A Multi-Stakeholder Perspective On Assessing Drug Value

VeraSci’s VP of Regulatory Strategy and Market Access Innovation and former AIFA Director, Dr. Luca Pani, participated in the Boston Consulting Group (BCG) Market Access Roundtable and recently published a paper discussing the variables and challenges involved in the assessment of drug value.

After decades of decline, the industry pipeline of approved products has rebounded1 over the last five years and in 2018, 59 new drugs were approved by FDA, the highest number in history. This includes 19 (32%) novel drugs approved as first in class. More than half of the new drugs (34 out of 59) were approved to treat rare or orphan disease.2 These innovative drugs enter into constrained healthcare systems that struggle to cope with demographic change and complex incentive and payment systems. While patients demand fast access to these new treatment options, payers are forced to make trade-offs in allocating their constrained budgets.

There is broad consensus that a focus on “value” is the appropriate approach for optimizing spend of constrained healthcare resources. By focusing on value, payers aim to optimally and equitably allocate constrained resources to areas of greatest need and to treatments with greatest impact on patients and healthcare systems. However, value assessments are not only about the equitable allocation of resources and funding, but also need to cover the creation of appropriate rewards to spur innovation.

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Virtual reality assessment of functional capacity in people with Schizophrenia: Associations with reduced emotional experience and prediction of functional outcomes

Virtual Reality (VR) approaches have had considerable success in measurement of functional capacity. However, it is not clear if factors other than cognitive impairment influence performance on VR measures. Many people with schizophrenia have significant negative symptoms and they could reduce engagement in assessment. 158 patients with schizophrenia performed the VRFCAT, were tested with the MCCB, were rated with the PANSS, and were rated on everyday functioning. Scores for reduced emotional experience and reduced expression were derived. Reduced emotional experience, but not reduced expression, was correlated with socially relevant VRFCAT subtasks and real-world social functioning. Performance on the socially relevant subtasks, but not the solitary subtasks, shared variance with work outcomes. MCCB performance was associated with both subdomains, but socially relevant subtasks shared more variance. Patients with higher reduced emotional experience validly engaged in socially relevant VR simulations, as indexed by correlations with outcome measures. These patients had poorer performance on socially relevant tasks than on solitary tasks. The differential validity of solitary vs. socially relevant simulations was supported by differences in correlates, suggesting that assessments with a focus on performance of simulated socially relevant tasks could be developed.

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The Endless Frontier? The Recent Upsurge of R&D Productivity in Pharmaceuticals

Classical analyses of pharmaceutical pipelines from 1990 to 2010 reported increasing attrition rates and duration of clinical trials, leading to a perception of a “productivity crisis” in this sector. However, in contrast, a more recent analysis of over 45,000 projects in the last decade completed by VeraSci’s Dr. Luca Pani and colleagues showed an upsurge in R&D Productivity. This result is largely driven by two factors: company efficiency – in particular aborting studies in early phases – and concentration on high yield projects. The number of new advanced therapy projects are at an all-time high and time to market from initial IND is at an all-time low. This combination will put additional pressure on regulators and payers world-wide. It is therefore essential that sponsors are fully prepared to interact with regulators and payers efficiently and productively. VeraSci’s Regulatory Strategy and Market Access Innovation team led by Dr. Pani can greatly facilitate those interactions.

Article is no longer available. Please contact VeraSci for more information.

Virtual reality assessment of functional capacity in the early course of schizophrenia

Computer-based virtual reality assessments of functional capacity have shown promise as a reliable and valid way to assess individuals with multi-episode schizophrenia. However, there has been little research utilizing this innovative approach with young patients who are in the early phase of schizophrenia.

VeraSci’s proprietary Virtual Reality Functional Capacity Assessment Tool (VRFCAT) integrates virtual reality into the assessment of functioning in clinical trials. The VRFCAT is administered on a computer or our tablet-based platform, Pathway, and simulates key instrumental activities of daily living (iADLS) in a realistic and interactive virtual environment. With demonstrated sensitivity to basic functional capacity deficits, the VRFCAT was developed to improve clinical trials by detecting functionally meaningful improvements in patients’ everyday lives. The VRFCAT has numerous advantages over conventional assessments, and meets the highest psychometric and regulatory standards, with strong support from industry sponsors, NIH and FDA as a functional co-primary outcome measure.

A recently published manuscript by Ventura et al., including as a co-author VeraSci’s CEO and Co-founder Dr. Richard Keefe, extended previous findings to patients with first-episode schizophrenia. Virtual-reality–based performance was correlated with a standard test of functional capacity, indicating VRFCAT validity. Furthermore, correlations with cognitive functioning and occupational/school and social functioning indicate promise as a coprimary measure to track changes in response to treatment.

CLICK HERE to read the full manuscript: Virtual reality assessment of functional capacity in the early course of schizophrenia: Associations with cognitive performance and daily functioning by
Joseph Ventura, Tamara Welikson, Arielle Ered, Kenneth L. Subotnik, Richard S. E. Keefe, Gerhard S. Hellemann, Keith H. Nuechterlein. Early Intervention in Psychiatry. 2019;1–9.

