scholarly journals Clinical Translation of Cell Therapies in Stroke (CT2S) Checklist—a pragmatic tool to accelerate development of cell therapy products

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anjali Nagpal ◽  
Austin G. Milton ◽  
Simon A. Koblar ◽  
M. Anne Hamilton-Bruce
Keyword(s):  
Health Economic ◽  
Cell Therapy ◽  
Study Design ◽  
Early Phase ◽  
Research Output ◽  
Phase Cell ◽  
Cell Therapies ◽  
Stroke Research ◽  
Data Elements ◽  
The Impact

Abstract Background Cell therapies present an exciting potential but there is a long history of expensive translational failures in stroke research. Researchers engaged in cell therapy research would benefit from a practical framework that can help in planning research and development of investigational cell therapies into viable medical products. Methods We developed a checklist using a mixed methodology approach to evaluate the impact of study design, regulatory policy, ethical, and health economic considerations for efficient implementation of early phase cell therapy studies. Results The checklist comprises a series of questions arranged under four domains: the first concerns study design such as characterization of target study population, trial design, endpoints and operational fit of dosage, time, and route of administration to target populations. A second domain addresses the data package required for regulatory approval relevant to the intended use (allogeneic/autologous; homologous/non-homologous; nature of cell processing). The third domain comprises patient involvement to ensure relevant data is collected via targeted study design. The final domain requires the team to determine the critical data elements that could be built into study design to enable health economic data collection to be started at an early phase of the study. Conclusions The CT2S checklist can help to determine areas of expertise gaps and enable research groups to appropriately allocate resources for capacity building. Use of this checklist will allow identification of key areas where trial planning needs to be optimized, as well as helping to identify resources that need to be secured. The CT2S checklist can also serve as a general cell therapy research decision aid to improve research output and accelerate new cell therapy development.

scholarly journals PERSPECTIVES: Stroke survivors' views on the design of an early‐phase cell therapy trial for patients with chronic ischaemic stroke

2019 ◽  
Vol 22 (5) ◽  
pp. 1069-1077 ◽  
Author(s):  
Anjali Nagpal ◽  
Susan Hillier ◽  
Austin G. Milton ◽  
Monica A. Hamilton‐Bruce ◽  
Simon A. Koblar
Keyword(s):  
Cell Therapy ◽  
Ischaemic Stroke ◽  
Early Phase ◽  
Phase Cell ◽  
Stroke Survivors ◽  
Therapy Trial

scholarly journals A few ethical issues in translational research for gene and cell therapy

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Luciana Riva ◽  
Carlo Petrini
Keyword(s):  
Gene Therapy ◽  
Cell Therapy ◽  
Translational Research ◽  
Early Phase ◽  
Ethical Issues ◽  
The United States ◽  
Cell Therapies ◽  
Biomedical Technologies ◽  
Regulatory Approach ◽  
Gene And Cell Therapy

Abstract Background Although translational research for drug development can provide patients with valuable therapeutic resources it is not without risk, especially in the early-phase trials that present the highest degree of uncertainty. With the extraordinary evolution of biomedical technologies, a growing number of innovative products based on human cells and gene therapy are being tested and used as drugs. Their use on humans poses several challenges. Methods In this work, we discuss some ethical issues related to gene and cell therapies translational research. We focus on early-phase studies analysing the regulatory approach of Europe and the United States. We report the current recommendations and guidelines of international scientific societies and European and American regulatory authorities. Results The peculiarity of human cell- or tissue-based products and gene therapy has required the development of specific regulatory tools that must be continually updated in line with the progress of the research. The ethics of translational research for these products also requires further considerations, particularly with respect to the specificity of the associated risk profiles. Conclusions An integrated ethical approach that aims for transparency and regulation of development processes, the support of independent judgment in clinical trials and the elimination of unregulated and uncontrolled grey areas of action are necessary to move gene and cell therapy forward.

scholarly journals What are potential barriers and enablers to patient and physician participation in Canadian cell therapy trials for stroke? A stakeholder interview study

