Researchers evaluating a random selection of clinical trials done in North America found that they neglected to take into account previous or ongoing trials, which may result in researchers conducting redundant or less impactful studies. The findings were published in the journal Med.
Clinical trials are a crucial tool for assessing the safety and efficacy of medical interventions, but sponsors often provide incomplete information for assessing their ethical justification. Incomplete portrayals of supporting evidence hamper the ability of individuals or authorities to evaluate the trials’ risks, benefits, and scientific merit.
To assess the prevalence of such omissions, researchers accessed the ClinicalTrials.gov registry and evaluated 101 randomly chosen clinical trials. Among those where there was at least one previous trial testing the same drug in the same disease, 30% of industry-sponsored trials and 20% of non-industry-funded trials failed to cite related studies. “Clinical trial protocols undercite easily accessible, relevant trials and do not document systematic searches for relevant clinical trials,” the authors wrote.
“Numerous studies suggest that some clinical trials are pursued despite their clinical hypotheses having been resolved prior to study launch,” write the authors. “Failure to provide a complete and impartial account of prior and ongoing research in study protocols may enable clinical research that fails to inform clinical practice.”
The data underpinning a controversial study of the use as vitamin C as a sepsis treatment may in fact be fraudulent, according to an analysis by an Australian physician and statistician, reports MedPage Today.
PhD student Kyle Sheldrick, MBBS, alleges that the pre- and post- comparison groups involved in the 94-patient study were too similar to be realistic.
In an interview with MedPage Today, Sheldrick said the case is “extreme”, stating that “This is probably the most obviously fake data I have seen. … These groups are more similar than would be probable.”
The paper, led by Paul Marik, MD – who led another COVID protocol study that has since been retracted – has been the subject of much debate in the intensive care community since it was published in 2017. The so-called HAT protocol was a simple regimen of hydrocortisone, ascorbic acid (vitamin C), and thiamine which could have saved many lives easily if it indeed worked. Obviously, there was much excitement worldwide about the significance of the findings – but not all were convinced.
“The effect size seemed just impossible,” said Nick Mark, MD, an ICU physician at Swedish Medical Center. “It seemed too good to be true.”
The trial was followed by larger studies, and so far none have shown shown a similar reduction in mortality, raising suspicions even further, Dr Mark said. With Sheldrick’s analysis, the penny dropped: “This was under our noses for 5 years,” Mark said. “This isn’t just a mistake. We know things can be done unethically, but to actually fake it? That it’s not just flawed, but perhaps actually fraudulent?”
Sheldrick told MedPage Today the key problem with the Marik paper is “probably the most common sign of fraud that we see, which is overly similar groups at baseline.” That is, people tend to fake data which do not vary enough from the average.
Sheldrick said he first looked at the study methods, which noted a pre- and post- comparison design, rather than a randomised or matched case-control design. With such a design, one would expect a more random distribution of baseline characteristics, but that wasn’t the case for the Marik paper, he said.
A further analysis with Fisher’s test showed that most P-values were 1, meaning they were distributed perfectly evenly across two time periods – and only one fell below 0.5. Instead, an even spread should be expected with an overall value of 0.5.
Sheldrick sent his findings to the journal CHEST and to Marik’s former employer Sentara Norfolk General Hospital, but had not heard back from either.
While Sentara Norfolk General Hospital did not respond to comment, and the journal CHEST could not confirm whether an investigation was underway but that it did take ethical concerns very seriously.
A spokesperson for Dr Marik emailed a statement to MedPage Today, claiming that the conclusions had been validated in several meta-analyses, and recommended the source examine “this and other research on the data before making false allegations on social media. Such claims are harmful and do not add to the public discourse.”
This wouldn’t be the first time concerns have been raised about data in a paper that Dr Marik co-authored. In November 2021, the Journal of Intensive Care Medicine (JICM) retracted an article by Marik and others on their MATH+ protocol for COVID. The retraction followed a communication that raised concerns about the accuracy of COVID mortality data from the hospital used in the article.