Comprehensive review of the research employing the schizophrenia cognition rating scale (SCoRS)

Schizophrenia Cognition Rating Scale

The Schizophrenia Cognition Rating Scale (SCoRS) is a 20-item interview-based clinical assessment that evaluates cognitive deficits and the degree to which these deficits impair patients’ day-to-day functioning. It was originally developed in 2001 at Duke University Medical Center by VeraSci CEO and Co-Founder Dr. Richard Keefe and is licensed through VeraSci. The SCoRS is used in registration-level clinical trials, academic research and in clinical settings. The SCoRS contains questions about the patient’s ability to manage cognitively demanding, functionally relevant, everyday tasks.

The SCoRS items were developed to assess the following cognitive domains:• Attention

  • Memory
  • Working Memory
  • Language Production
  • Reasoning
  • Problem Solving
  • Motor Skills
  • Social Cognition

A recently published manuscript: Comprehensive review of the research employing the schizophrenia cognition rating scale (SCoRS) by Philip D. Harvey, Anzalee Khan, Alexandra Atkins, Trina M. Walker, Richard S.E. Keefe is a review of research utilizing the SCoRS that outlines the development, evaluation, validation, and implementation of the SCoRS to assess whether the scale meets the criteria as a functional co-primary measure as defined by the MATRICS-CT initiative.

The MATRICS-CT initiative was developed by the NIMH in conjunction with industry and FDA partners to offer a systematic translation (T) of the MATRICS consensus cognitive assessment battery (MCCB) and to develop a co-primary (C) measure of outcomes for clinical trials. This publication addresses the appropriateness of the SCoRS as a co-primary measure and its global applicability.

Interview-based co-primary assessments should be: 1) practical and easy to administer for a clinician or researcher; 2) validated in individuals with schizophrenia; 3) contain the relevant areas of cognition and functioning applicable to schizophrenia; 4) able to assess all phases and severity levels of schizophrenia; 5) capable of monitoring disease progression; 6) minimal burden to patients; and 7) sensitive to assess treatment effects. A review of the literature was conducted to present information on the development, psychometric properties and usage of the SCoRS. Review of the development of the SCoRS followed the parameters outlined for scale development on content expert validation and feedback.

The SCoRS shows good psychometric properties in various studies and demonstrates low burden on clinicians and patients. The items measure global concepts that do not require notable cultural modification, making international use feasible. While multiple performance-based tests in cognition and functional outcomes are available, there is a need for a multi-domain, interview-based assessment of cognitive progression and treatment response in clinical trials. The SCoRS appears to meet many of the criteria for an optimal co-primary measure for schizophrenia cognition clinical trials as defined in the MATRICS-CT initiative.

To read the full publication in Schizophrenia Research: Comprehensive review of the research employing the schizophrenia cognition rating scale (SCoRS) by Philip D. Harvey, Anzalee Khan, Alexandra Atkins*, Trina M. Walker*, Richard S.E. Keefe* CLICK HERE

Note: * VeraSci Leadership

Regulatory issues related to Attenuated Psychosis Syndrome (APS) and Schizophrenia

A recently published manuscript in the Journal Schizophrenia Research by Dr. Luca Pani and Dr. Richard Keefe of VeraSci provides an overview of the regulatory and policy issues related to the treatment of CNS disorders, with a focus on attenuated psychosis syndrome (APS) and schizophrenia. Schizophrenia has undergone a reconceptualization as a psychotic spectrum disorder, rather than a progressive or continuum disorder such as Alzheimer’s Disease or Parkinson’s Disease that follow a pattern of increasing severity over time. The current diagnostic and statistical manual (DSM-5) classification of schizophrenia as a spectrum disorder has been accepted as a welcome change from DSM-IV because it reflects the genetic and neurobiological relationship between schizophrenia, schizoaffective disorder, and schizotypal personality disorder. This conceptualization also considers the clinical manifestations of being at risk for psychosis, referred to as the attenuated psychosis syndrome, or APS.

The increased focus on the prodromal stages of schizophrenia is placing increased pressure on the regulatory system. APS represents one of the earliest manifestations of the psychosis spectrum, and regulators are now realizing the importance of therapies that target these initial stages. The subsequent interest in biomarkers for the identification of patients with prodromal CNS disease is essential; however, it can be challenging due to the various molecular and environmental complexities involved. To guide treatment, regulators would prefer biomarkers linked to a drug mechanism of action and disease neurobiology to allow a disease-modifying claim within the product label. In addition, the European Medicines Agency has recently highlighted a need for the co-development of biomarkers alongside corresponding assays that can be successfully transitioned into clinical practice.

There are no approved medications for APS, and there is no established regulatory standard for the conduct of clinical trials in this area. Research into the accurate and sensitive inclusion of individuals within clinical trials, and the conduct of such trials within the global regulatory environment, requires further consideration. Moving forward, translational science should be applied to regulatory concepts and measures, and it is essential that regulatory guidelines are followed for the certification of such measures. Finally, digital technologies that enable active measurement of key endpoints in both clinical trials and real-world settings will shortly be available, paving the way for a new era in patient identification and monitoring.

Read the full Schizophrenia Research: Cognition article, Approaches to attenuated psychosis syndrome treatments: A perspective on the regulatory issues, here.