isctm « ISCTM | The International Society for CNS Clinical Trials and Methodology

Overall objective: Generate a consensus document addressing methodological challenges of international CNS clinical trials.

CNS drug development has become internationally driven and implemented. As a result, new scientific, regulatory, cultural, and operational complexities need to be considered for successful outcomes. In our first two meetings, we gathered input from attendees regarding their greatest concerns for international clinical trials, and decided to focus on the processes for translation and cultural adaptation and harmonization of outcome measures for global clinical trials. The specific stated objective of the group is to establish best practice guidelines on the translation and cultural adaptation of Clinician Reported Outcomes with the ultimate goal of minimizing the impact of culture in clinical trials. We have produced an outline of a manuscript devoted to this topic, and a reading list has been generated and distributed to working group participants. We plan to hold a mid-summer conference call to discuss the reading list, manuscript outline, and to prepare an agenda for the Autumn Working Group Dinner in Boston.

Autumn 2014 Workshop: Cognitive and Functional Assessment in Clinical Trials of Alzheimer’s Disease and Its Precursors: Readying for Short-Term and Long Term Clinical Trial Needs

The goals of this working group continue to be further understanding the challenges in assessing for meaningful improvement or decrement in cognition and / or function during the 6 month to 2 year period of a typical clinical trial of AD and its precursors. At this meeting we will also seek to hear from new sources about assessments that are currently in development. And, to bring in the perspective of Regulators and Payers as well as of a Clinical Trial vs an assessment for a physician evaluating a patient diagnostically.

2014 New Investigator Award: Submission and Eligibility Guidelines

Introduction: The International Society for CNS Clinical Trials and Methodology has created a program to recognize promising new investigators across the broad range of methodological, regulatory and substantive programmatic interests of the society. Up to one international and four (4) domestic NI Award applicants will be selected each year. Appointments as NI Awardees will be for one year. (View Previous Awardees)

Eligibility: Early career (second-year or beyond postdocs or those within 8 years of the completion of training) academic or industry professionals in relevant disciplines and positions; research fellows in CNS disciplines (psychiatry, neurology, neurosurgery, sleep disorders, pain management) and postdoctoral trainees in biostatistics, epidemiology, pharmacy, nursing, public health, and social/behavioral sciences; translational scientists with interest in biomarker-based approaches to treatment development.

Application Requirements: Applicants will submit a poster abstract (ISCTM Poster Guidelines) based on original research in the field of CNS Trial Methodology for which the applicant will serve as presenting author; a one page statement of research and career interests; a complete CV; and one letter of reference. Applications will be due on or before 15 November 2013. Review and selection will be completed no later than 16 December 2013, to allow for participation in the ISCTM 10th Annual Scientific Meeting to be held 18-20 February 2014, in Washington D.C. Link to application form is found at the bottom of this page.

(1) Fee-waived registration for the 10th Annual Scientific Meeting
18-20 February 2014
Washington, DC

(3) A stipend of up to $750 (domestic) and $1,250 (international-outside North America) to defray travel and per diem expenses. Stipends will be available for industry based NI Awardees if company cannot underwrite expenses.

(4) Assignment of ISCTM senior mentor for meeting and for possible interaction beforehand on development of poster.

(B) Opportunity to present poster to senior investigators in the “Poster Rounds” section of the regular poster session

ISCTM Award Committee:
Barry Lebowitz, PhD, UC San Diego (Chair)
Warachal Faison, MD, Pfizer, Inc. (Co-chair)
Robert Berman, MD, Bristol-Myers Squibb
Rob Lasser, MD, Roche
Maria Lopez-Breshnahan, MD, Pfizer, Inc.
Dawn Velligan, PhD, UTHSCSA
Keith Wesnes, PhD, Bracket

Abuse Liability Potential Working Group Dinner Session

The Abuse Deterrent Formulation Science Meeting: Review of the Recommendations and the Next Steps

In January 2013 FDA issued a Draft Guidance for Industry Abuse-Deterrent Opioids — Evaluation and Labeling. This document laid out FDA’s thinking regarding the types of data required to demonstrate abuse deterrent formulation (ADF) characteristics and the labeling claims that might be granted based on these data. As the FDA has acknowledged abuse deterrent formulations represent a new scientific field and there is much to be learned with regards to the formulations themselves and assessing their effectiveness in reducing opioid drug abuse.

