2020

Research ethics are especially relevant in the face of pandemics

Newly emerging pandemics like Covid-19 raise many ethical issues for medical staff. Especially – If there are no available treatments, should you improvise based on anecdotal evidence? As with most ethical issues – the answers are not clear.

 

On the one hand we have US President Donald Trump – who applies the quick-fix logic of a businessman surrounded by staff to handle details. Sometimes suggesting weird, off the wall things can be just what’s needed to boost innovation. As long as people don’t then take matters into their own hands and try swallowing bleach because they think the President suggested it!

On the other hand, we have the tried and tested approach of Good Clinical Practice and rigorous double-blinded trials. These are the bedrock of medical research and represent the safest way forward. However, double blinds become problematic where there is no “standard” treatment to compare with a test drug.

Doctors at the sharp end of pandemics like Covid-19 are faced with a stark choice – try something they think might work or carry on trying to support the patient until the recover. Some of the earliest Covid-19 patients in China, were given the anti-retroviral drug, lopinavir–pitonavir, and the rheumatoid arthritis drug, Actemra (tocilizumab).

The important point here, is that the drugs were controlled and the patients observed. There are no placebos in the true sense – the control group were given ventilation and other support but not specific control drugs.

This approach has been followed in other pandemics, and The WHO’s Covid-19 trials are not double-blind because they argued that they needed to balance rigor with speed.

So where does this leave ethical review?

We all know the story of the tortoise and the hare. Rushing full tilt into drug testing can actually delay things according to Rebecca Li, executive director of the Multi-regional Clinical Trial Center at Harvard University.

She points out that the vast majority of experimental drugs do not succeed. Without properly reviewed and planned trials, researchers risk going down rabbit holes and wasting valuable research effort. It is hard not to get carried along by the overriding sense of urgency that is gripping the healthcare sector, but this does not mean ethics should go out of the window.

Sure, rely on the most efficient ethical review tools at your disposal to reduce wasted time but don’t throw the baby out with the bathwater. If you can find ways to speed up peer view processes for example – use them!

Follow Good Clinical Practice, rely on tools like Ethics Review Manager and be pragmatic.

Otherwise we might just end up swallowing bleach…

Posted by Ashley Smith on 24th April 2020

Free Covid-19 testing support from Infonetica

Like everyone, we at Infonetica want to help assist in the current Covid-19 crisis. Tissue Auditor is already being used to help UK Covid-19 testing so we are making it more widely available.

Our tissue tracking software, Tissue Auditor is being used by two major testing sites in the UK to manage samples and we have decided to make it available for ANY organisation working on Covid-19 testing or research free of charge.

Our system offers these benefits –

• web-based – no time-consuming installation and can be used on virtually any device.
• single sign on – so staff can use their existing login credentials.
• works with RFID tags, or 1D/2D barcodes
• full audit history from sample creation to destruction.
• keeps all documents in one place for easy cross-referencing.

If your organisation might benefit from Tissue Auditor or if you could pass this message on to any of your contacts who may – that would be great.

Email: rodney.clark@infonetica.net for more information.

Posted by Ashley Smith on 23rd April 2020

The Anti-Vaccination Movement: Disrupting Global Health

Vaccination is one of the most cost-effective ways of avoiding disease, currently preventing 2-3 million deaths a year. This figure could increase to a further 1.5 million if global coverage of vaccinations improves.

However, the anti-vaccination movement has been growing in recent years. The World Health Organization (WHO) now list it as one of the top 10 potential threats to global health in 2019.

The dangerous implications of this growing vaccine hesitancy can be clearly seen in the Philippines. Earlier this year an outbreak of the highly contagious measles virus infected over 8,000 people. More than 130 of these died, and sadly many of them were children.

This measles outbreak arose in response to complications related to a dengue vaccination, Dengvaxia. Developed by a French drugs manufacturer, the vaccine reportedly offered protection against the potentially fatal mosquito-borne disease, Dengue Fever. In an attempt to mitigate the disease, Philippine authorities provided over 800,000 children with the vaccination in 2016. However, a year later it was revealed that this vaccination could potentially worsen the deadly disease in those who had not previously been exposed to the virus. This side effect unfortunately resulted in 14 deaths.

The immense effect that this scare has had on the country is highlighted by the rapidly decreasing immunisation rate, falling from 75% in 2016 to just 60% in 2017. This decrease makes potentially fatal outbreaks of otherwise preventable diseases ever more likely.

Unfortunately the Philippines is not the only country to experience the negative implications of the anti-vaccination movement first hand. It was recently reported that there has been a measles outbreak in Hackney, London. As a result local parents are being urged to keep their children’s vaccinations up to date.

The increasing frequency of these outbreaks across the world highlights the negative impact that vaccine hesitancy is having on a global scale. Unfortunately more and more lives will be put at risk if the anti-vaccination movement continues to grow at its current rate.

This article is the first in a two part series on the anti-vaccination movement. To read the second installment please click here.

