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.

 

 

Development of a Patient-Reported Outcomes Symptom Measure of Patients with Non-Transfusion-Dependent Thalassemia (NTDT-PRO ©)

Ali Taher 1 | Vip Viprakasit 2 | Maria Domenica Cappellini 3 | Pranee Sutcharitchan 4 |Richard Ward 5 | Dalia Mahmoud 6 | Abderrahmane Laadem 6 | Anzalee Khan 7,8 |Chad Gwaltney 9 | Gale Harding 10 | Kenneth Attie 11 | Xiaosha Zhang 11 | Jun Zou 6 | Joseph Pariseau6 | X. Henry Hu 6† | Antonis Kattamis 12

Abstract
β-Thalassemia, a hereditary blood disorder caused by reduced or absent synthesis of the β-globin chain of hemoglobin, is characterized by ineffective erythropoiesis, and can manifest as nontransfusion-dependent thalassemia (NTDT) or transfusion-dependent thalassemia (TDT). Many patients with NTDT develop a wide range of serious complications that affect the survival and quality of life (QoL). Patient-reported outcomes (PRO), including health-related QoL (HRQoL), are important tools for determining patient health impairment and selecting appropriate treatment. However, there are currently no disease-specific PRO tools available to assess symptoms related to chronic anemia experienced by patients with NTDT. This study aimed to develop a new, US Food and Drug Administration (FDA)-compliant PRO of chronic anemia symptoms, the NTDT-PRO© tool, for use in patients with NTDT. Participants had a median age of 36 years (range, 18-47) and 60% were female. The initial development of the NTDT-PRO tool involved concept-elicitation interviews with 25 patients from 3 centers (in Lebanon, Greece, and Canada); subsequent interview discussions and clinical input resulted in the generation of 9 items for inclusion in the draft NTDT-PRO. Following a round of cognitive interviews involving 21 patients from 2 centers (in Lebanon and Greece), 4 items (Pain, Headaches, Ability to Concentrate, and Paleness) were removed from the draft NTDT-PRO. The final NTDT-PRO comprises 6 items that measure Tiredness, Weakness, and Shortness of Breath, with or without Physical Activity. The NTDT-PRO is a new disease-specific HRQoL tool for patients with NTDT, developed using a thorough methodology based on FDA 2009 PRO development guideline.

Follow the link below for the full article:

Taher_et_al-NTDT-PRO Development-2018-American_Journal_of_Hematology

Validation of a Patient-Reported Outcomes Symptom Measure of Patients with Non-Transfusion-Dependent Thalassemia (NTDT-PRO ©)

Ali Taher 1 | Maria Domenica Cappellini 2 | Vip Viprakasit 3 | Pranee Sutcharitchan 4 |Dalia Mahmoud 5 | Abderrahmane Laadem 5 | Anzalee Khan 6,7 | Chad Gwaltney 8 |Gale Harding 9 | Kenneth Attie 10 | Xiaosha Zhang10 | Jun Zou 5 | Joseph Pariseau 5 |X. Henry Hu 5† | Antonis Kattamis 11

Abstract
This study demonstrates the quantitative characteristics of the first patient-reported outcome (PRO) tool developed for patients with nontransfusion dependent β-thalassemia (NTDT), the NTDT-PRO©. A multicenter validation study was performed over 24 weeks, involving 48 patients from Italy, Lebanon, Greece, and Thailand. Most patients were female (68.8%), with a median age
of 34.5 years (range, 18-52); 66.7% were diagnosed with β-thalassemia intermedia, and median time since diagnosis was 22 years (range, 0-43). The NTDT-PRO comprises 6 items across 2 domains (Tiredness/Weakness and Shortness of Breath [SoB]), and was valid and reliable, with good consistency. At baseline, most patients reported symptoms as present via the NTDT-PRO,
and were highly compliant, ≥90% completing the NTDT-PRO tool. In a pairwise correlation analysis, all items were positively correlated. Correlations between NTDT-PRO and existing tools— 36-Item Short Form Health Survey version 2 (SF-36v2) and Functional Assessment of Cancer Therapy-Anemia (FACT-An)—were assessed at weeks 1, 3, and 12; robust correlations were seen between SoB and SF-36v2-Vitality (rs = −0.53), and between SoB and Fact-An-Fatigue Experience (rs = −0.66) at week 1. Internal consistency was high for both Tiredness/Weakness (Cronbach alpha, 0.91) and SoB (Spearman-Brown coefficient, 0.78); intraclass correlation coefficients were high (Tiredness/Weakness, 0.88 and 0.97; SoB, 0.92 and 0.98), demonstrating stability. Further studies are required to fully support the validity of this tool, this study demonstrated the usefulness of the NTDT-PRO in the clinical setting and for longitudinal clinical research, particularly in trials where patient health-related quality of life is expected to change.

Follow the link below for the full article:

Taher_et_al-NTDT-PRO Validation-2018-American_Journal_of_Hematology

Significant Enhancements Announced for Pathway, VeraSci’s Proprietary eCOA Platform

Significant Enhancements Announced for Pathway,

VeraSci’s Proprietary eCOA Platform

Integrating Clinical, Cognitive and Functional Assessments onto one device.

 

Durham, NC—December 6, 2018—VeraSci, a global clinical technology and research services company, announces multiple significant enhancements to Pathway, their proprietary eCOA platform. Pathway, which reinvented how raters, sponsors and site administrators conduct assessments and scales for clinical trials, now offers enhanced data collection and administration, and access to a larger number and type of scales and assessments.

The Pathway team worked with raters, scale-developers, and sponsors to ensure that all Pathway users would derive optimal functionality while accommodating the needs of each study and site. The improved flexibility of Pathway allows for the use of a single device for multiple assessments and multiple protocols, permits high enrolling sites to use different devices for parallel assessment of multiple patients, and easily integrates all of the data. VeraSci’s proprietary assessments, BAC and VRFCAT, and licensed gold standard endpoints and safety measures for multiple therapeutic areas such as the EDSS and C-SSRS, are now accessible through a single Pathway-enabled device. In addition, raters can administer assessments on Pathway and obtain consent from test subjects on the same device.

Available in multiple languages, Pathway is able to accommodate a sponsor’s specific needs for an integrated experience in a variety of countries, with negligible failure rates or device issues. VeraSci’s multi-lingual tech support teams in Europe, Asia, and the United States provide support in sites’ local languages, and VeraSci’s Global Language Solutions team provides scientifically valid translations and cultural adaptations of required assessments.

The feedback from users has been extraordinary. Dave Walling, Ph.D. of CNS Network LLC, explains, “Pathway simplifies the process for raters at the site level by integrating the assessments into one system. Rating on a tablet can often be a frustrating experience as there are multiple log-ins, connection problems, and technological mishaps…Pathway helps to combat those issues and makes the process easier for staff, subjects and ultimately, sponsors”.

If you are interested in learning more about Pathway, an FDA 21 CFR Part 11 Compliant eCOA platform, visit our website; https://verasci.com/what-we-do/our-solutions/pathway/

About VeraSci

Founded in 2004, VeraSci has a worldwide presence in clinical trial development, clinical and cognitive assessment and language services. VeraSci brings deep expertise, strategic innovation and unwavering commitment to every project, allowing each client to deliver data supporting innovative therapies.

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VeraSci is a registered trademark of NCT Holdings in the United States and/or other countries.