“It seems a bit improbable for someone to discover two miracle cures in three years,” Dr Mark commented to MedPage Today.
Dr Mark noted that the 2017 paper is widely cited, and even if the intervention was not directly harmful, the resources invested in subsequent large, high-quality trials of vitamin C and sepsis could have been better spent.
“While I’m really glad we did high-quality studies and had brilliant people working on this, it’s kind of a shame,” he said. “Instead of studying vitamin C based on a faulty premise, we could have spent our efforts elsewhere.”
Medical experts who were under the impression they were contracted by the Road Accident Fund (RAF) to provide expert medical opinions, have written to acting chief justice Raymond Zondo to withdraw their completed opinions that have not yet been used in court because the RAF refuses to pay them or has charged penalties to reduce the amounts owed.
These qualified specialists provided expert medico-legal services, such as consultations and injury assessments, preparation of expert witness reports, attended expert witness meetings, prepared joint minutes of expert meetings, and presented expert evidence in court for the former panel of attorneys rendering this service for the RAF.
The experts say they have had enough of struggling for payments from the RAF and they state in the letter that their work “may not and should not be used as evidence in any matter” in the future because it is said to be unauthorised and not paid for. In effect, this means that RAF cases can no longer progress until these experts have been paid or until new medical expert opinions are obtained.
The RAF only recently informed all medical experts appointed by its former panel of attorneys that they were not authorised to perform these services which were conducted since 2015 and will therefore not be paid.
Mariëtte Minnie, director of MMB Made Easy, which handles medical accounts of medical-legal service providers says accounts she deals with have a total outstanding value of R63.5 million, with some accounts dating back as far as 2015. The biggest outstanding balance among her clients is R10,7 million the RAF owes to one neurosurgeon.
As a result of ongoing non-payment, some experts have shut down and sold their houses and cars due to huge overdrafts and VAT owed to SARS for opinions for which the RAF has not yet paid.
Minnie adds, “The RAF has stolen thousands of medico-legal reports from hundreds of experts which they do not intend to pay for.”
Medical experts have always been instructed by the panel attorneys as RAF representatives, but the RAF never renewed its expert contracts in time. The RAF then terminated the services of the panel of attorneys who had to obtain RAF authorisation for the experts but still asked experts to continue assessing claimants to avoid delays and send their reports directly to the RAF.
Minnie says that invoices for work done in previous years are met with delaying tactics and even denial of payment. “The RAF now implements terms of the service level agreement with the experts to fine them with 5% for every day that their reports are submitted after the due date although submission of reports is subject to factors such as obtaining necessary documentation to finalise the report.”
The RAF has also instituted steps to eradicate “irregular expenditure”, suggesting that experts assessed claimants and wrote reports without authorisation although the RAF failed to implement adequate systems to instruct and remunerate them.
Minnie comments, “The RAF is shambolic and has been unable to operate ethically or effectively since 2015. We will also be bringing this matter to the attention of the Minister of Transport, the Special Investigations Unit, the Public Protector, the National Prosecuting Authority and the National Treasury. New leadership is required to turn around the RAF.”
The CGE cited an article published in Obstetrics and Gynaecology which found that women receiving Pfizer-BioNTech, Moderna or J&J COVID vaccines, vaccine administration was associated with less than a one-day change in cycle length for both vaccine-dose cycles compared with pre-vaccine cycles. The article concluded that clinically meaningful change in menstrual cycle duration associated with COVID vaccination was found.
The CGE used this study as justification, cautioning businesses and institutions against mandatory vaccination and recommended against sanctions for employees who chose to remain vaccinated.
The signatories expressed their concern at the contents of the statement which is at odds with the scientific understanding of COVID vaccinations, a concern which is compounded by the “enormous influence” of the GCE.
They accept that the vaccine mandates are subject to legal scrutiny, but take issue with the commission “trying to bolster its argument by wrongly insinuating that COVID vaccination has the potential to harm women’s health.”
