Innovative approaches to ensuring participant safety in early phase clinical research

Early phase first-in-human and patient clinical research is key to refining the safety profile of new drugs, expanding on the data gathered in preclinical studies. This stage typically requires the recruitment and participation of healthy volunteers, which emphasises the moral and ethical imperative for ensuring participant safety. Proper safety measures protect participants and also uphold the integrity of the research process, and regulators like the EMA and FDA have issued guidance for more stringent early-phase safety strategies that account for the increasing complexity of clinical trial protocols. These strategies have focused on starting dose, dose escalation and maximum dose,¹ but there are other site-level opportunities to proactively mitigate risks to patients.

��䰿�� early clinical research unit and bioanalytical laboratory in Groningen, Netherlands has served as a blueprint for early clinical trials around the world, due to their unique infrastructure and process design, including innovations around patient safety. Up to 40% of our studies are first-in-human, and we have implemented novel, collaborative programs to more effectively mitigate risks to patients.

Unique program with mutual benefits

Ensuring patient safety requires strategic planning at multiple levels, from protocol and dosing escalation to site-specific and personnel training. It is common for early phase clinical sites to have relationships with nearby clinics and hospitals to have direct access to intensive care in case of emergency. The 91�� research site in Groningen, Netherlands, led by our Medical Director and cardiologist Jan Leendert Brouwer, has gone further to drive innovative collaboration to centre patient safety.

Of course, 91�� staff are always trained in life-saving procedures so they can respond immediately if a patient should need them. However, with the growth of the Groningen research institute, 91�� sought a training partnership to ensure the efficiency and quality of the process. The neighbouring Martini Hospital was the ideal candidate. They were undergoing significant developments in their training and education at the time, expanding their training capacity, and agreed to become a certified training centre with status from the Dutch Resuscitation Council to provide this specialised training for ��䰿�� research centre teams. The Martini Academy became the only training institute of this kind in northern Netherlands and benefitted from a steady flow of trainees through 91��, resulting in mutually beneficial program growth.

The benefits of collaboration in medical emergencies

Training with Martini Academy ensures that 91�� and Martini Hospital employees are trained identically with the same materials, equipment and processes to enable highly coordinated execution across the teams. This is a vital benefit of shared training as Martini Hospital is also the responding clinic should patients require lifesaving medical assistance.

Beyond the classroom, the cross-organisation training extends to practice scenarios to further hone the response time and efficiency to optimise the safety of participants in the research centre. Annie, the practice dummy, is continually recast as the lead role in a wide range of potential scenarios. Sometimes she suffers a cardiac arrest, other times she falls down the stairs. The goal is to ensure the teams are prepared to respond to any potential situation. Supervisors from both teams evaluate the initiative, role assumption and efficiency and composure of the personnel, identifying potential areas to learn and improve. This unique form of collaboration is regularly practiced ensuring perfect coordination across the teams. Roles must be clearly defined, everyone must know what is expected of them, and protocols must be strictly followed.

The drills are co-developed with the Martini Hospital, though the staff are not made aware of the drill prior to the alarm that sounds, setting them into action. The alarm, the same one that the 91�� team utilises in emergency, opens the door to the air bridge that connects the Martini and 91�� buildings to ensure the dedicated resuscitation team from Martini can respond as quickly as possible. The Martini team arrives in just two minutes to support ��䰿�� resuscitation efforts and the continuity in execution ensures no time is lost in the transition, providing seamless, lifesaving care should a patient need it. Importantly, no patients have required this resuscitation team, in part thanks to other innovations implemented at the clinic that we describe below.

Novel tools for early recognition of safety signals

It has been found that in 80% of resuscitation cases, there were signs indicating a disturbance in vital parameters such as breathing or body temperature present up to 24 hours beforehand.² When these disturbances are not recognised, they cannot be adequately treated to prevent further risk and the chances of a poorer outcome are greater. Instead of channelling all site-level safety efforts into efficient responses, 91�� has taken a proactive approach to identifying risks to patient safety, resulting in the implementation of the Modified Early Warning Score (MEWS) in our research and screening centres.

The MEWS card is designed to fit into staff pockets to be readily available. The various vital functions and other important factors are assigned a score on the MEWS card, and the combined score determines whether there are indications of a 'vitally threatened participant' and triggers appropriate action. The MEWS score is also a key component within the new collaboration with the Emergency Intervention Team of Martini Hospital. It offers a shared shorthand for assessing patient risk so that the right response may be mobilised. For example, with a score of 4 or more, direct contact can be made with the Emergency Intervention Team for consultation and, if necessary, they will come on-site to assess the patient together with 91�� personnel to determine the best course of action to prevent serious risk. The MEWS card has been utilised on multiple occasions and the proactive approach has enabled early health-risk mitigation for two separate patients.

Innovating safety standards

Patients are the heart of what we do. Without patient and volunteer participation in early phase research, we would not be able to advance important medical research to bring meaningful therapies to patients in need. The implementation of proactive safety measures is the next step in innovating safety standards and evolving our approach to protecting patients at every step. The success of the unique collaboration with Martini Hospital and the MEWS scorecard has significant potential to guide other programs in their patient safety programs and other 91�� clinical research facilities are already harmonising SOPs.

Connect with us to learn more about early phase clinical development and how we can help prioritise your patients�� safety.

¹ . European Medicines Agency.

² van Galen LS, Dijkstra CC, Ludikhuize J, Kramer MH, Nanayakkara PW. . PLoS One. 2016;11(8):e0160811. Published 2016 Aug 5. doi:10.1371/journal.pone.0160811

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