Tag: clinical trials

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UK Launches World’s First Trial of Lung Cancer Vaccine

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Image of a lung lobe showing cells expressing the basal cell marker Krt5 spreading. Credit: UCL.

In the UK, people at high risk of lung cancer will soon be able to receive the first ever experimental vaccine designed to prevent the disease, in a world-first clinical trial led by researchers at UCL and the University of Oxford.

The research team has been awarded up to £2.06 million from Cancer Research UK, supported by the CRIS Cancer Foundation, to run a clinical trial of LungVax over the next four years.

This phase I trial will investigate the best dose of LungVax to give to people at high risk of lung cancer, as well as looking for any potential side-effects from different doses of the vaccine.

The trial is expected to begin in summer 2026, subject to regulatory approvals.

Professor Mariam Jamal-Hanjani, co-founder and lead for the LungVax clinical trials, from UCL Cancer Institute, UCLH and the Francis Crick Institute, said: “Fewer than 10% of people with lung cancer survive their disease for 10 years or more. That must change, and that change will come from targeting lung cancer at the earliest stages.

“The LungVax clinical trial is the crucial first step in bringing this vaccine to people at the highest risk of the disease. We will be looking carefully at how people respond to the vaccine, how easy it is to deliver, and who might benefit from it most in the future.

“Preventative vaccines will not replace stopping smoking as the best way to reduce the risk of lung cancer. But they could offer a viable route to preventing some cancers from emerging in the first place.”

Lung cancer cells are different from normal cells. They have ‘red flag’ proteins made by cancer-causing mutations within their DNA. These are called neoantigens and tumour associated antigens and appear on the surface of cells at a very early stage of lung cancer formation.

The LungVax vaccine carries a series of genetic instructions which train the immune system to recognise these tumour antigens on the surface of abnormal lung cells. In trialling the vaccine, the aim is to get the immune system to recognise these early abnormal cells, and kill them before they start to become cancer. The vaccine uses technology developed by the University of Oxford during the COVID-19 pandemic to deliver these instructions to the immune system.

Professor Sarah Blagden, co-founder of the LungVax project from the University of Oxford, said: “Lung cancer is lethal and blights far too many lives. Survival has been stubbornly poor for decades. LungVax is our chance to do something to actively prevent this disease.

“Years of research into the biology of cancer, understanding the fundamental changes which occur in the very earliest stages of the disease, will now be put to the test. This funding means that, for the first time, we hope that people will be able to receive LungVax in clinical trials from next year.” 

To find out how safe and effective the vaccine is, the trial will initially focus on people who have been diagnosed with early-stage lung cancer and have had it successfully removed but are at risk of it returning. The vaccine will also be tested in people who are undergoing lung cancer screening as part of the NHS Lung Cancer Screening Programme in England.

If the trial delivers promising results, the vaccine could then be scaled up to larger trials for people at risk of lung cancer.

There are around 48 500 cases of lung cancer every year in the UK. Around 72% of lung cancers are caused by smoking, which is the biggest preventable cause of cancer worldwide.

Graeme Dickie, 55, from Kilbarchan in Renfrewshire, is helping the scientists prepare for the LungVax clinical trial. In 2013, aged 42, he was diagnosed with stage II lung cancer. By 2017, it had progressed to stage IV. He has never smoked. Over the years, he’s undergone surgery to remove part of his left lung, and more than 80 rounds of chemotherapy. When those treatments stopped working, Graeme began a new targeted treatment drug, mobocertinib, that he continues with today.

Graeme said: “I am proof that research saves lives. I have been able to enjoy many more happy years with my family thanks to scientists working hard, year after year, to bring new tests and treatments.

“For me, research is vital. I won’t be able to benefit directly from LungVax personally, but I know that my story will help others to access better interventions at an early stage.”

  • Image of a lung lobe showing cells expressing the basal cell marker Krt5 spreading. Credit: UCL.

