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Plasticity White Paper (PDF - 121KB)

Created on March 21, 2011

6 Submitted Comments on Plasticity

As the authors have writen, the term "plasticity" is most often used in reference to the CNS. I am interested in types of non-CNS tissue plasticity - i.e. the use of in vivo growth induction. For example, in pediatric patients with esophageal atresia physical traction is applied to induce growth (not stretching) of esophageal tissue. The result is a normal esophagus. What is NICHD's interest/resources to support such novel approaches to traditionally recalcitrant surgical problems?

Submitted by Maya Greer on May 10, 2011 at 1:33 PM

The following comments are from doctoral students (Christofaris, Golla, Hamilton, Rivera, Sonstrom, & Speights) in Communication Disorders at the University of Cincinnati. The student group is primarily interested in neural plasticity as it applies to behavioral interventions used to improve speech, cognition, and language. Our discussion included the following: 1) Is the term biomarker appropriate for speech and language behaviors, and if so, what are some examples? We assume that biomarkers would include innate behaviors that could be observed in naturalistic settings. Performance on tests of speech and language with multiple responses would not be biomarkers. 2) We questioned the role of motivation and its neurochemistry in neural plasticity. Motivation has always played an important role in behavioral change but what is the neurochemistry or neural mechanism associated with motivation? Might the degree of motivation override the contribution of the specific behavioral therapy introduced by a clinician? 3) We noted that large sets of data for speech and language research in disordered populations are not widely available to researchers. We agree that establishing national research networks, more accessible data bases, and making standardized treatment protocols available would be helpful. Studies that include small numbers of participants are most common in speech and language research. Because of the large variability among participants in various populations affected by speech, language, or cognitive impairments, it is very difficult to minimize the effect of inter-subject variability. For example, speech, language, and cognitive abilities of individuals recovering from traumatic brain injury are variable to the extent that the effect of an intervention varies considerably from participant to participant. 4. We also acknowledged the importance of training clinical researchers, who are willing to collaborate across disciplines and provide data from their day to day clinical practice for large scale studies.

Submitted by Jean Neils-Strunjas on May 11, 2011 at 3:09 PM

Regarding the section on Process Opportunities: The comments about adoption and about regulation would benefit from an exposition of anticipated obstacles specific to plasticity-related interventions. It would provide greater guidance to NICHD and would be likely to have greater influence on policy discussions.

This is an issue particularly for the second process opportunity, on regulatory barriers. The topic raised here has been and continues to be discussed extensively, and the many issues about specific regulatory and adoption barriers are not really touched on in this brief statement. Furthermore, the section as it stands reads more as an advocacy statement than a dispassionate explanation of barriers and how they might be addressed. The points made here have been made by many individuals and groups. There are ongoing federal and private efforts to harmonize regulation and to ensure that CMS coverage processes are improved. A more nuanced and detailed statement would be more likely to influence the policy discussion.

Submitted by Alan Garber on May 29, 2011 at 7:41 PM

The bottom line for getting information from rigorous basic and translational studies into clinical practice is well-designed clinical trials, We should make sure current practicies and future goals of clinical trials are accurately articulated. One point is that current and recent clinical trials have not necessarily addressed mechanism. Inmy ex[perience as an NINDS study section member for clinical trials (including trials of rehabilitation), in fact mechanism is often UNDEREMPHASIZED, and trials are often funded as "black box" experiments. I would alter the first sentence of Scientific Opportunity 4 to say: "Efficacy trials focus on impairment-based outcomes and comparison with placebo, providing scientific rigor for efficacy within the trial, but often lack mechanistic framework. Although efficacy trials have attempted to validate numerous plasticity interventions such as contraindicated-induced movement therapy, robotic therapy, mental practice, bilateral movement therapy, and electrical stimulation, a lack of mechanistic understanding can lead to difficulty generalizing across different patient populations. Prior to acceptance by the clinical community..."

