Prior to the finalization of a complex protocol and/or during the start up of a study that has unique training needs, we will institute the use of the Duke Human Simulation and Patient Safety Center (HSPSC) for two distinct purposes; protocol “usability”/design, and immersive training of research personnel.
Researchers in the HSPSC have demonstrated phenomenon consistent with learning curves in the data record of several clinical trials1 and have described the benefits of applying simulation techniques in the development and start-up of clinical trials.2,3 There is emerging evidence that learning curves may negatively influence the outcome of large multicenter clinical trials4 and the frequency of adverse events.5 The HSPSC is pioneering the use of human factors methods and simulation to mitigate learning curves in clinical trials. The application of our methods provide long term benefits to patients, trainees, and sponsors, including protection of the sponsors investment in their drug or device, the reduction of research cost and most importantly, reducing the potential risks to real patients. Simulation (mannequin-based or actor-based) is typically used in two ways: 1) protocol walk-throughs and 2) research personnel training.
Walkthroughs are used to assess protocol design. Protocol developers observe their study performed by research personnel in a high-fidelity simulated clinical setting prior to subject enrollment. Viewing (and reviewing) walkthroughs of clinical protocols helps uncover issues with design, timing, complexity, and practicality. Potential protocol errors and inefficiencies are highlighted and can be corrected before the protocol is implemented, thereby minimizing subject exposure and the number of protocol amendments—ultimately impacting both safety and cost.
In addition, skill acquisition of the research personnel is a key factor in the safe and effective deployment of a clinical research protocol. Proper performance of a clinical trial depends on complex behaviors. Complex human behaviors demonstrate ‘learning curves’, where performance improves with repetition. Just like a sports team, proficiency is gained through practical experience. Interactive training in a simulated environment provides the opportunity for Investigators, coordinators, and monitors to ‘practice’ without placing subjects or data at risk. Following simulation training, research personnel are closer to optimal performance at the time subject enrollment begins.
Ultimately, we believe our methods improve the chances of a successful trial (through better design and enhanced research personnel performance) while minimizing cost, improving efficiency, and enhancing safety.
Two examples of protocols using the simulation training are:
- A Phase II multicenter, randomized, double-blind, parallel group, dose-ranging, effect-controlled study to determine the pharmacokinetics and pharmacodynamics of Sodium Nitroprusside in pediatric patients, sponsored by the NIH.
- A Phase III, multicenter, randomized study of the safety and efficacy of Heparinase I versus Protamine in patients undergoing CABG with and without cardiopulmonary bypass/ sponsor by sponsored by an industry pharmaceutical company.
1. Taekman JM, Stafford-Smith M, Velazquez EJ, Wright MC, Phillips-Bute BG, Pfeffer MA, et al. Departures from the protocol during conduct of a clinical trial: A pattern from the data record consistent with a learning curve. Qual Saf Health Care 2010, Aug 10.
2. Wright MC, Taekman JM, Barber L, Hobbs G, Newman MF, Stafford-Smith M. The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures. Contemp Clin Trials. 2005;26:646-659.
3. Taekman JM, Hobbs G, Barber L, et al. Preliminary Report on the Use of High-Fidelity Simulation in the Training of Study Coordinators Conducting a Clinical Research Protocol. Anesth Analg. 2004;99:521-527.
4. Macias WL, Vallet B, Bernard GR, et al. Sources of variability on the estimate of treatment effect in the PROWESS trial: implications for the design and conduct of future studies in severe sepsis. Crit Care Med. 2004;32:2385-2391.
5. Laterre P-F, Macias WL, Janes J, et al. Influence of enrollment sequence effect on observed outcomes in the ADDRESS and PROWESS studies of drotrecogin alfa (activated) in patients with severe sepsis. Critical care (London, England). 2008;12:R117.