Source: University College London

Categories : Medical Research & Technology Respiratory DiseasesTags :

No Benefits Seen from Conservative Oxygen in the ICU

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A UK trial involving 16 500 mechanically ventilated intensive care unit (ICU) patients found no 90-day survival benefit for conservative supplemental oxygen over usual oxygen therapy. Nevertheless, the study, published in JAMA, did demonstrate the accuracy and cost-effectiveness of conducting a large trial with a simple intervention.

Oxygen is one of the most commonly administered treatments to patients in ICUs, but liberal oxygen therapy to avoid the risks of hypoxaemia may lead to harm, so finding the right level could optimise outcomes. Trials to date have shown mixed results.

For COVID patients admitted to the ICU with severe hypoxaemia, survival without life support was extended with conservative oxygen therapy. In a paediatric ICU study, conservative oxygen therapy resulted in a reduction in a composite of organ support at 30 days or death. A meta-analysis of 13 trials showed no differences between liberal and conservative oxygen therapy.

Even with just a small difference in survival benefit, with tens of millions of patients mechanically ventilated in the ICU would still mean significant numbers of lives saved. Other tests of new drugs and procedures in the ICU are hampered by high cost, as Seitz et al. noted in an accompanying editorial, so this sort of trial comparing two approaches to a common therapy is much more affordable.

The UK Intensive Care Unit Randomised Trial Comparing Two Approaches to Oxygen Therapy (UK-ROX) trial was initiated to determine if there was a difference between conservative and usual oxygen therapy.

The trial randomised 16 500 patients across 97 ICUs in the UK to either conservative oxygen therapy or usual oxygen therapy, in adults receiving mechanical ventilation and supplemental oxygen in the ICU. The primary outcome was mortality at 90 days. Conservative oxygen therapy targeted a peripheral oxygen saturation (Spo2) of 90% (range, 88%-92%), while usual oxygen therapy was at the discretion of the treating clinician.

Patients were early in mechanical ventilation (median, 5 hours), were severely ill (median predicted mortality risk, 35%), had a range of critical illnesses (eg, > 5000 patients with sepsis and > 1500 patients with hypoxic-ischaemic encephalopathy) and with significant hypoxaemia (eg, > 11 000 patients with a Pao2:Fio2 ratio, consistent with acute respiratory distress syndrome). Obtaining informed consent from the patients was, of course, largely not feasible, so this requirement was waived for the study.

Exposure to supplemental oxygen was 29% lower for those in the conservative oxygen therapy group compared with the usual oxygen therapy group. Of the patients randomised to conservative oxygen therapy, 35.4% died by 90 days compared with 34.9% of patients receiving usual oxygen therapy.

No differences were seen for secondary outcomes, including ICU stay, days free of life support and mortality at various time points. No interactions for confirmed or suspected COVID, ethnicity or other illnesses were observed.

Post hoc analysis showed weak evidence of increased harm from conservative oxygen therapy among the first 10 patients in each site but no difference for the random enhanced data collection sample compared with standard data collection.

Seitz et al. pointed out that the high level of adherence to the conservative target resulted in a mean oxygen saturation of 93.3%, versus 95.1% for usual care. The differences in oxygen saturation (1.9%) and Fio2 (0.04) between the trial groups in UK-ROX were about half the magnitude of some prior trials, due to not aiming for widely separated targets, and usual care varies considerably depending on location and clinical considerations.

Therefore, the researchers concluded that the findings do not support an approach of reducing oxygen exposure by targeting an Spo2 of 90% in mechanically ventilated adults receiving oxygen in the ICU. They suggest that future research may involve using AI to determine specific situations where conservative or liberal oxygen therapy may have beneficial outcomes.

References:

Martin DS, Gould DW, Shahid T, et al. Conservative Oxygen Therapy in Mechanically Ventilated Critically Ill Adult Patients: The UK-ROX Randomized Clinical Trial. JAMA. 2025;334(5):398–408. doi:10.1001/jama.2025.9663

Seitz KP, Casey JD, Semler MW. Patient, Treatment, Outcome—Large Simple Trials of Common Therapies. JAMA. 2025;334(5):395–397. doi:10.1001/jama.2025.9657

Categories : Mental HealthTags :

Is It Really ADHD? Serious Flaws in Trials With Adult ADHD Patients

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Millions of adults around the world are diagnosed with ADHD every year, and there is a great need for research in the field. Yet much clinical research on adult ADHD suffers from serious methodological shortcomings that make it difficult to use the results in practice, researchers from the University of Copenhagen and the University of Sao Paulo show in a new study.

