findings (Dobkin and Havton, 2004). In addition, as noted above, one of the issues raised in discussing clinical trials in this field is the use of alternative therapies that are highly experimental and that are not based on completed clinical trials or that are based on trials whose results are only putative (see Appendix F).
The International Spinal Research Trust (ISRT) recently asserted that continued advances in research laboratories will result in more experimental therapies being ready for clinical trials in the next few years. Furthermore, ISRT concluded that to meet this demand, new well-designed clinical trials that use novel tools to assess the effects of a treatment on the outcomes will need to be developed (Ellaway et al., 2004).
Useful lessons for future trials can be learned from the series of clinical trials that assessed the ability of methylprednisolone to improve the recovery of individuals after a spinal cord injury, including the original three National Acute Spinal Cord Injury Study (NASCIS) trials (Bracken et al., 1984, 1990, 1997) (see Appendix E). Although the authors of the NASCIS trials concluded that methylprednisolone should be a standard treatment for acute spinal cord injuries, many clinicians question its efficacy because of issues regarding the statistical analysis used to assess the improvements to the central nervous system and concern over adverse complications. The limitations of the studies in addressing some of the potential confounding variables may limit the extent to which the results of the studies can be generalized to all individuals with acute spinal cord injuries (Hanigan and Anderson, 1992; Bracken, 2000; Hurlbert, 2000; Dumont et al., 2001). For example, the NASCIS II trial did not include details about other interventions used (e.g., radiology, surgical manipulations, or the extent of rehabilitative therapies) that may have contributed to improvements or recovery (Hanigan and Anderson, 1992). Concerns have also been raised about the robustness of the statistical analysis and the heterogeneity of the injured population used in the studies, which made the baselines of the different populations difficult to compare (Bracken and Holford, 2002). Furthermore, although it was concluded that the NASCIS II and III trials were “well designed and well executed,” post hoc analysis of these trials “failed to demonstrate improvement in primary outcome measures” (motor scores, pinprick scores, and light-touch scores) (Hurlbert, 2000). Consequently, it has been stated that the data describing improved recovery with methylprednisolone treatment are weak and that the improvements observed may represent random events (Hurlbert, 2000). Some have also suggested that it should not be a recommended treatment (Hurlbert, 2000). However, concerns about the potential legal ramifications of not using methylprednisolone may cause some physicians to continue to treat their patients with the medication. To strengthen future trials, it is important to learn from the experiences of the NASCIS studies and other similar studies.