COSTA MESA, Calif., Oct. 25 /PRNewswire-FirstCall/ -- CNS Response, Inc. announced today that it has conducted a quality assurance analysis of its current multi-center trial of rEEGSM -guided pharmacotherapy for individuals with treatment-resistant depression. Based on the evaluation, CNS Response is amending the design of the study in order to address issues related to functionality and operability.
Changes to the trial design will include (i) un-blinding the treatment physicians, (ii) incorporating the STAR*D treatment algorithm instead of the Texas Medication Algorithm Project (TMAP) as a comparative measure against which rEEGSM will be evaluated, and, (iii) modifying the inclusion criteria of the trial subjects. The modifications resulted from a joint review by CNS Response’s executive staff, the Company’s Scientific Advisory Board, its regional medical directors, specific trial site medical leadership, and the clinical study management team.
Implementation of these changes will result in a delay in interim and completed trial results from this study. The delay is dependent on the individual site’s approval processing of the protocol amendment. The amendment, however, also creates a second depressive patient group study that will be started alongside the first. It will leverage, recruiting, trial management and site training efforts associated with the first study. This will result in CNS Response reporting results of this second study sooner than previously anticipated by corporate plans.
The current nationwide study was designed to examine the efficacy of rEEGSM-guided pharmacotherapy in comparison to generally accepted therapies for individuals with treatment-resistant depression. This follows a pilot study in which 87% of patients guided by rEEGSM were successfully treated as compared to 17% of patients treated without the benefits of rEEGSM analytical reports. In total, eleven sites were to participate with a target enrollment of 120 subjects.
Len Brandt, CEO of CNS Response, commented, “The original design of our Treatment-Resistant Depression Study developed from conversations with scientific and academic advisors, but there really was not a model for such a study. Following our quality assurance assessment, we reached the conclusion that the methodology was not as practical to implement as hoped. As a result, we are modifying the trial design in order to enhance its overall functionality and ensure the integrity of the results.
“This process will delay our ability to complete the multi-site study as originally projected. We expect, however, that the new trial design will ultimately improve the speed by which patients can be tested and treated. The new design will also allow us to introduce an additional arm involving patients with a different depression indication. We expect that the re-design will eliminate the need for a previously-contemplated second study and will now allow us to generate a robust set of results earlier than previously estimated. Together these two studies, along with the prior-reported successful pilot study, should provide CNS Response with a strong set of results showing the efficacy of rEEGSM in guiding patients who failed initial depressive treatment.
“The three key changes that we are making to the trial design involve un- blinding the treatment physicians, using the STAR*D treatment algorithm instead of TMAP, and adjusting certain trial subject qualifications.
“The need to blind the treatment physicians was a product of the original trial design which called for the patients, treating physicians, raters and rEEGSM technicians to be blind to which patients were in each arm of the study. This arrangement proved difficult to implement because many of the site’s treating physicians felt the ethical need to understand the basis of treatment with selected medications in order to better dose and monitor the patients. Further, the fact that the treating physician was blind prevented the physician from considering the rEEGSM report alongside the standard clinical information of the patient when developing the treatment strategy. Of course, in clinical practice this integration of rEEG and clinical data is exactly what is done. So, this change will better mimic general clinical practice.
“As a result, we have concluded that a treatment design that attempts to blind the treating physician is operationally impractical. To adjust the design so that the measurement of outcomes is insulated from the treating physician, we will have an independent rater at all trial sites that will remain blind during the data collection and evaluation process. We will also use standard accepted patient self-rating scales as primary measures of outcome.
“Our interest in switching from TMAP, treatment algorithm to STAR*D is related to functionality and efficiency. The original study design involved comparing treatment results of patients guided using rEEGSM versus those directed by TMAP. However, one of TMAP’s advantages in the field - providing multiple options to the treating physician - caused complications during the study.
“It was clear to our advisors that if we were to continue with the TMAP, a separate TMAP expert would be needed to guide the treating physicians. STAR*D, the nation’s largest real-world study of depression, has recently completed an analysis suggesting treatment options with the highest probability of success for patients at various stages of treatment. By choosing the options shown to have the highest success, we can have a comparable arm with less variability and less need for expert interpretation. As such, we have concluded that the treatment design can be simplified by using the STAR*D results in the control arm of the study.