Originally developed for children, the diagnosis of ADHD is often difficult to make in adults. This is partly because the diagnostic criteria are based on behaviour in children. When diagnosing adults, however, these criteria are often based on adults’ subjective experiences, eg, of having difficulty concentrating or being very impulsive.

“The rising number of adults diagnosed with ADHD raises important questions about diagnostic validity – especially since many were never identified in childhood and are now seeking help, sometimes prompted by ADHD content on social media. That made us curious: how have randomised controlled trials on ADHD dealt with this diagnostic challenge?” explains Dr Igor Studart, who is first author of the study published in European Psychiatry.

Moreover, ADHD shares its symptoms with a number of other mental disorders such as depression, schizophrenia, and bipolar disorder, making it crucial to exclude these disorders when diagnosing ADHD. This requires a thorough diagnostic assessment by an experienced psychologist or psychiatrist.

But it is not always the case that such a thorough assessment is made. The study now shows that even psychiatric research into ADHD often neglects this fundamental work.

“We have examined how 292 of the most credible studies in evidence-based medicine – the so-called randomised controlled trials – diagnosed their adult subjects,” says Professor of Psychiatry and Consultant Psychiatrist Julie Nordgaard, who conducted the study together with Associate Professor and Senior Researcher Mads Gram Henriksen and Dr Igor Studart.

She continues:

“We conclude that half of the studies did not ensure a broad and thorough diagnostic assessment of the patients before the trial to rule out other disorders. This means that they can’t actually know, if their subjects have other mental disorders such as depression or schizophrenia. And that’s not all. More than half of the studies included subjects, who have also been diagnosed with other mental disorders, making the diagnosis even more difficult to allocate”, Julie Nordgaard explains.

According to the researchers, these methodological shortcomings are problematic, because they imply that it is impossible to know which disorders and symptoms the treatment investigated in these trials potentially had an effect on.

“This makes the research results from many of these clinical trials difficult to utilise. Yet, the results of randomised controlled trials are considered particularly trustworthy, and they may inform the guidelines we use to treat adult ADHD patients, even though the results from many of these trials should be assessed very carefully,” says Mads Gram Henriksen.

A need for consistent and robust diagnoses

According to the researchers, one of the problems with the diagnostic assessment in many of the clinical trials is that it seems to have been carried out by people who are not trained to do so. And often with methods that are not thorough enough.

“In 61% of the studies, they do not state who diagnosed the subjects. In only 35% of the studies, it is stated that a psychiatrist or psychologist made the diagnosis. But diagnostic assessment should always be performed by an experienced professional with the necessary training to ensure that the diagnosis is made correctly, and this should be stated in the studies’ method section,” explains Mads Gram Henriksen.

In some cases, the assessment and thus the diagnosis was made by the subject themselves, and in one particularly egregious case, it was done with the help of a computer, the researchers explain.

“In psychiatry, we really need that all diagnoses, not just ADHD, are made with the same uniform criteria and by trained professionals. Otherwise, we cannot rely on the results or compare them across studies,” says Julie Nordgaard and concludes:

“Especially in a situation where a diagnosis such as ADHD in adults is increasing, we need to be very thorough and have a solid foundation. Otherwise, we risk too many people getting a wrong diagnosis and not being able to give them the most effective treatment. Or they risk receiving unnecessary treatment that causes side-effects.”

Source: University of Copenhagen

Categories : Cardiovascular DiseaseTags :

BMJ Finds Inaccuracies in Key Studies for AstraZeneca’s Blockbuster Heart Drug Ticagrelor

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Investigation finds evidence of serious misreporting, raising fresh doubts over the approval and decade long use of ticagrelor

Photo by National Cancer Institute on Unsplash

In a follow up investigation into the multibillion dollar drug ticagrelor, The BMJ has uncovered fresh concerns, this time in key platelet studies used in its FDA approval.