They also point out that the commission seems to disregard the much greater risks to women and their unborn babies of COVID infection, while misinterpreting evidence on minor menstrual cycle lengthening. This creates fear and confusion in vaccinated women, and may increase vaccine hesitancy.
“It fails to appreciate that one in six unvaccinated pregnant women admitted to hospital in South Africa with COVID infection requires mechanical ventilation, and one in 16 has a fatal outcome,” the signatories stated.
They noted that COVID vaccination provides upwards of 80% protection against severe disease, hospitalisation and death.
The evidence is “indisputable” that COVID vaccination is safe, does not negatively affect women’s bodies and saves the lives of women, they stress. Statements to the contrary are strongly repudiated.
“We are of the view that the CGE, like all state institutions, medical and scientific bodies, social partners and civil society formations working in the fields of women’s rights, empowerment and equality, should urge women to get vaccinated and advance and defend their rights to all relevant information about and access to vaccination.”
The signatories call on the CGE to withdraw its 16 January statement and to share with it scientific facts on COVID vaccination and women’s health.
The former Gauteng deputy director-general for mental health services, Hannah Jacobus, has the process to move Life Esidimeni patients was rushed. She was being cross-examined by the State’s Advocate Willem Pienaar.
The much-delayed inquest meant to determine any criminal liability for the deaths of 144 mental health patients in the 2016 Life Esidimeni disaster continued virtually on Monday.
Jacobus’ role was in downscaling of patients at Life Esidimeni for cost savings, and says there was no indication of it closing at the time. When its closure was announced, these downscaling plans were not implemented and there was no timeframe given for when patients were to move out.
The former deputy DG admitted to writing false licences for NGOs, under pressure from then head of Gauteng mental health services, Dr Makgoba Manamelashe. However, Jacobus maintained that while she assessed their suitability, she ultimately did not issue any licences.
Dr Manamela signed licences authorising inexperienced‚ underfunded‚ poorly equipped NGOs to look after patients with profound mental illnesses.
After the Gauteng health department terminated the contract with Life Esidimeni, NGOs were used to care for the 1712 patients.
Dr Manamela admitted to Solidarity advocate Dirk Groenewald that the NGOs to which she gave authority did not comply with the legal requirements. In 2017, it was found that patients were transferred to NGOs that had been issued “unlawful and knowingly fraudulent” licences.
Many NGOs were subsequently found to be entirely unprepared for the patients they received, some lacking sufficient food, water, medication, staff or blankets. According to Jacobus, the process have only been completed by 2020 according to the downscaling schedule.
“From December 2015 to the end of March 2016 [is not] a sufficient period to determine and appoint suitable NGOs to receive mental healthcare [patients]. No NGOs were ready by the end of March. We needed more time,” she said.
A liver surgeon in the UK who branded his initials on the livers of two patients has been struck off the medical register.
The incidents, which occurred in 2013, involved the surgeon using an argon beam machine to write his initials “SB” on the livers of two anaesthetised patients while working at Birmingham’s Queen Elizabeth Hospital. In liver transplants, the argon beams are normally used for cauterisation and to highlight areas to work on.
His actions came to light when 4cm initials were discovered by another surgeonon an organ that had been transplanted by Bramhall and failed about a week after the operation. Pictures of the branding were taken with a mobile phone.
Bramhall tendered his resignation at the Birmingham hospital in 2014.
In a review of the case, the UK’s Medical Practitioners Tribunal Service (MPTS) said it was an “act borne out of a degree of professional arrogance”, adding that his actions “undermined” public trust in the medical profession.
In December 2017, Simon Bramhall, admitted two counts of assault by beating at Birmingham Crown Court and was fined £10 000 (R210 000). In December 2020 , he was suspended from the profession for at least five months, but a report from the latest tribunal on Monday said a review hearing on 4 June found his fitness to practise was no longer impaired by reason of his criminal convictions and his suspension lifted.
After an appeal from the General Medical Council (GMC), the sanction was quashed and then the case resubmitted to MPTS for its consideration.
