Clinical trials (Paul Dark)
Clinical trials are the best way to ensure medicines and treatments are safe and work as intended. However, many important factors and safeguards must be considered and put in place before a clinical trial can begin, to ensure that patients are protected, and that results and findings are reliable. Researchers and the University also need to ensure they are safeguarded from legal or ethical risks. This applies to the testing of gene-therapy treatments for rare genetic disorders, the use of nanomaterials as a medical device, or any other health intervention.
This was particularly important with a recent major UK patient trial of a new biomarker testing protocol for sepsis, led by University of Manchester researchers, which showed it is possible to safely stop antibiotic treatment earlier than current care.
The study, commissioned and funded by the National Institute for Health and Care Research (NIHR) and led by Chief investigator Professor Paul Dark with partners in Northern Care Alliance NHS Foundation Trust and Warwick Medical School’s Clinical Trials Unit, found that antibiotics duration reduction of around 10% could provide significant cost savings to health systems, limit unwanted drug side-effects, reduce overtreatment and reduce the development of antimicrobial resistance in individuals, across communities and internationally.
The randomized controlled trial was based at 41 intensive care units across the UK, involving 2,760 adults from January 2018 to June 2024. It compared 918 patients on a procalcitonin (PCT) protocol with 924 patients on a C-reactive protein (CRP) and 918 patients on current standard care. Clinicians responsible for managing patients received daily standardized written advice on either standard care or on PCT or CRP biomarker-guided antibiotic discontinuation. The protocols in the study were uniquely designed to conceal laboratory test results from clinical staff to reduce potential bias and patients were randomly assigned to one of the three groups.
As study sponsor, the University of Manchester had legal responsibility to ensure that the trial required independent ethical review by an NHS ethics committee specialised to consider research for patients who may lack the mental capacity to make decisions about their care, involvement of patient representatives and care providers. Professor Dark said: “Being able to offer research participation to critically ill patients, supported by their families and carers, at a national scale is crucial to improve and advance patient care and its value. The highest quality health and care research is only possible within a rigorous governance framework and provides reassurances to everyone that the research is safe, deliverable and that the results are trustworthy.”
According to the charity Sepsis Research FEAT, around 50,000 people are estimated to die of sepsis in the UK each year, which develops when the body's immune system overreacts to an infection and starts attacking its own tissues and organs. Accounting for 100,000 hospital admissions a year in the UK, it is estimated that there are 49 million cases and 1 million deaths a year globally.
Recognising sepsis and starting antibiotics early are crucial but, until now, the recommended duration of such treatment has been uncertain. Doctors are currently recommended to use their judgement to decide when to discontinue antibiotics used to treat the condition.
The new decision support system Professor Dark’s team developed is based on a simple blood test, carried out daily and available in most NHS hospital laboratories. It tests for levels of a circulating protein called procalcitonin (PCT), which is produced as part of the body’s immune system responses to bacterial infections. A computer automated response, based on the PCT levels from the blood test, advises doctors whether to discontinue antibiotic treatment or not.
Professor Dark said: “This simple protocol, if implemented, could significantly change the way sepsis is treated and safely help to combat antimicrobial overuse and resistance - one of the world’s leading health challenges. This study would not have been possible without the generous contribution of patients with this life-threatening condition who, like all of us, are committed to finding better ways to deal with sepsis.”
Sponsorship in clinical trials
Sponsorship in clinical trials is inherently a dynamic function, involving continuous oversight and adaptation to maintain trial integrity, participant safety, and regulatory compliance. The University of Manchester manages this through the Clinical Trials Management Group (CTMG).
The CTMG comprises members of the University’s Research Governance, Ethics and Integrity Team, professional services personnel with extensive regulatory expertise and is led by senior clinical academics experienced in leading clinical trials. This group provides oversight for all the University's clinical trials and other high-risk interventions.
While the Chief Investigator focuses on the operational aspects of the trial, the CTMG provides oversight, support, and ensures compliance with broader regulatory and institutional requirements. This division of responsibilities helps ensure that clinical trials are conducted safely, ethically, and effectively.