For more than a decade, ticagrelor (Brilinta in the US and Brilique in Europe) has been recommended for patients with acute coronary syndrome – a range of conditions related to sudden reduced blood flow to the heart.

Last December, an investigation by The BMJ found serious data integrity problems in the landmark clinical trial (PLATO) that was used to gain worldwide approval for ticagrelor, calling into question the drug’s advantage over cheaper rivals.

Now, as generic versions of the drug prepare to launch this year, The BMJ has expanded its investigation, looking at two key platelet studies that AstraZeneca claimed explained ticagrelor’s ability to treat acute coronary syndrome successfully.

It finds that the “primary endpoint” results (the trial’s key measurement) for both clinical trials were inaccurately reported in the leading cardiology journal Circulation, and reveals that more than 60 of 282 readings from platelet machines used in the trials were not present in US Food and Drug Administration (FDA) datasets.

What’s more, one active trial investigator never became a study author, while one author told The BMJ he was not involved in the trial, and most investigators, including the principal investigator, were unreachable or declined to be interviewed.

Victor Serebruany, an adjunct faculty member at Johns Hopkins University and ticagrelor’s most renowned critic, told The BMJ that “there are episodes of skyrocketing rebound and profound platelet inhibition after ticagrelor making patients prone to thrombosis or bleeding. If doctors had known what happened in these trials, they would never have started using ticagrelor.”

Circulation and AstraZeneca did not respond to a request for comment.

Serebruany added: “It’s been obvious for years that there is something wrong with the data. That the FDA’s leadership could look past all these problems—on top of the many problems their own reviewers identified and are now being discovered by The BMJ—is unconscionable. We all need to know how and why that happened.”

Source: BMJ

Categories : Healthcare Politics and Regulations HIVTags :

SA Health Research Facing Catastrophic Financing Cuts

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Professor Ntobeko Ntusi is the president and CEO of the South African Medical Research Council. (Photo: SAMRC)

By Catherine Tomlinson

Cuts to United States funding of health research could have “catastrophic” consequences, says Professor Ntobeko Ntusi, who is at the helm of the country’s primary health research funder. He says the South African Medical Research Council is “heavily exposed” to the cuts, with around 28% of its budget coming from US federal agencies.

After an unprecedented two weeks of aid cuts by the United States government that left HIV programmes and research efforts across the world reeling, the Trump administration took the drastic step of freezing aid to South Africa in an executive order on 7 February.

The order – which is a directive to the executive branch of the US government and holds the weight of law – was issued to respond to what the White House called “egregious actions” by South Africa. It specifically points to the Expropriation Act and the country’s accusation of genocide against Israel at the International Court of Justice as the primary reasons for the funding freeze.

While there are some limited wavers and exceptions to the cuts, Spotlight understands that these have so far been poorly communicated and many HIV services remain in limbo.

The funding cuts, following an earlier executive order issued on 20 January,  are interrupting critical health research underway across South Africa and will ultimately undermine global efforts to stop HIV and TB.

The US is a major source of financing for health research in South Africa. Many of the country’s research institutes, groups, and universities receive funding from the US through the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC), USAID, and the President’s Emergency Plan for Aids Relief (PEPFAR).

Over the past few weeks, these funding sources have come under siege by the Trump administration resulting in a gaping, and most likely insurmountable financing gap, for many health research endeavors in the country.

US spending accounts for just over half (55%) of all spending on global health research around the world. In 2022, the super power spent $5.4 billion on global health research, according to Impact Global Health –  an NPO that tracks health research spending.

While the US gives money to global health research through several different government departments and programmes, the largest source of funding for global health research is the NIH. The NIH contributed 65% of global financing for HIV research between 2007 and 2022, according to Impact Global Health and 34% of tuberculosis research financing in 2023, according to New York-based policy think tank, the Treatment Action Group.

South Africa has the biggest HIV epidemic in the world in absolute terms and is among the top 10 countries in terms of TB cases per capita.

