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6 Developing New Therapeutic Interventions: From the Laboratory to the Clinic
Pages 152-182

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From page 152...
... Finally, the unique challenges of designing and implementing clinical trials of treatments and therapies for both acute and chronic spinal cord injuries and the tools needed to improve the efficiencies of clinical trials are discussed. The development of new medications or devices that target a specific complication, such as preventing or reducing neuropathic pain, can take an average of 15 years (Quest for new cures, 2003; PhRMA, 2004a)
From page 153...
... Phase II and phase III clinical trials evaluate the efficacy of the new intervention and examine adverse effects in studies with larger populations. In the end, a novel drug that has entered a phase I clinical trial has only an approximately 30 to 40 percent chance of successfully completing a phase III clinical trial and being approved by the Food and Drug Administration (FDA)
From page 154...
... The challenge is to develop therapies in a timely fashion without undermining future scientific endeavors and, most importantly, without endangering patient safety. CRITERIA FOR VALIDATING A NOVEL THERAPY The spinal cord injury research community is making substantial progress in developing novel therapies that may soon be ready for clinical trials.
From page 155...
... These efforts would enable the scientific community to scrutinize the data and would provide information to the spinal cord injury patient population on the results of preclinical and clinical testing of all novel therapies.
From page 156...
... : · the study should address an important research question that cannot be answered by use of an alternative study design; · the scientific community has reached a consensus about the safety of the proposed experiment on the basis of the findings from preclinical studies; · evidence that the intervention might ultimately be beneficial is sufficient; · the clinical trial design is based on sound science and has minimal risks and maximal benefits, the outcomes are measurable and meaningful, and the selection of subjects is fair; and · valid informed consent is obtained from each participant. Concerns have been raised about the experimental therapies that are being requested and tried by individuals with spinal cord injuries, even though the interventions have not been assessed for safety and efficacy in
From page 157...
... Until the results of the clinical trials are obtained, however, the spinal cord injury community should be cautioned against receiving such therapies. As Rosenfeld and Gillett have noted, "[s]
From page 158...
... . A 2004 review concluded that many of the most-cited clinical trials of interventions for spinal cord injuries had methodological limitations that hinder interpretation of their results and the ability to generalize their 60 40 articles of 20 Number 0 Pain care health sores Cough function density Imaging spasticity FES/FMS measures response responsetherapySurgery Acute Respiration Bone Immunology Bladder/bowel Mental Cardiovascular Syringomyelia Sexual Muscle, Neural Alternative Exercise/locomotion Outcome Physiological Ulcers/pressure FIGURE 6-1 Publications on clinical trials for interventions for spinal cord injuries (1998 to 2003)
From page 159...
... . 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)
From page 160...
... For patients who do not have the capacity to give informed consent, legal proxy can be obtained from a family member or a guardian. Therefore, obtaining informed consent for most clinical trials that examine interventions in the chronic stage of spinal cord injury has not been a major hurdle.
From page 161...
... . 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.
From page 162...
... These challenges may limit the number of individuals available for a clinical trial, although there are opportunities to use existing regional patient care centers to facilitate access to clinical trials. To increase the number of individuals with spinal cord injuries as potential clinical trial participants, health care professionals must be aware of ongoing clinical trials so that they can educate their patients about the available options and the benefits of participating in clinical trials.
From page 163...
... report (2001) recommended that the following steps be followed: · clearly define the research question; · tailor the study design by giving careful consideration to alternative methods and involve statisticians early in the design process; · clarify sample characteristics and methods for reporting the results of clinical trials with small sample sizes; · perform corroborative analyses to evaluate the consistency and robustness of the results; and · exercise caution in the interpretation of the results before attempting to extrapolate or generalize the findings.
From page 164...
... . Many of these methodologies have not been field tested in situations typical of spinal cord injury clinical trials; therefore, it may be appropriate to develop a research initiative to gather experienced clinical trialists to provide recommendations on how small "n" clinical trials could be effectively applied to spinal cord injury clinical trials.
From page 165...
... FDA allowed the application for premarketing approval to be submitted with less than 30 subjects. In a second clinical trial of a bladder neuroprosthesis, the individual's perfor mance was determined in the same three states described above: preoperatively and postoperatively with the prosthesis off and on (Creasey et al., 2001)
From page 166...
... . private-industry sponsors of clinical trials prefer to use central IRBs for multicenter clinical trials, because a single process of review and approval can be used and the average time required to obtain approval is reduced (Loh and Meyer, 2004)
From page 167...
