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.
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.
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.
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.
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.
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.
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
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.
This is some bold text.
This is some italic text.
This is some bold italic text.
“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.”Kanye West, Producer.
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…
A recent report published by Doctors Without Borders titled ‘Lives on the edge’ analyses the failure of the current R&D system and goes on to outline new ways of developing tools to better address the medical needs of people at affordable prices. World governments have been urged to be proactive in the development of desperately needed new vaccines, diagnostics and medicines at affordable prices.
Doctors Without Borders is an independent international medical humanitarian organisation working to bring emergency medical care to people caught in conflict, crises, and disasters in more than 65 countries world over.
“People in poor and wealthy countries are now finding that the medicines they need either don’t exist or are priced so high that they can’t afford them, and governments need to solve these problems,” says an official of Doctors Without Borders in the report.
The report goes on to say pharmaceutical corporations woefully under-invest in research for diseases that aren’t lucrative, while governments have failed to ensure that taxpayer-funded research addresses priority health needs.
One example of this world wide crisis is in Zimbabwe, where their pharmaceutical sector is only producing eight percent of the country’s drugs, a startling indication that the country’s pharmaceutical industry is in crisis, a situation that puts their citizens under threat. Health is a sensitive topic all over the world, but for countries like Zimbabwe it is important to be able to produce the medicines necessary to provide for its people.
Most drug manufacturers in the country have closed shop because of the macro-economic environment, and the few that are left face stiff competition from cheap imports. Some of the companies that are either facing viability challenges or have closed shop include CAPS Holdings, MedTech Holdings, Wallace Laboratories, Lancaster Industries, and Reckitt and Benckiser.
The government, however, insists it is committed to promoting and encouraging the most cost effective local production of safe, high quality medicines at affordable prices.
The first, entitled “Regulatory Pathways for Medical Devices: Choosing the Right One” is intended to set the scene by describing the steps a new company may follow to bring its first product, an insulin pump, to market.
The aim of this study is:
The second study, “Freedom From Unacceptable Risk: Making a Case for Safety Assurance and Risk Management” , deals with an infusion pump company considering risk assessment and mitigation.
The learning objectives are:
The third study is called, “Bringing an Innovative Device to Market: Premarket Approval (PMA) of Medical Devices”, and covers regulatory issues raised when bringing a bare metal coronary stent device to market through the Premarket Approval (PMA) regulatory pathway.
This study’s learning objectives are:
The final study, “An innovative “Me-Too” Idea: Premarket Notification – 510(k) Medical Device Submissions” describes a hip implant company seeking to market a medical device that it believes is substantially equivalent to a Class II medical device and thus eligible for the Premarket Notification (510(k)) regulatory pathway.
The learning objectives are:
To me, the 70s soap opera style jars but there is no doubt that the information is clear and well laid out – if you have the recommended three hours to spend going each one. The following excerpt from case study one gives you a flavour…
“…And we’ll need to make sure the postmarket surveillance controls are in place, like medical device Reporting, which includes tracking of adverse events. Then we go to market with your device!”
Neyhard held up one hand. “Stop right there.”
Mooney and Laws shifted nervously in their seats. What had they missed?
To be continued…
Whitehall Trainings’ course, Device Safety & Vigilance, was written by Steve Jolley – a Cambridge University graduate with 25 years’ experience in drug & device safety & vigilance, who specializes in global safety compliance, business process improvement and signal detection. He is the Chairperson of the DIA Clinical Safety and Pharmacovigilance steering committee for North America and has worked with over 80 clients in the US, Europe and Japan. He is a featured speaker with the FDA and MHRA at DIA conferences and webinars on drug safety topics including auditing and signalling).
Safety testing of drugs can be a contentious issue – testing of non-pharmaceuticals is even more so. Opinions are especially polarised where the test systems are live animals. Understandably, such practices are tightly controlled, and this is where Good Laboratory Practice plays a vital role.
In 1976, the FDA issued the first draft of the regulations that would become known as GLP. This was largely prompted by alarming findings at a US testing lab that, at the time, carried out almost half of the world’s toxicology tests. The OECD GLP principles came a little later and form the bedrock of toxicology and environmental studies, having been passed into the legislation of many countries.
The OECD defines GLP as “…a quality system concerned with the organisational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported.” The principles are wide ranging – as the work covered varies enormously from those involving chemical tests carried out in a lab to large-scale field trials.
Whitehall Training has just published an online training course that deals with each of the following important aspects:
Like all of Whitehall’s training, the GLP course has a multiple-choice exam and a uniquely-numbered, named and dated certificate that can be used to demonstrate training compliance at audit. It has also been accredited with 6 CPD points by The Faculty of Pharmaceutical Medicine of the Royal College of Physicians of the United Kingdom.
Roger Chapman is an internationally recognised expert in the interpretation and application of OECD Good Laboratory Practice to the full spectrum of regulatory studies, both in the laboratory and in the field. He also has extensive experience of Good Clinical Practice in the laboratory (GCLP), and Good Manufacturing Practice in the Quality Control laboratory environment.
A long-serving former Senior Quality Assurance Manager in the Contract Research industry, Roger has developed a tremendous depth of experience in compliance problem-solving. He has also led or participated in over 70 regulatory inspections from the MHRA, FDA and EPA, and has developed and maintained GxP quality systems and audit programmes for over 30 years.
Roger is a regular speaker at regional, national and international conferences and an established trainer/facilitator on professional development courses covering Quality, Compliance and Quality Assurance.