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e034354
Author(s):  
Manoj M Lalu ◽  
Madison Foster ◽  
Justin Presseau ◽  
Dar Dowlatshahi ◽  
Gisell Castillo ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Therapy ◽  
Early Phase ◽  
Controlled Trial ◽  
Theoretical Domains Framework ◽  
Interview Study ◽  
Chronic Stroke ◽  
Phase Cell ◽  
Potential Barriers ◽  
Barriers And Enablers

ObjectivesEarly phase cell therapy trials face many barriers to successful, timely completion. To optimise the conduct of a planned clinical trial of mesenchymal stem cell (MSC) therapy for chronic stroke, we sought patient and physician views on possible barriers and enablers that may influence their participation.DesignSemistructured interview study.SettingPatients were recruited from three rehabilitation centres in Ontario, Canada; physicians were recruited from across Canada through snowball sampling.ParticipantsThirteen chronic stroke patients (patients who had experienced a stroke at least 3 months prior; 10 male, 3 female) and 15 physicians (stroke physiatrists; 9 male, 6 female) participated in our interview study. Data adequacy was reached after 13 patient interviews and 13 physician interviews.MethodsInterview guides and directed content analysis were based on the Theoretical Domains Framework (TDF). Interviews were coded, and relevant themes were identified.ResultsMost patients were optimistic about participating in an MSC therapy clinical trial, and many expressed interest in participating, even if it was a randomised controlled trial with the possibility of being allocated to a placebo group. However, the method of administration of cells (intravascular preferred to intracerebral) and goal of the trial (efficacy preferred to safety) may influence their intention to participate. All physicians expressed interest in screening for the trial, though many stated they were less motivated to contribute to a safety trial. Physicians also identified several time-related barriers and the need for resources to ensure feasibility.ConclusionsThis novel application of the TDF helped identify key potential barriers and enablers prior to conducting a clinical trial of MSC therapy for stroke. This will be used to refine the design and conduct of our trial. A similar approach may be adopted by other investigators considering early phase cell therapy trials.

Developing Cell Therapies: Enabling cost prediction by value systems modeling to manage developmental risk.

2013 ◽  
Vol 19 (2) ◽  
Author(s):  
Mark Joseph McCall ◽  
David John Williams
Keyword(s):  
Cell Therapy ◽  
New Product Development ◽  
Phase 1 ◽  
Discrete Event ◽  
Latin Hypercube Sampling ◽  
Value Systems ◽  
Phase 2 ◽  
Financial Reports ◽  
Cell Therapies ◽  
The Impact

This work quantifies the highest risk activities and interdependencies in cell therapy new product development (NPD).  A simulation model based upon an activates based and information driven  approach of the Design Structure Matrix (DSM), using Latin Hypercube sampling methods with discrete event simulation evaluated the interdependencies between critical development tasks.  Input data was collected from quarterly financial reports of cell therapy developers and developmental milestones as reported in company press releases and publications.  . Successfully planning and managing development processes is problematic in an emerging industry lacking precedents and standardised technology platforms.   Methods of understanding and reducing developmental uncertainty and risk are needed to aid resourcing decisions.  A particular requirement is to understand the impact of process and clinical development, in this highly regulated sector. Results from the model quantify the probability and impact of process iterations and failures that impact cost and duration of cell therapy NPD.  High impact areas quantified are the interdependence of Phase 1 clinical trials and investment, the scaling of the manufacturing process from Phase 1 to Phase 2 and Phase 2 to Phase 3.  The model also allows for the calculation of the probability of NPD success for given resource levels, time constraints and market conditions.  An application comparing alternative regulatory approaches indicates that the current favoured strategy of targeting an orphan indication gives little benefit for the tested clinic al indication because of reduced clinical trial recruitment rate.  While specifically developed for cell therapy NPD this modelling approach has potential application across the wider biotechnology industry.

scholarly journals Cell Therapies for Spinal Cord Injury: Trends and Challenges of Current Clinical Trials

