This change in language has made a significant difference in the ability of clinical trials of emergency medical treatments to proceed.
An illustration of the need for careful consideration of the design of clinical trials for acute-care interventions is found in the National Acute Brain Injury Study: Hypothermia trial. That study, which was initiated in 1994, before the new waiver consent rules were implemented, examined whether cooling the brain to 33°C within 8 hours of the injury could prevent further secondary damage. No positive effect was found; however, the details of the study design demonstrated the need for timely waiver consent (Clifton et al., 2002). During the first 9 months of the study, on average, it took close to 12 hours to obtain informed consent, initiate the treatment, and achieve the target temperature. However, after the new regulations were passed and the study design was changed to include waiver of consent if a responsible family member could not be located within 1.5 hours after admission of the injured patient to the hospital, the average time dropped to 7.9 hours (Clifton et al., 2002). The authors argue that it would be “impractical and unjust to perform studies of acute brain injury without use of waiver consent when the treatment window is less than six hours” (Clifton et al., 2002). Many similar issues apply to clinical trials for the emergency treatment of spinal cord injuries, and informed-consent waiver guidelines should be developed and standardized for use in clinical trials of interventions for acute care for spinal cord injuries.
Clinical trials require an adequate number of participants to ensure that the study groups are representative of the larger patient population and to overcome the variations in results unrelated to the intervention (Pocock, 1983). Furthermore, it is important that the control groups be as homogeneous as possible so that valid comparisons can be made. The combination of these two requirements results in narrow eligibility criteria and, thus, can result in longer patient accrual times (NRC, 1993).
For example, when Acorda was recruiting individuals with spinal cord injuries for a phase III trial of 4-aminopyridine (fampridine), it was estimated that about 1,200 patients would have to be screened to locate 400 patients who met the broad eligibility requirements (inclusion criteria) for the study (Blight, 2004). This process can be much more difficult for trials that have stricter inclusion criteria. The number of potential patients is made even smaller because few individuals enroll in clinical trials. For example, according to the National Cancer Institute, only 2 to 3 percent of cancer patients are ever enrolled in clinical trials (IOM, 1999). It is not totally clear why these numbers are so low, even though the general population is increasingly aware of clinical trials. However, the eligibility re-