Also, regarding numbers needed for clinical trials, Phase III trials may require large sample sizes, but phase II trials that focus on mechanism and dose optimization may be done with smaller sample sizes. A 2-phase grant process has been used with some success in NINDS: in a single proposal, establish optimum dose, then proceed to a randomized, controlled clinical trial.

Submitted by Randolph Marshall on May 30, 2011 at 4:46 PM

The American Occupational Therapy Association (AOTA) represents over 140,000 occupational therapists, occupational therapy assistants and students of occupational therapy. As the national association representing occupational therapy, a profession dedicated to maximizing independence and function for people across the lifespan, AOTA lauds the participants of the plasticity workshop for considering basic science, clinical science, and translation.

AOTA commends the authors of the white paper for emphasizing the mechanisms of different forms of plasticity so that we can better understand complex disorders and develop effective treatments. While it is important to examine how therapies, such as occupational therapy, can manipulate plasticity through functional and therapeutic activities, we must be cognizant of other variables that can also influence plasticity. For example, age, sensitive periods, genetics, and environments may influence the degree of plasticity or related outcomes.

We agree that improved clinical trial designs could enhance plasticity-based therapies and optimization research should be supported and recognized as critically important pieces of the "translation" puzzle. In rehabilitation and possibly other fields, considering disease severity may be important when examining the efficacy and effectiveness of plasticity-based clinical interventions.

AOTA supports the need to evaluate the effects of combination therapies on plasticity (scientific opportunity 5). In addition to drugs, assistive technologies, rehabilitation therapies, and environmental supports may greatly influence plasticity.

Finally, process opportunities include examining rewards and incentives for the research that's needed. Some early career scientists are being advised against conducting some types of research because it would take too long for the promotion and tenure cycle. For some, tenure focuses on the individual's accomplishments and expertise, not necessarily being an integral member of a research team conducting important research. Although NICHD cannot influence academia, are there ways to encourage universities to update their tenure criteria and processes? Also, NICHD may want to consider working with professional organizations so that specialty certifications could require knowledge or clinical expertise with new therapies, as a means of facilitating implementation of new therapies by clinicians.

Thank you for providing this opportunity to c

Submitted by Susan Lin on June 10, 2011 at 8:26 AM

The Society for Women's Health Research (SWHR) appreciates the opportunity to provide comments to NICHD's Vision process. SWHR strongly encourages the Workgroup on Plasticity to examine the role that biological sex plays in the body's natural ability to heal itself, particularly in the area of the brain.

Research has demonstrated that the male and female brains are fundamentally different (Differences in the Brain From Genes to Behavior, 2008) and more research is needed into the role that sex plays in the process of rehabilitation. Further, sex should be identified as a variable in identifying response to therapeutic intervention, prognosis, and risk. As such, studies working on a diagnostic or treatment aiming for regulatory approval for use in women and men should accrue enough women to allow for sufficiently powered analysis by sex.

Chronic pain, a focused area of interest for the Workgroup, is a good example of a problem in which sex clearly plays a fundamental role. Chronic pain conditions (fibromyalgia, irritable bowel syndrome, rheumatoid arthritis, migraines, etc) are more prevalent in women than men, and there are sex differences in drug efficacy and side effects. Although genetic and hormonal differences may be paramount, social and psychological factors are also important and need to be investigated.

The search for new biomarkers, another concern of the committee, is an area where biological sex must not be ignored. As the study of biomarkers mark another step towards personalized medicine, the committee must acknowledge the role that sex plays as a variable in health and disease. As the Workgroup endeavors to discover new tools and treatment strategies over the next 10 years, SWHR urges the NICHD to consider interdisciplinary and multidisciplinary approaches to improve the speed of translation of basic science to clinical practice.

As the thought leaders in research on sex differences, it is SWHR's hope that NICHD will be cognizant of sex as a variable with regard to new approaches in plasticity and when identifying new biomarkers.

Submitted by SWHR on June 10, 2011 at 9:36 AM

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Last Reviewed: 06/04/2012