Catastrophic consequences

“South Africa is the biggest recipient of NIH funding outside of the US”, Professor Ntobeko Ntusi, president and CEO of the South African Medical Research Council (SAMRC), told Spotlight. “[T]he consequences will be catastrophic if [funding] is stopped… for science that is important for the whole world,” he said.

South Africa plays a critical role in advancing HIV science, said Ntusi, adding that “many of the major trials that have advanced our understanding of both the effective strategies for HIV management, as well as understanding the mechanisms of disease emanated from South Africa”.

People in the US, for example, are now able to access long-acting HIV prevention shots, largely because of research that was conducted in South Africa and Uganda. Research conducted in South Africa has also been critical to validating new tuberculosis treatments that are currently the standard of care across the world.

Heavily exposed

Stop work orders were sent to research groups receiving USAID funding at the end of January. These stop work orders coupled with the halting of funding have already interrupted critical HIV research efforts, including efforts to develop new vaccines against HIV.

Ntusi said that the SAMRC is currently “heavily exposed” to the halting of grants from USAID and the CDC, with research programmes supported by USAID and the CDC already being stopped.

The SAMRC’s research on infectious diseases, gender-based violence, health systems strengthening, as well as disease burden monitoring are also affected by the funding cuts.

“In addition to support for HIV research, we have significant CDC grant funding in our burden of disease research unit, the research unit that publishes weekly statistics on morbidity and mortality in South Africa,” said Ntusi. “Our health systems research unit has a number of CDC grants which have been stopped [and] in our gender and health research unit we had a portfolio of CDC funding which also has been stopped.”

Along with programmes being impacted by the halting of USAID and CDC funding, Ntusi said there will also be major staffing ramifications at the SAMRC as well as at universities.

He said that if funding from the NIH is stopped “there would be huge fallout, we just wouldn’t be able to cover the hundreds of staff that are employed through the NIH granting process”.

The SAMRC’s combined annual income from US grants (NIH, CDC and USAID) is 28% of its total earnings (including both the disbursement from the SA government as well as all external contracts) for the 2025/2026 financial year, according to Ntusi. “So, this is substantial – effectively a third of our income is from US federal agencies,” he said.

Pivot away from infectious disease?

In addition to the executive order freezing funding to South Africa, it is unknown whether the NIH will remain a dominant funder of global health. Robert F. Kennedy Jr., the US health secretary nominee, has called for cutting to the NIH’s infectious disease research spending to focus more on chronic diseases.

Looking beyond health, Ntusi said the executive order halting aid to South Africa will be felt across a range of different development initiatives such as water and sanitation, and climate change.

Republished from Spotlight under a Creative Commons licence.

Read the original article.

Categories : HIVTags :

Trial Shows Twice-yearly Injection to be 99% Effective in HIV Prevention

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Photo by Miguel Á. Padriñán: https://www.pexels.com/photo/syringe-and-pills-on-blue-background-3936368/

For oral medications that prevent new HIV infection to be effective, the patient must take certain actions, including attending doctor’s visits every three months and – most importantly – consistency.

These daily oral antiretrovirals, more commonly referred to as PrEP (pre-exposure prophylaxis), such as Truvada®, are extremely effective at HIV prevention, but only if they are taken daily as directed. Truvada’s efficacy is greatly compromised when taken inconsistently.

However, results from a recent Gilead-funded clinical trial (Purpose-2) led by physicians at Emory University and Grady Health System indicate that a twice-yearly injection of Lenacapavir offers a 96% reduced risk of infection overall, making the injection significantly more effective than the daily oral PrEP. The findings were recently published in the New England Journal of Medicine.

“Seeing these high levels of efficacy – at almost 100% – in an injectable that people only have to take every six months is incredible,” says Colleen Kelley, MD, lead author of the study and professor in the School of Medicine at Emory University. “This is a considerable and profound advancement in medicine, especially for people whose circumstances don’t allow them to take a daily oral medication, and for those among populations disproportionately impacted by HIV.”  

In the randomised, double-blind, Phase III clinical trial comparing the efficacy of the two medications, 99% of the participants in the Lenacapavir group did not acquire an HIV infection. During the trial, only two participants in the Lenacapavir group, comprised of 2,179 people, acquired HIV. This compares to nine new HIV infections in the Truvada®group, which had 1,086 people. The trial showed that adherence to the injectable was higher than of the daily oral pill. 