Since the FDA expressed interest in collecting input on this Draft Guidance from academia, industry and governmental experts, an ADF Science Meeting was held in the fall of 2013. The objectives of this meeting were: 1) to provide an open forum enabling discussion and recommendations on the FDA Draft Guidance and 2) to provide an opportunity for presentations by experts addressing the Draft Guidance.

· To overview the FDA Draft Guidance on Abuse Deterrent Opioids – Evaluation and Labeling with the focus on clinical assessment of the ADF approaches

Addressing Methodological Challenges in International CNS Trials Working Group Dinner

Objective: Generate a consensus document addressing methodological challenges of international CNS clinical trials.

– Young versus mature science of measurement (cognition, functional outcomes vs psychosis)

We will be collecting survey data from Autumn Conference Workshop attendees, reporting back this information, and establishing a focused agenda with specific discussion points at the Annual Meeting in DC on February 18.

Dementia: Study Designs, Methodologies and Regulatory Perspectives – One Size Does Not Fit All!

Over the last few years there has been increasing concern about the lack of success of drug candidates in clinical trials in Alzheimer’s dementia and mild cognitive impairment. On a more positive note there has been more interest in conducting trials in other types of dementia as well as moving earlier in the AD process.

► What are the similarities and differences when designing clinical trials in various dementia sub-types

► The design of “preclinical” trials (e.g., DIAN, A4, Alzheimer’s Prevention Initiative)

► The value of biomarkers (neuroimaging, CSF etc), genotypes and polymorphisms in identifying relevant patient populations and then enabling a read out in early phase clinical trials

Dementia sub-types, Alzheimer’s disease, vascular, mixed, frontotemporal (FTD), Lewy Body (DLB), and Parkinson’s (PDD) differ in important aspects. For example aetiology and pathophysiology, assessment of background pathology (Parkinson’s disease and parkinsonism in FTD, DLB, PDD), background treatments, choice of scales and primary and secondary endpoints effect size on cognitive endpoints, Inclusion / exclusion criteria, role of neuroimaging and other biomarkers for diagnosis and as an outcome variable and “Regulatory Path”.

From a regulatory perspective the focus of the outcome measures in the first guidelines was on cognition and functioning. More recently we have seen the emergence of guidelines for early dementia and broader thinking around study designs for proof of concept and pivotal studies for drugs with potential to delay progression of the dementias.

This session will explore the lessons learned from experience to date and how that informs, or not, study designs in other dementias and future research. A speaker form the Industry will give a perspective on pathobiological targets or factors not yet addressed in trials in AD dementia. Regulatory agencies from the US and Europe will give their thoughts clinical trial methodology.

Adaptive Design Working Group Dinner Session

There are multiple challenges in the design of comparative effectiveness studies including selecting endpoints, comparator(s), and study population(s). These studies may be larger and longer than placebo-controlled Phase III trials, requiring substantial investment for the study sponsor. Additionally, limited comparative information may be available at the time of protocol development on which to base the decision on endpoints, comparator(s) and study population(s). The ISCTM Adaptive Design Working Group will discuss the issues associated with these decisions and explore the use of multiple adaptations within a single Phase IIIB/IV comparative effectiveness study in schizophrenia.

Implementing Innovation Working Group Dinner Session

The working group aims to deliver a paper with recommendations to help those seeking to implement innovation in CNS drug development. Members have been working to establish a common knowledge-base regarding innovation from other fields and offering feedback to those engaged in innovative initiatives. This dinner session builds on the working groups effort to identify opportunities and challenges to implementing innovation in CNS trials. The primary goals for this dinner will be to complete an initial outline of the group’s paper and to summarize our current working knowledge-base.