If you are interested in learning more about protecting yourself in the event of an outbreak, then take a look at our infection prevention and control course.

Posted by Kallie Price on 25th March 2019

Flu: Is Llama Blood the Answer?

Flu: Are Llamas the Solution?

The annual flu season is upon us and many of us get vaccinated against prevalent strains of influenza, identified from the southern hemisphere’s winter. Flu is caused by a virus that has the ability to mutate quickly, regularly leading to new strains and the possibility of outbreaks each year.

What flu researchers are hoping for is a vaccination that could combat all strains of the virus, to reduce, or even eliminate, the need for yearly vaccinations. Up until now, such a solution has proved elusive, but recent research published in Science suggests the answer could lie with llamas!

Whilst humans produce large antibodies that attack flu antigens directly, llamas produce much smaller antibodies that target harder to reach areas of the virus. Areas that don’t mutate regularly. Researchers at the Scripps Institute in California examined the numerous antibodies present in llama blood, finding four that could potentially fight flu in humans. These four antibodies were effective on all but one of the sixty variations of flu they were tested on.

Yet what’s especially interesting about the research, is its possible application. The research suggests that an effective delivery method could use gene therapy. This would be particularly beneficial for the elderly, as traditional vaccinations become less effective as the efficiency of the immune system declines. The use of gene therapy could mean targeted cells can immediately produce the desired antibodies of their own accord.

Whilst the initial results are encouraging, the study is still ongoing. If upcoming human trials are successful, then the goal of producing a vaccine that would be effective for multiple seasons, might not be so far off. But as research continues, the question remains are we doing enough to protect the most vulnerable in society, from what can be a deadly illness.

To learn more, take a look at our Infection Prevention and Control course!

Posted by Sophie Griffith on 8th March 2019

Is gene editing one step too far?

Gene editing could eliminate some diseases – but at what cost to the future of the human race? What is the true risk of gene editing?

Originally discovered by a researcher from Osaka University in 1987, gene editing could potentially be used to eliminate heritable diseases through deleting or changing certain coding in embryos. However, the technology involved in this editing is still in the experimental stages, and as such is currently banned in most countries. There is a fear that the changes in DNA could be passed on to future generations, with unpredictable side-effects.

It appears as though these fears are about to be put to the test for the first time in history, as a scientist in China has recently claimed to have produced the world’s first genetically-edited babies. This is yet to be verified, however, if confirmed it could have immense ethical and moral implications.

He Jiankui, a professor from The Southern University of Science and Technology in Shenzhen, is claiming to have edited embryos for seven couples during fertility treatment. According to him, one pregnancy has resulted from this so far.

Jiankui revealed that all of the men in his experiment had HIV while all of the women did not. However, the fathers’ infections are deeply suppressed thanks to standard HIV medicines. Simple methods exist to prevent them from infecting their offspring.

The existence of these treatments mean that the scientist’s intervention was not aimed at preventing HIV transmission. Instead, he hoped to provide the offspring with protection against the disease, reducing their chances of contracting it during their lifetime.

This breakthrough intervention has raised many ethical questions.

Any editing errors within the genes could have potentially fatal effects on the growth of the foetus.

Experts worry that we won’t know the full consequences of this gene editing until we can study future generations of the offspring concerned. Even if the editing works perfectly, people without normal genes may be at a greater risk of contracting other viruses.

Ethical questions have also been raised regarding consent. With the consent forms referring to the experiment as an Aids Vaccine Development Programme it is likely that the participants were not made fully aware of the potential risks of the study.

What is particularly shocking is the fact that Jiankui’s work remained a secret for so long. He did not register the clinical trial with Chinese authorities until November, long after the study had begun.

As a country that has been at the forefront of gene editing for several years, China has failed to update its regulations at the same pace, to reflect the risk of gene editing. A 2003 ‘ethics guidance’ document bans the use of research embryos for reproduction. However, the punishments for violations of this regulation remain unspecified.

While China have declared He Jiankui’s work a violation of their law, the incident serves to highlight a concerning gap in their ethical review processing.

Here at Infonetica we have been developing systems to manage the ethical review process for over ten years. With the ethics debate widening, our Ethics Review Manager (ERM) software can manage the processing of ethical decisions for a wide range of organisations.

Posted by Ashley Smith on 10th December 2018

Is the gender gap an issue in medical trials?

It is well accepted that children are not just miniature adults and so ideally should only receive drugs that have been tested in paediatric trials. However, there is also evidence that the difference between male and female patients can be just as important.

Sleeping pill, Ambien, is a good example of a drug that works differently in men and women. The US Food and Drug Administration (FDA) discovered that men metabolize the drug much faster than women. This led to the FDA cutting recommended doses for women by half.

Even the humble aspirin has very different effects on men and women in terms of lowering risk of heart disease.

Findings like these prompted the FDA to release a set of guidelines to the pharmaceutical industry detailing the exceptions for excluding a gender from clinical trials, such as testing a prostate cancer medication or other male or female-specific drug. In theory, women have been included equally in drug studies since 2001.