On Monday, MPTS found Bramhall’s actions “breached” the trust between patient and doctor, and he was struck off.
The MPTS tribunal concluded that a suspension order would be “insufficient to protect the wider public interest” and said erasure from the medical register would be an “appropriate and proportionate sanction”.
A new opinion piece provides an exhaustive examination of the ethics of using hospital resources on unvaccinated-by-choice COVID patients with pneumonia, versus patients with other serious but slower illnesses.
In his article published online in the Annals of the American Thoracic Society, William F. Parker, MD, PhD, looked at cases in which hospitals delayed time-sensitive and medically necessary procedures for vaccinated adults when they were overwhelmed with unvaccinated patients who had severe, life-threatening COVID pneumonia and suggested an ethical framework for triaging these patients.
“These vaccinated patients are directly harmed when hospitals use all their resources to care for the many unvaccinated patients with COVID,” he wrote. “For example, delaying breast cancer surgery by just four weeks increases the relative risk of death from the disease by 8%.”
Dr Parker argues for a contingency care standard prioritising emergency life-support, regardless of vaccination status, in order to save the most lives. “Simply rejecting the use of vaccination in prioritisation of medical resources without analysis ignores the very real tradeoffs at play during a pandemic. The pain and suffering of the vaccinated from deferred medical care require a deeper defense of caring for the unvaccinated.”
Eliminating double standards He stated: “Even though the vast majority of patients who develop life-threatening COVID pneumonia are unvaccinated, hospitals still have ethical obligations to expand capacity and focus operations on caring for them—even if it means making vaccinated patients wait for important but less urgent care like cancer and heart surgeries.”
“If tertiary care centers turn inward and stop taking transfers of COVID patients from overwhelmed community hospitals, this will result in de facto triage in favor of lower benefit care and cause systematic harm to both the vaccinated and unvaccinated in vulnerable communities,” he adds. “Hospitals must justify their nonprofit status by accepting transfers and prioritizing life-saving care during a pandemic surge.”
He cited the example of a surge in Los Angeles, when the public health department had to issue an order forcing elite hospitals to stop doing financially lucrative elective procedures and accept patient transfers from community hospitals with ICUs overwhelmed by COVID.
Reciprocity and proportionality The principle of reciprocity supports a possible tiebreaker role for vaccination status when two patients have equivalent survival benefit from a scarce health care resource. However, a universal exclusion of the unvaccinated from life support during a pandemic surge fails the test of proportionality for reciprocity, according to Dr Parker.
Reciprocity is rewarding one positive action with another. One example of this principle is giving vaccinated people access to sporting or entertainment events that are off limits to the unvaccinated (even if negative for COVID). Proportionality is the principle that ‘payback’ should be proportional to the magnitude of the act. For example, living kidney donors get moved way up the waitlist- the equivalent of four years of waiting time on dialysis. This satisfies the proportionality principle.
Dr Parker points out that while the increased relative risk of death of 8% from deferring breast cancer surgery is awful, the absolute increase in risk is only one per 100, and perhaps only one per 200 for a two-week deferral. “After the surge is over, the hospital can catch up on deferred elective surgeries,” he wrote. “The harm from a coronary artery bypass or cancer surgery delayed two weeks is real, but tiny in comparison to certain death from denying life support for respiratory failure.”
He concluded that: “There is a defensible role for vaccination status in triage as a limited tiebreaker, not as a categorical exclusion, but only in the context of a well-defined and transparent triage algorithm. Despite the enormous financial pressure to do otherwise, elite academic centres are obligated to prioritise life support for emergency conditions to save as many lives as possible during COVID surges.”
Nine of South Africa’s leading healthcare organisations have joined together in urging the Government to begin a review of culpable homicide law and its application in a healthcare setting.
In a letter to the Minister of Justice and Correctional Services, Hon Ronald Lamola, the coalition said there is a very low threshold in South African law for blameworthiness when a patient dies while under medical care, which has resulted in errors of judgement in complex healthcare environments being criminalised, and healthcare professionals being convicted regardless of their intent.