2014 ISCTM Research-to-Policy Forum: Revitalizing Academia-Industry Collaboration in Psychiatry Treatment Research

Chairs: Reuven Ferziger, MD; Ronald Manderscheid, PhD

Historically the pipeline between discovering potential new treatments and making new treatments available to patients has benefited from robust scientific interaction between industry, academia and government. In recent years, these interactions have become increasingly complex. Many observers have related the dampening of industry-academia collaboration to the decline in the number of innovative new drugs developed annually. An important factor affecting scientific collaboration has been greatly heightened concern about the ethical and legal standards observed in these relationships. Over the last decade, psychiatric diseases have been at once one of the slowest areas of drug innovation and one of the most frequently identified areas of ethical concern and legal action. A growing number of initiatives are providing frameworks to stimulate industry-academia collaboration while maintaining legal and ethical boundaries. But it has been much easier to do this in “pre-competitive space,” at the more upstream, basic research end of the pipeline, than downstream, at the clinical research and patient care end of drug development.

In Part 1 of this year’s ISCTM Policy Forum, leaders from academia, industry, government and journalism will describe the problems constraining academia-industry collaboration and paths bring pursued to optimize collaboration. In Part 2, the speaker panel and the audience will be presented with cases that both encourage and challenge opportunities for academia-industry collaboration. The cases will focus on downstream research on psychiatric diseases and treatments. The case discussions will be moderated to encourage audience participation.

The Forum will begin with keynote remarks by Jeffrey Lieberman, President of the American Psychiatric Association. Case discussions will be moderated by Howard Goldman (Editor, Psychiatric Services). Invited speakers include Richard Frank (HHS Deputy Secretary Nominee), Freda Lewis Hall (Chief Medical Officer, Pfizer).

Registration for the Forum Only session is complimentary.

Domain-Based Approaches to Pathology in the Development of Novel Psychiatric Therapies: Enhancing Tractability in Discovery and Trial Methodology

Clinical Trials in CNS have traditionally included patients based upon criteria from the Diagnostic and Statistical Manual (DSM) and International Classification of Diseases (ICD). These diagnostic entities include heterogeneous populations that, most likely, do not share a common biology. Findings from various scientific disciplines – including genetics, neurobiology, neural circuitry, neuroanatomy, neuroscience, and neuropsychology have repeatedly demonstrated that the underlying pathology of major psychiatric disorders does not abide by the discrete entities of our classification systems. Instead, pathological neurobiology and behavior are more parsimoniously explained by symptom clusters that traverse diagnostic entities. These findings and these approaches raise the question of the relative value of symptom domains as treatment targets as opposed to traditional DSM and ICD diagnoses in CNS clinical trials. In order to develop treatments that will more likely address the underlying neurobiology of psychiatric disorders, a more sensitive and efficient approach will be to design methods and outcomes that align with the structure of CNS pathology as it exists in the population.

This session will address a series of questions that arise in the consideration of the use of domain-based approaches to pathology in the development of novel psychiatry therapies.

Q1: What are the domain-based approaches? Why do we believe this approach would enhance tractability in therapy development? What are the short and long-term implications on neuroscience R&D

Q2: What is the biological plausibility of the different symptom domains? What are the possible neural substrates underlying these symptom domains? Are these substrates consistent across disease states and diagnoses? Do these substrates translate from animals to healthy individuals to patients?

Q3: What is the dimensional expression of the different symptom domains across clinical diagnoses? Are these domains measurable? What are the different psychometric properties needed to evaluate the severity of symptom domains in patients with different psychiatric or neurologic conditions?

Q4: What are the pathways for drug development using the symptom-based approach? What are the regulatory approaches? Will payers adopt their value models to integrate the symptom-based approach?

Four speakers will address these questions from various perspectives, including leaders from industry and academia who are implementing trials with a domain-based focus. Cognition and motivation will be used as models due to advances in understanding the biology, psychometrics, and functional relevance of impairment across different diagnostic entities, and the potential applicability of animal models. Following the four presentations, representatives from US and European regulatory agencies and representatives from public and private payer institutions will be asked to comment on the potential implications of domain-based approaches on policy. The goal will be to understand the value of these approaches for patients and how to integrate them in regulatory guidelines.

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Autumn 2014 Workshop: Addressing Methodological Challenges in International CNS Trials Working Group