“Lastly, we encountered two obstacles with the trial subject qualifications that required attention. The first involved trial subjects whose treatment strategies would be similar under either TMAP or rEEGSM. In these situations, there is actually nothing to test, since under random assignment to either study arm, the patient would be treated the same. In addition to this being costly, depending on how such patients are assigned to either arm of the study, there is a chance that these patients can obfuscate study results. To combat this potential problem, we have concluded that the treatment design should exclude patients who would be treated the same way under both treatment arms.
“The second trial qualification involved defining treatment-resistant patients as those who failed a minimum of three previous treatment efforts. We found many challenges with this strict classification. In some cases, failed treatment included medication that had been successful for many years prior to failure but eventually lost effectiveness. While other patients who had seemingly failed many medications, in actuality, only failed a single class of medication, Selective Serotonin Reuptake Inhibitors or SSRIs. Still, others seemed to meet the qualifications, but were minimally dosed in some of their prior medication treatments. Categorizing these individuals as truly treatment-resistant is debatable.
“We concluded, therefore, that the trial design should be opened to include any patient that has failed at least one medication effort. If the subject has only been treated with SSRIs, he or she will be treated with one trial protocol. This group will receive either Venlafaxine XR, the medication that showed the greatest treatment success for SSRI non-responders in the STAR*D study, or a rEEGSM guided treatment.
“If, however, the patient has been previously treated with more than the SSRI medication class, then he or she will be treated with another trial protocol. This group will get either STAR*D guided medication in a defined treatment algorithm or rEEGSM recommended treatment.
“As a result, we will have two groups of patients in the study. One group will be those that have only received SSRIs as previous treatment. The second group of patients will be those who have failed multiple medication classes.
“Clearly this has been a learning experience for all involved. To our knowledge there has not been a trial that attempts to compare different treatment algorithms in such a thorough way. We feel strongly that the new design will uphold the validity of the study, while making the processes easier to implement and the results more meaningful. The ability to further leverage this effort with a second study group we hope will provide a robust analysis of rEEGSM contribution to depression treatment.”
About CNS Response
CNS Response is a life-sciences data company focused on the commercialization of the first patented commercial system that guides psychiatrists and other physicians to determine proper treatments for patients with behavioral (mental or addictive) disorders. This technology allows CNS Response to create and provide simple reports (“rEEGSM Reports”) that specifically guide physicians to treatment strategies based on the patient’s own physiology.
rEEGSM utilizes traditional electroencephalography (EEG) in conjunction with a normative database and a proprietary clinical (symptomatic) database to identify the following: (1) medication classes most likely to be needed; and (2) medications within these classes with the most probable treatment potential for each patient. Reports are provided to physicians in a relationship analogous to that of a reference laboratory. Prospective, retrospective and field studies of treatment-resistant patients have reported treatment success of 70% or greater in managed care, outpatient psychiatric and residential substance abuse clinical settings.
In addition to providing analytical support to physicians, CNS Response is also an aide to pharmaceutical developers, who can use rEEGSM to (1) stratify study populations to improve the success of FDA clinical trials; (2) provide insight on effective therapeutic dosing of investigational drugs; (3) identify additional indications for psychiatric medications; (4) provide insight into effective drug combinations; and (5) discover opportunities for decision analytics and support. In addition to these applications, CNS Response continues to investigate the use of rEEG analysis for development of proprietary pharmaceutical opportunities.
Safe Harbor Statement Under the Private Securities Litigation Reform Act
of 1995
Except for the historical information contained herein, the matters discussed are forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, as amended. These statements involve risks and uncertainties as set forth in the Company’s filings with the Securities and Exchange Commission. These risks and uncertainties could cause actual results to differ materially from any forward-looking statements made herein.
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CONTACT: media, Janine McCargo, +1-646-536-7033,
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sephraim@theruthgroup.com, all for CNS Response, Inc.