Kelley adds that while PrEP is incredibly effective at preventing infection, part of what made the injection more effective in the clinical trial was the challenges associated with adherence to a daily oral pill.

“What we see over time is that about half of people who start taking daily oral PrEP stop within a year due to various factors,” says Kelley, referencing healthcare disparities in general. “Having an effective injectable that is only needed twice annually is very significant for people who have trouble accessing healthcare or staying adherent to daily, oral pills.”

The inclusion of racially, ethnically, and gender-diverse participants in the clinical trial was notable because it was representative of populations disproportionately impacted by HIV in real time. For example, the trial groups were comprised of cisgender men and gender-diverse people at 88 sites in Peru, Brazil, Argentina, Mexico, South Africa, Thailand, and the US.

According to the study, the same populations that are disproportionately impacted by HIV are the same populations that have limited access to PrEP – or may have difficulty consistently taking the oral antiretroviral medication – ultimately highlighting the need for more options. The study also indicates that more than half of the new HIV infections nationwide in 2022 were among cisgender gay men, and 70% of those were among Black or Hispanic individuals. 

Valeria Cantos, MD, associate professor in the School of Medicine at Emory University, physician at Grady Memorial Hospital, and the principal investigator for the clinical trial at the Grady research site, emphasized the importance of having trials that include populations truly representative of the patients that Grady serves.

“At Grady, our focus is on increased representation of underserved and vulnerable populations, acknowledging and addressing the distrust towards research held by some community members due to prior abuses or neglect of these populations by research institutions in the past,” Cantos says. “Grady is an established, trusted research site because of its commitment to equity.”

 At the Grady clinical trial site, medical materials were available in Spanish, and bilingual staff members recruited and enrolled trial participants who only spoke Spanish. Cantos also indicated that the site enrolled participants who are representative of the populations that would benefit the most from Lenacapavir. In addition to Grady, the Hope Clinic and Emory Midtown Hospital were among the 88 sites supporting the clinical trial. 

“We are not reaching everyone we need to reach with our current HIV prevention interventions, such as those who are disproportionately impacted by HIV and health care disparities,” says Kelley. “For people that are unable to take the daily oral pills, the injectable agents can really give incredible efficacy and be a game changer in helping them stay HIV negative.”

Since the Phase III clinical trial has been completed and submitted by the FDA for consideration, Kelley is hopeful that Lenacapavir may be approved by 2025 for commercial use.

Source: Emory Health Sciences

Categories : HospitalsTags :

Bridging the Gap: How Pragmatic Trials can Better Serve Healthcare Systems

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A new thought piece led by the Harvard Pilgrim Health Care Institute with collaborators from Duke University and Kaiser Permanente Washington Health Research Institute highlights the challenges facing healthcare researchers and decision makers in the quest to improve population health in a constantly evolving healthcare landscape. The authors offer strategies to enhance the effectiveness of pragmatic clinical trials and increase their impact on real-world healthcare settings.

The Viewpoint appears October 2 in JAMA.

Pragmatic clinical trials, designed to inform health care decision-makers about the comparative benefits, burdens, and risks of health interventions, have seen a significant increase in interest over the past decade. Since 2012, the NIH Pragmatic Trials Collaboratory has supported 32 such trials, addressing critical issues like suicide prevention, opioid prescribing, and infection control.

Pragmatic clinical trials are designed to bridge the gap between research and care, and we believe this bridge can be built even more efficiently.
– Richard Platt, MD, MSc

Pragmatic clinical trials compare treatments in everyday clinical settings, rather than under ideal conditions. However, the authors note that the adoption of trial findings by healthcare systems has been inconsistent.

“Our goal is to ensure that the findings from these trials are not only scientifically sound but also readily implementable in diverse healthcare settings,” says lead author Richard Platt, Harvard Medical School distinguished professor of population medicine at the Harvard Pilgrim Health Care Institute. “Pragmatic clinical trials are designed to bridge the gap between research and care, and we believe this bridge can be built even more efficiently.”