The joint letter calls for the review to be carried out by the South Africa Law Reform Commission, due to the complexity of criminal law in a healthcare setting and the importance of achieving a long-term solution for healthcare professionals and patients alike.
The letter says: “It is hard to see who benefits from the current system. As well as families losing a loved one through tragic circumstances, doctors risk losing their career and liberty, and the fear of criminal charges also has a negative knock-on effect on patient care. The current system stands in the way of patients receiving an early apology and a full explanation of events, and thereby denies closure.
In a recent surveyof 500 doctors, 88% are worried about investigations after an adverse patient outcome, and 90% think the prospect of criminal investigation affects their mental health. Due to the prospect of criminal investigation means nearly half of all doctors in South Africa have considered leaving the profession. The letter further notes that 4 in 5 doctors surveyed think the criminal justice system in South Africa has an inadequate understanding of medical practice.
Pointing out the need for a “long-term solution”, they write: “Healthcare professionals need to be held accountable, however, criminalising errors of judgement – particularly in this fast moving and complex healthcare environment – seems unreasonably severe. Criminalisation in the absence of any clear intention to cause harm is overly punitive, leaving healthcare professionals vulnerable to criminal charges. Lessons can be learned from other jurisdictions – for example, in Scotland, where charges are only brought against doctors if an act is proved to be intentional, reckless, or grossly careless.
“Our organisations are committed to the highest level of safety for all patients in South Africa. This will however require replacing the current culture of blame and fear with one of learning, where healthcare professionals feel able to apologise and learn from mistakes, which will help to reduce the number of errors and thus enable progress on improving patient safety. When healthcare professionals are allowed and supported to learn from mistakes, lessons are learnt, and patients are better protected in the future.
Highlighting the complexity of these matters, “Patients and clinicians want the same thing, for those in need to receive the best care,” the letter concludes.
The letter was signed by Medical Protection Society, Association of Surgeons of South Africa, Federation of South Africa Surgeons, Radiological Society of South Africa, South African Medical Association, South African Medico-Legal Association, South African Private Practitioners Forum, South African Society of Anaesthesiologists and South African Society of Obstetricians and Gynaecologists.
A study published by the BMJshines a light on an extensive network of financial and non-financial ties maintained by the medical product industry with all major healthcare parties and activities.
The researchers called for greater oversight and transparency for this largely opaque and unregulated network, “to shield patient care from commercial influence and to preserve public trust in healthcare.” While the medical product industry is a critical partner in advancing healthcare, especially with the development of new tests and therapies, they have financial returns to shareholders as their main objective.
In a landmark 2009 report [PDF], the Institute of Medicine described a multifaceted healthcare ecosystem rife with industry influence.
To date most research into medical industry conflict of interests have focused on a single party (eg. healthcare professionals, hospitals, or journals) or a single activity (eg. research, education, or clinical care). Thus, the full extent of industry ties across the healthcare ecosystem remains uncertain.
To address this gap, a team of US researchers set out to identify all known ties between the medical product industry and the healthcare ecosystem.
They searched the medical literature for evidence of ties between pharmaceutical, medical device, and biotechnology companies and parties (including hospitals, prescribers and professional societies) and activities (including research, health professional education and guideline development) in the healthcare ecosystem.
The researchers drew in data in 538 articles from 37 countries, along with expert input, to create a map depicting these ties. These ties were then verified, catalogued, and characterised to ascertain types of industry ties (financial, non-financial), applicable policies on conflict of interests, and publicly available data sources.
The results show an extensive network of medical product industry ties – often unregulated and non-transparent – to all major activities and parties in the healthcare ecosystem.
Key activities include research, healthcare education, guideline development, formulary selection (prescription drugs that are covered by a health plan or stocked by a healthcare facility), and clinical care.
Parties include non-profit entities (eg foundations), the healthcare profession, the market supply chain (eg payers, purchasing and distribution agents), and government.
