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Introduction to the Pharmaceutical Interventions for Hearing Loss Clinical Research Guidance Papers

Hammill, Tanisha L.; Packer, Mark

doi: 10.1097/MAO.0000000000001155

DOD Hearing Center of Excellence, JBSA Lackland, TX,

The authors disclose no conflicts of interest.

Both Military and Civilian noise threats continue to claim casualties. Degradation of quality of life and limitations in communication, opportunities, and performance can be expected to continue to escalate, marginalizing significant portions of the nation. Every year, hearing injuries top the lists of Veterans Affairs (VA) disability tables. Over 2.3 million Veterans claimed an auditory injury in fiscal year 2014 alone (2014 Annual Veteran Benefits Report). While noise control engineering, administrative noise exposure controls, and hearing protection education and devices are all important tools in the military arsenal against noise injury, a pharmaceutical tool to augment prevention or mitigate injury is needed.

The increasing volume of research activities, from basic research through clinical trials, currently underway to understand the mechanisms behind hearing loss as well as potential pharmaceutical interventions that may reduce this health issue is both incredibly exciting and often difficult to keep up with. The Pharmaceutical Interventions for Hearing Loss (PIHL) working group was chartered in 2012 by the Department of Defense (DOD) Hearing Center of Excellence (HCE) to review and maintain state of the science knowledge of these translational therapies for the prevention and rescue of noise- and ototoxic-induced hearing loss. The group is comprised of nearly 175 members, voluntarily participating from DOD, VA, Centers for Disease Control (CDC) National Institute for Occupational Safety and Helath (NIOSH), Food and Drug Administration (FDA), Academia, Industry (both biotechnology and venture capital firms), as well as international partners and stakeholders.

To date, PIHL scientists have no defined standards to guide study design. Instead, they must rely on cursory reviews of existing articles, mentored practices, or their own best judgment. The lack of homogeneous study designs result in incomparable, and thus disputable, study outcomes which, in turn, delays in our ability to understand and progress the state of the science. The PIHL group's charter calls upon the members to determine and maintain the current and comprehensive state of the science. This foundational knowledge was to be used to spotlight minimal functional performance requirements of potential agents, and importantly, to identify the evidence-based laboratory, animal, exposure, and clinical assessment methodologies that can be considered “best research practices.” In turn, adopted use of such recommendations should promote homogenous research outcomes and, thus, comparability across trials investigating new drug development.

The PIHL working group quickly concluded that any guidelines, in the strict sense of the word, would require a more thorough understanding of the field than has been conducted to date. Rigorous reviews have not been conducted which can definitively identify best practices across the spectrum of study designs in PIHL research. Therefore, in anticipation of a systematic review, the HCE herein offers interim guidance, which is the culmination of 3 years of working group discussion, literature review, and open dialogue. Additionally, two states of the science symposia were hosted by the HCE for experts across the translational spectrum of research, including those working with front-running candidate drugs performing animal studies and clinical investigations. All discussion focused on analyzing the issues most relevant to participation in Investigational New Drug (IND) development and translation of the science for the prevention and/or rescue of hearing loss.

Simultaneously, the HCE is tackling the recommended full systematic, descriptive review of peer-reviewed PIHL studies to better understand the various elements of study methodologies being employed across the field. Using PIHL literature attained through systematic review methods consistent with current standards, the review effort will identify, characterize, evaluate, and correlate the methodological variables across PIHL studies, from animal to human. This assessment will focus on the research designs in PIHL investigations, with the objective of producing conclusive, evidence-based sets of “best research design practices.” In so doing, the hope is to contribute to the current understanding of the state of the science and identify any trends across studies in this field, which can refine the way toward standardization in PIHL study design. The guidances offered in the following pages will be considered living documents, subject to updates as new evidence emerges suggesting improvements in study design practices which can further advance the field, particularly as a result of the PIHL Methodology Systematic Review project.

In all scientific disciplines, investigators are free to design their research according to their preferred style and philosophy, beholden to justify choices through literary reference when available. But, when literature is as methodologically heterogeneous as PIHL literature, investigators are left to a great deal of choice. The following articles aim to provide direction by the authority of consensus not to limit investigator choices but to instill confidence and standardized justification for the choices they make. And while these views are not yet based on rigorous systematic review, the process of subject matter review, debate, and experience, coupled with PIHL advisory consensus to bridge literature gaps in this developing field of research produced confident recommendations for appropriate standards, technologies or suggestions to guide future PIHL studies.

This successful consensus in the face of an interdisciplinary, interinstitutional, and competitive composition of the PIHL working group is a testament to the passion for and commitment of all involved to the advancement of the science. This broad field of experts has defined a functional way ahead that will boost the progress of everyone interested in participating in the advancement of Pharmaceutical Interventions for Hearing loss. The HCE will continue to facilitate collaborations with military study populations and establishing requirements for technology transition within the DoD. Finally, the HCE will continue to support continual evidence-based recommendation and administrative facilitation to construct best research practices for DoD stakeholder implementation.

We would like to thank Otology and Neurotology, Lippincott Williams and Wilkins, and the late editor-in-chief, John K. Niparko, M.D. for the opportunity to present these important guidance documents in this issue. We would also like to thank Samantha Martin and Mariana Hagan, editorial coordinators, for their coordination and direction. Finally, we would like to thank the authors, coauthors, and all peer reviewers for their dedication and volunteered efforts toward creating this first-of-its-kind collection of “best research practices” in the field of pharmaceutical interventions for hearing loss.

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