The authors identify key challenges and propose solutions to align trial goals with healthcare system needs, including:

  • Identifying relevant outcomes: Collaborate with healthcare leaders to determine the clinical or cost-saving outcomes that would motivate adoption.
  • Shortening trial duration: Designing trials to span 2-3 years to match the decision-making timelines of healthcare systems.
  • Conducting interim assessments: Utilizing interim analyses to provide timely information and potentially stop or modify trials early.
  • Considering costs: Understanding and planning for associated costs to ensuring interventions are sustainable post-trial.

“By accommodating the priorities of healthcare leaders and introducing adaptive trial designs, we can generate actionable evidence that truly improves patient care,” adds Dr Platt.

Source: Harvard Pilgrim Health Care Institute

Categories : Medical Research & TechnologyTags :

Researchers Attempted to Emulate a Clinical Trial Using Data from Real Patients

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The method can be used to explore treatment effects in people underrepresented in clinical trials

Researchers used real-world clinical data to attempt to emulate a randomised controlled trial testing the effectiveness of two blood thinners, apixaban and warfarin, to prevent stroke in patients with non-valvular atrial fibrillation. The study, led by Emma Maud Powell at the London School of Hygiene and Tropical Medicine, UK, and publishing August 29th in the open-access journal PLOS Medicine, provides a method to explore the effects of treatments in patients who are underrepresented or excluded from clinical trials.

Patients experiencing atrial fibrillation – a potentially dangerous medical condition in which the upper chambers of the heart beat irregularly – will often be prescribed blood thinners such as apixaban or warfarin to prevent a stroke. However, these treatment recommendations are based on results from randomized controlled trials, and it is unknown if they are applicable to populations of patients who were not included in the trial or present only in very low numbers.

In the new study, researchers used routinely collected health data from patients in the United Kingdom to attempt to emulate a previous randomized controlled trial that compared the effectiveness of apixaban and warfarin. They attempted to emulate the patient eligibility, selection and analysis approaches as the previous trial. They found that patients prescribed apixaban had similar outcomes to patients prescribed warfarin, but unlike the previous trial, they did not find that apixaban was superior. The researchers observed the differences in results may have been linked to higher quality of warfarin control, sub-optimal dosing of apixaban, and differences in the ethnicity of patients and use of concomitant medications compared with the clinical trial population.

Overall, the study established that using an existing randomised controlled trial (the reference trial) as a guide for the design of observational analysis of real patient data is an effective and valid way to estimate the treatment effects and risks of blood thinners given to patients with atrial fibrillation. The methods developed in this study can be used to investigate the effects of these medications in patient groups that are excluded from or underrepresented in these clinical trials, such as the elderly, those with multiple conditions and people with a higher risk of bleeding. This method can also help medical researchers to understand whether results from randomized controlled trials are transferable to “real-world” practices, and provides a framework that can be adapted to investigate treatment effects for other conditions.

The authors add, “Our study aimed to emulate a reference trial in oral anticoagulants in patients with atrial fibrillation using routinely collected UK healthcare data. Reference-trial informed design provides a framework for the study of treatment effects in patient groups excluded from or under-represented in trials.”

Provided by PLOS

Categories : CancerTags :

Study Finds no ‘Participation Effect’ Benefit for Patients in Cancer Trials

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Cancer patients who participate in clinical trials hoping for better outcomes fare no better than those who do not, when setting aside the new treatment’s effect, according to the results of a study published in the Journal of the American Medical Association. The analysis found that while overall, trials had a positive benefit, this effect diminished after accounting for various factors common to trial participants such as being younger. Evidence of publication bias was also uncovered.

Participation in a clinical trial may confer a survival benefit to cancer patients is known as a trial effect, and results from access to effective new therapies (the treatment effect), but it is also thought that a trial’s closer monitoring provides a distinct benefit as well (the participation effect). The treatment effect only applies if the treatment proves to be effective, while the participation effect should apply regardless of treatment effect. But the evidence for the participation effect has been conflicting. A pair of reviews, one conducted in 2001 and the other in 2004, found no evidence of a participation effect.

