The Collaboration seeks support to develop an infrastructure for rigorous multi-center clinical investigations (Clinical Trial Network, CTN) to identify and fast track promising potential treatments through clinical trials. In our experience, these infrastructures are costly but necessary to conduct multi-centered trials with high fidelity and reproducibility. This clinical research Collaboration, working with the OMF-supported Stanford ME/CFS Collaborative Research Center, represents a unique opportunity to establish standards and infrastructure for rigorous clinical investigations and trials in ME/CFS. The Collaboration will be designed to evaluate the potential for new ME/CFS therapeutics and to conduct well designed, Clinical Research Organization (CRO)-supervised pilot and pivotal clinical trials for repurposing already FDA-approved drugs for new indications in ME/CFS and for the drug development of novel promising compounds.
There is interest within the faculty of the Harvard ME/CFS Collaboration to conduct pilot clinical trials using Food & Drug Administration (FDA) approved drugs to evaluate the potential for these drugs to receive approval for an FDA indication for ME/CFS patients. There are currently no drugs in the formularies of any hospitals and clinics with approved FDA on-label usage in ME/CFS patients. Most all drugs commonly used in patients are off-label usage and their usage comes from privilege of practitioner’s prerogative for usage of medications off-label. The clinical rationale is most often on the basis of a weakly powered single site study with or without a publication or more often, simply the practitioner’s prior experience in their local practice. Neither rationale should form the sole basis going forward regarding a better understanding of ME/CFS as a disease nor the development of future therapeutic interventions. These initiatives are expensive and funds to support these capabilities of the Collaboration are sought.
Drug development should arise from fundamental discoveries in the underlying pathophysiology leading to rational drug targets. In the absence of such information and on the basis of the current limited knowledge in the ME/CFS field, an alternative approach might be to pursue currently-approved drugs in “Pilot Studies” with the hope that the targets of these drugs might also be therapeutic in ME/CFS patients. For those drugs that show great promise, trials could then be designed to better understand any subpopulations of ME/CFS patients who might benefit most from the use of the pilot study drug. Once promising subpopulations were known, the FDA-pivotal trials can then be pursued to create specific indications for these drugs in those subpopulations of ME/CFS patients.
These pilot studies would be subject to Institutional Review Boards (IRBs) of the participating Hospitals and might require an Investigational New Drug (IND) application. Pilot studies that would not require an IND are strictly defined in this regulation under the purview of the FDA and described in the “Guidance for Clinical Investigators, Sponsors, and IRBs Investigational New Drug Applications (INDs) — Determining Whether Human Research Studies Can Be Conducted Without an IND”. The ME/CFS Collaboration faculty is very familiar with these obligations and is well-supported to fulfill these regulations.
Clinical Research at MGH:
The Massachusetts General Hospital (MGH) has a Division of Clinical Research (DCR) that houses multiple clinical research entities. The Translational Clinical Research Center (TCRC), which is a component of the DCR, was established in 1925 and it has contributed much to what is known about endocrinology in medicine. The TCRC is one of the very few of the 61 Clinical Research Centers in the United States to incorporate imaging into its core operations.
Another resource, Translational Research Center (TRC), is within the DCR and the Center for Computational and Integrative Biology (CCIB) of which, Dr. Tompkins is a faculty member. The TRC is designed as an extensive clinical research platform available to support pilot studies and ultimately pivotal trials as required by a study sponsor. A component of the TRC is an institutional-based Clinical Research Organization (CRO) capable of fulfilling all FDA requirements for approval. Of the TRC’s studies, most are federal or foundation-funded trials but approximately 20% of its studies are funded by industry. The TRC features an in-house laboratory, metabolism and nutrition services, and staff research nurses and nurse practitioners to facilitate the studies. This resource would be excellent to establish a core support operation in this early development period for our virtual Center at the Harvard-affiliated Hospitals. Taking advantage of the TRC makes this option cost-effective while the Center of Excellence is under development. Outsourcing the FTE’s involved in the process of these clinical trials, which is available within the TRC, makes fiscal sense until a sufficient number of clinical studies justify a dedicated staff and the resources present within the Center of Excellence. So the budget for this activity will be calculated based upon a per drug trial and per patient basis as an outsourced service.
These challenges are well-known to the faculty and they are willing to face these challenges as sufficient support becomes available. The development of the Clinical Trial Network (CTN) will be updated on the site as the needed resources and support become available.