... Coordination of Care and Cure Efforts It is important that ongoing efforts related to patient care and rehabilitation after a spinal cord injury be coordinated with efforts in developing therapeutic interventions for spinal cord injuries. A number of sites and systems can be used to conduct clinical trials of interventions for spinal cord injuries.
From page 168...
... Spinal Cord Injury Service is another extensive resource with a large patient population and health care professionals with clinical expertise in rehabilitation medicine. VA, which has a number of clinics throughout the United States, has an already established infrastructure that could be used to help clinical trial administrators educate and recruit members of the community into clinical trials.
From page 169...
... · Is an 18-item, seven-level ordinal scale · Is designed to assess areas of dysfunction in activities that commonly occur · The scale has few cognitive, behavioral, and communication-related functional items · Is not specific for spinal cord injuries but is designed to assess neurological, musculoskeletal, and other disorders Functional Assessment Measure (FAM) · Was developed to augment the FIM · Specifically addresses functional areas that are relatively less emphasized in FIM, including cognitive, behavioral, communication, and community functioning measures · The scale has few cognitive, behavioral, and communication-related functional items · Is not specific for spinal cord injuries but is designed to assess neurological, musculoskeletal, and other disorders Spinal Cord Independence Measure (SCIM)
From page 170...
... has recently published a set of guidelines for clinical trials (ICORD, 2004) and is in the process of developing clinical outcome measures for each type of intervention.
From page 171...
... The scale is used to quantify an individual's total disability and can be used to monitor the progression of the disease. Currently, both the ISRT and the Christopher Reeve Paralysis Foundation are in the process of developing new assessment techniques for use in large-scale clinical trials of interventions for spinal cord injuries.
From page 172...
... Increasing Industry Involvement The level of investment in research and development on interventions for spinal cord injuries by the pharmaceutical and medical device industries is difficult to determine. A number of clinical trials of medications have focused on improving bowel, bladder, and sexual function (see Appendix G)
From page 173...
... . It is unclear whether the incentives provided by the Orphan Drug Act are sufficient to attract pharmaceutical industry investment in therapeutic interventions for spinal cord injuries.
From page 174...
... Discussions are needed among the range of stakeholders in the development of new therapeutics for spinal cord injuries, including federal and state health agencies; professional societies in neuroscience and clinical medicine; academic institutions; basic and clinical researchers; and biotechnology, medical device, and pharmaceutical companies. Coordination and Expansion of Spinal Cord Injury Registries and Databases Registries are online systems for storing and relating information about individuals (Box 6-5)
From page 175...
... The Consortium of Multiple Sclerosis Centers established The North Ameri can Research Consortium on Multiple Sclerosis (NARCOMS) : Multiple Scle rosis Patient Registry in 1993 to speed the development of new therapies and health care services by facilitating research on multiple sclerosis and reducing the time and cost of research studies.
From page 176...
... This type of registry could be used to understand the effectiveness of specific treatments, including practices or programs for improving functional outcomes and quality of life. Spinal cord injury registries could also provide a mechanism for identifying and contacting potential participants regarding clinical trials or notifying individuals about new therapeutic interventions.
From page 177...
... Efforts should be made to develop standardized protocols for patient registry systems so that registries can be coordinated and used to assist in identifying candidates for participation in clinical trials and provide information on upcoming clinical trials to individuals with spinal cord injuries (see Chapter 7)
From page 178...
... RECOMMENDATIONS Recommendation 6.1: Facilitate Clinical Trials Mechanisms should be implemented that will facilitate the implementa tion of clinical trials while observing the established standards for the protection of human subjects in clinical research, including: · Utilize and coordinate existing facilities and resources in acute care, chronic care, and rehabilitation to support multicenter clinical trials. · The use of central institutional review board mechanisms in con junction with local institutional review boards should be explored to facilitate coordinated multicenter studies.
From page 179...
... 2004, February 24. Challenges of Conducting Clinical Trials on Spinal Cord Injury in Industry.
From page 180...
... 2003. Influence of patients' age on functional recovery after transplantation of olfactory ensheathing cells into injured spinal cord injury.
From page 181...
... 1999. A Report on the Sponsors of Cancer Treatment Clinical Trials and Their Approval and Monitoring Mechanisms.
From page 182...
... Clinical Trials: A Practical Approach. New York: Wiley, Inc.


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