The researchers therefore sought to account for biases and confounding in differences between routine care patients and trial patients. A search was performed for studies comparing survival outcomes for the two groups between January 1 2000 and August 31 2022, which turned up 12 791 records. After screening for eligibility and duplicates, this yielded 39 studies (85 comparisons) for analysis. These comparisons involved haematologic (21%), breast (16%), lung (14%), central nervous system (7%), prostate (7%), and pancreatic cancers (5%), as well as melanoma (6%). The remaining 24% consisted of bladder, cervical, colorectal, oesophageal, gastric, head and neck, kidney, ovarian, and solid mix tumours. One-third of the comparisons involved advanced or metastatic cancer.

Initially, the meta-analysis revealed a statistically significant overall survival benefit for trial participants (HR [hazard ratio], 0.76) when all studies were pooled without regard to their design or quality. But in study subsets matching trial participants and routine care patients for eligibility criteria, the survival benefits diminished (HR, 0.85). Finally, the survival benefit disappeared when only high-quality studies were pooled (HR, 0.91). They also disappeared when estimates were adjusted for potential publication bias (HR, 0.94).

Further analysis (using funnel plots and Egger’s regression test) indicated there was a publication bias against studies which lacked a participation effect.

In an accompanying editorial, Wilson et al. note that the participation effect explains that, “Patients in trials are generally younger, fitter, have fewer comorbidities, and come from higher socioeconomic groups; this enrollment bias largely explains the participation effect. The implications of this finding are important for understanding how trials are often viewed in clinical practice. The participation effect is often used to promote the view that “a clinical trial is the best treatment option, ‘but this may be a false narrative.”

Corresponding author Jonathan Kimmelman, PhD concluded: “Our findings provide reassurance that inability to enroll in a cancer trial doesn’t disadvantage a patient, at least in terms of survival. Our findings can help patients (and physicians) focus their consent discussions on the most relevant and evidence-based benefits of trial participation: the prospects of advancing the care of future patients.”

Categories : Medical Research & TechnologyTags :

Systematic Biases on Race and Gender at Play in Clinical Trials

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Randomized controlled trials, or RCTs, are believed to be the best way to study the safety and efficacy of new treatments in clinical research. However, a recent study from Michigan State University found that people of colour and white women are significantly underrepresented in RCTs due to systematic biases. 

The study, published in the Journal of Ethnicity in Substance Abuse, reviewed 18 RCTs conducted over the last 15 years that tested treatments for post-traumatic stress and alcohol use disorder. The researchers found that despite women having double the rates of post-traumatic stress and alcohol use disorder than men, and people of colour having worse chronicity than white people, most participants were white (59.5%) and male (about 78%). 

“Because RCTs are the gold standard for treatment studies and drug trials, we rarely ask the important questions about their limitations and failings,” said Nicole Buchanan, co-author of the study and professor in MSU’s Department of Psychology. “For RCTs to meet their full potential, investigators need to fix barriers to inclusion. Increasing representation in RCTs is not simply an issue for equity, but it is also essential to enhancing the quality of our science and meeting the needs of the public that funds these studies through their hard-earned tax dollars.”

The researchers found that the design and implementation of the randomised controlled trials contributed to the lack of representation of people of colour and women. This happened because trials were conducted in areas where white men were the majority demographic group and study samples almost always reflected the demographic makeup where studies occurred. Additionally, those designing the studies seldom acknowledged race or gender differences, meaning they did not intentionally recruit diverse samples.

Furthermore, the journals publishing these studies did not have regulations requiring sample diversity, equity or inclusion as appropriate to the conditions under investigation.

“Marginalized groups have unique experiences from privileged groups, and when marginalised groups are poorly included in research, we remain in the dark about their experiences, insights, needs and strengths,” said Mallet Reid, co-author of the study and doctoral candidate in MSU’s Department of Psychology. “This means that clinicians and researchers may unknowingly remain ignorant to how to attend to the trauma and addiction challenges facing marginalised groups and may unwittingly perpetuate microaggressions against marginalised groups in clinical settings or fail to meet their needs.”

Source: Michigan State University