For example, the researchers describe how opioid manufacturers provided funding and other assets to prescribers, patients, public officials, advocacy organisations, and other healthcare parties, who, in turn, pressured regulators and public health agencies to stifle opioid related guidelines and regulations.
They also warned that harms from industry promoted products remain unexplored. All party types were found to have financial ties to medical product companies, with only payers and distribution agents lacking additional, non-financial ties.
They also show that policies for conflict of interests exist for some financial and a few non-financial ties, but publicly available data sources seldom describe or quantify these ties.
The researchers acknowledge that their findings are limited to known or documented industry ties, and that some data might have been missed. However, they say their strategy of systematic, duplicative searching and feedback from an international panel of experts is unlikely to have missed common or important ties.
In light of this, they conclude: “An extensive network of medical product industry ties to activities and parties exists in the healthcare ecosystem. Policies for conflict of interests and publicly available data are lacking, suggesting that enhanced oversight and transparency are needed to protect patients from commercial influence and to ensure public trust.”
A study by the Mayo Clinic found that most healthcare workers experience violence in emergency departments (EDs), but they seldomly report it to anyone.
Over six months prior to being surveyed, 72% of healthcare workers and other ED staff said they had personally experienced violence (71% verbal abuse and 31% physical assault), Sarayna McGuire, MD, chief resident of Mayo Emergency Medicine in Rochester, Minnesota, reported in a series of three studies at the American College of Emergency Physicians annual meeting.
Nurses and clinicians, along with security personnel, bore the brunt of the attacks: 94% of nurses and 90% of clinicians reported experiencing verbal abuse, and 54% of nurses and 36% of clinicians reported instances of physical assault.
“The whole team is impacted by workplace violence,” Dr McGuire said to MedPage Today. “Even people coming in to draw blood are being assaulted physically and verbally abused.”
Despite this prevalent violence and 58% reporting at least moderate awareness of reporting policies, 77% of all respondents said they never or rarely report violence, while only 10% said they often or always do.
A possible explanation could be that only 7% of non-security staff said they were “extremely familiar” with the procedures. And when participants were asked why ED abuse is not usually reported, the top four reasons given were:
No physical injury was sustained (53% of respondents)
“It comes with the job” (47%)
Staff are too busy (47%)
Reporting is inconvenient (41%)
The violence is not without consequences; 18% of respondents said they are considering leaving their position due to the violence, and 48% said violence has changed the way they view or interact with patients.
Men and more experienced staff reported feeling significantly better prepared compared with women. When asked which factors staff thought were most responsible for the violence, the following feature in at least 70% of responses: alcohol, illicit drugs, and significant mental illness.
A total of 86% of respondents said they felt at least moderately prepared to handle verbal abuse, while 68% said they felt prepared to handle physical assault.
“Everyone’s feeling right now that violence has increased in healthcare [during the pandemic], and our data have showed that,” Dr McGuire said. “How is this sustainable? …There is a critical issue in healthcare.”
She added that since reporting of violence is so low, true exposure to violence is probably much higher than the study found.
Study co-author Casey M. Clements, MD, PhD, also of Mayo Emergency Medicine, added that “we know this isn’t isolated to emergency departments.”
He explained that while the study encompassed the pandemic era, violence “has been a problem for some time in healthcare” – violence is a major threat to the healthcare workforce, Dr Clements said. He added that another problem is that physicians typically do not receive any training in de-escalation — “we learn this on the job.”
For the study, the researchers sent an anonymous survey to ED staff at 20 EDs. Also included were social workers, management, and security staff. Women made up 73% of the 833 respondents. Nursing staff (31%) made up the largest medical discipline, and 16% were clinicians.
Dr McGuire suggested that a centralised reporting system would help augment reporting of violence.
“We need to change the mindset that it’s anybody’s job to be assaulted at work,” Dr Clements said. “We cannot go on having our emergency department workers being abused and assaulted on a daily basis.”