However, a report in the journal, Cell Metabolism, suggests that there is still a long way to go to eliminate the gender gap in medical trials. According to the report, there is still a tendency to treat the sexes as equivalent, ignoring how fluctuations of sex hormones in experimental settings impact outcomes.

The authors of this article are not alone – an article published in the journal, Cancer, also points to a gender bias in oncology trials – excluding those cancers that only present in a single sex of patient of course.

I have written before about the massive under-representation of ethnic minorities in drug trials and the actions to address this in the US. However, the difference between male and female patients is less widely reported.

Is this, as some article have suggested, because things like periods and menopause make female trial participants a more unpredictable proposition? I certainly hope not.

I suspect is it largely the fact that white, middle-aged men are the easiest (and therefore cheapest) group to recruit. Recruitment is one of the most time-consuming and expensive parts of a drug trial – failure to recruit means the whole trial will collapse.

Trials have a responsibility to investigate a drug’s effect on a sample that is as close to the target market as is practically possible. It means ensuring trials are design to account for the difference between male and female patients.

Doing so will inevitable increase the cost of some trials but if the results are more representative of a drug’s behaviour in the population isn’t it a cost that is worth bearing?

Posted by Ashley Smith on 15th August 2018

What tools are ethical in the fight against anti-vaccers?

The anti-vaccination movement is a relatively new, largely US phenomenon. It has been roundly criticised in medical circles. However, it stems from a desire (albeit perhaps misguided) of parents to do what’s best for their children.

The anti-vaccination movement has snowballed from one, now totally discredited, paper into an internet full of half-truths and outright lies.

Don’t get me wrong, the internet is a largely immensely positive thing. However, giving people the opportunity to “research” subjects they know nothing about by consulting sources who have no need to be unbiased is not liberating. It is the exact opposite!

So what strategies are OK to use to persuade parents that vaccines are not only safe (relatively) but essential, rather than a tool of state control?

The argument that, without widespread vaccination, herd immunity cannot protect the few who cannot be vaccinated has been used. The counter argument is that parents see this as putting their child at risk to protect the greater good – as Mr Spock once said “the needs of the many outweigh the needs of the few, or the one.”

Even the argument that the main beneficiary of vaccination is the child themselves can be disputed as a biased statement produced by corrupt medical big business.

So is it time for a hard line approach?

Several have already been tried, from refusing access to schools, to removal of state benefit payments. However, parents who decide not to vaccinate are often relatively well off so these don’t always carry the bite they may otherwise do.

Many organisations are keen to support patents’ right to ethical and religious freedom against such draconian measures. Unsurprisingly, many lawyers are also keen to help uphold choice, for the right price. This does not mean the anti-vaccination movement is winning.

Some physicians in the US are even withholding healthcare provision unless a child is properly vaccinated.

Unfortunately, all of these measures seem to have one principle victim – the child themselves. The poor kid is already far more likely to get a potentially fatal, preventable diseases, now they won’t get proper schooling or medical care.

You’ll never forget the look of shock and betrayal that your tiny, innocent and trusting child gives you after the doctor jabs them with a needle for the first time – but I’d argue, it’s just part of growing up (yours not theirs).

Posted by Ashley Smith on 20th July 2018

Statistical analysis exposes dubious data in 2% of anaesthesia trials

Statistical analysis of over 5,000 published trials has highlighted 90 that contain dubious data.

This is equivalent to around 2% of the trials examined using statistical tools to identify anomalies hidden within the data. The authors of the study into anaesthesia trials point out that there could be many reasons for these anomalies – such as poor trial methodology, but clearly fraud is a possibility too.

All of these trials had been published in prestigious journals, including: Anaesthesia; Anaesthesia and Analgesia; European Journal of Anaesthesiology; Journal of the American Medical Association; and the New England Journal of Medicine.

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John Carlisle, a consultant anaesthetist at Torbay Hospital, carried out the analysis. He had previously used similar statistical tools to discover a high profile case of scientific fraud involving a Japanese anaesthesiologist who was found to have repeatedly fabricated data.

The tool works by comparing the baseline data, such as the height, sex, weight and blood pressure of trial participants, to known distributions of these variables in a random sample of the populations. This is a test hyperlink

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Carlisle reviewed data from 5,087 clinical trials published during the past 15 years. He concluded that 90 published trials had underlying statistical patterns that were unlikely to appear by chance in a credible dataset.

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“For 50 years, WWF has been protecting the future of nature. The world’s leading conservation organization, WWF works in 100 countries and is supported by 1.2 million members in the United States and close to 5 million globally.”

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The data in 43 of the trials had only about a one in a quadrillion chance of having occurred by chance.

I wonder how long it will be before a statistical tool is developed to massage falsified data so it is harder to detect? Not that I’m a pessimist of course…

Posted by Ashley Smith on 19th February 2018