Neurosurgery ◽  
2020 ◽  
Vol 87 (4) ◽  
pp. E456-E472
Author(s):  
Richard D Bartlett ◽  
Sarah Burley ◽  
Mina Ip ◽  
James B Phillips ◽  
David Choi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Cell Therapy ◽  
Early Phase ◽  
Basic Research ◽  
Great Promise ◽  
Cell Therapies ◽  
Human Spinal Cord ◽  
Cord Injury

Abstract Cell therapies have the potential to revolutionize the treatment of spinal cord injury. Basic research has progressed significantly in recent years, with a plethora of cell types now reaching early-phase human clinical trials, offering new strategies to repair the spinal cord. However, despite initial enthusiasm for preclinical and early-phase clinical trials, there has been a notable hiatus in the translation of cell therapies to routine clinical practice. Here, we review cell therapies that have reached clinical trials for spinal cord injury, providing a snapshot of all registered human trials and a summary of all published studies. Of registered trials, the majority have used autologous cells and approximately a third have been government funded, a third industry sponsored, and a third funded by university or healthcare systems. A total of 37 cell therapy trials have been published, primarily using stem cells, although a smaller number have used Schwann cells or olfactory ensheathing cells. Significant challenges remain for cell therapy trials in this area, including achieving stringent regulatory standards, ensuring appropriately powered efficacy trials, and establishing sustainable long-term funding. However, cell therapies hold great promise for human spinal cord repair and future trials must continue to capitalize on the exciting developments emerging from preclinical studies.

The impact of age on the outcome of cardiac cell therapy

2010 ◽  
Vol 58 (S 01) ◽  
Author(s):  
B Nasseri ◽  
M Kukucka ◽  
SJ Kim ◽  
YH Choi ◽  
KS Kang ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Cardiac Cell ◽  
Cardiac Cell Therapy ◽  
The Impact

Exploring power in response inhibition tasks using the bootstrap: The impact of number of participants, number of trials, effect magnitude, and study design

2019 ◽  
Author(s):  
Curtis David Von Gunten ◽  
Bruce D Bartholow
Keyword(s):  
Study Design ◽  
Effect Size ◽  
Statistical Power ◽  
Bootstrap Sampling ◽  
Reliable Measure ◽  
Internal Reliability ◽  
The Impact ◽  
Power Analyses ◽  
Effect Magnitude

A primary psychometric concern with laboratory-based inhibition tasks has been their reliability. However, a reliable measure may not be necessary or sufficient for reliably detecting effects (statistical power). The current study used a bootstrap sampling approach to systematically examine how the number of participants, the number of trials, the magnitude of an effect, and study design (between- vs. within-subject) jointly contribute to power in five commonly used inhibition tasks. The results demonstrate the shortcomings of relying solely on measurement reliability when determining the number of trials to use in an inhibition task: high internal reliability can be accompanied with low power and low reliability can be accompanied with high power. For instance, adding additional trials once sufficient reliability has been reached can result in large gains in power. The dissociation between reliability and power was particularly apparent in between-subject designs where the number of participants contributed greatly to power but little to reliability, and where the number of trials contributed greatly to reliability but only modestly (depending on the task) to power. For between-subject designs, the probability of detecting small-to-medium-sized effects with 150 participants (total) was generally less than 55%. However, effect size was positively associated with number of trials. Thus, researchers have some control over effect size and this needs to be considered when conducting power analyses using analytic methods that take such effect sizes as an argument. Results are discussed in the context of recent claims regarding the role of inhibition tasks in experimental and individual difference designs.

scholarly journals The impact and cost‐effectiveness of community‐basedHIVself‐testing in sub‐Saharan Africa: a health economic and modelling analysis

2019 ◽  
Vol 22 (S1) ◽  
pp. e25243 ◽  
Author(s):  
Valentina Cambiano ◽  
Cheryl C Johnson ◽  
Karin Hatzold ◽  
Fern Terris‐Prestholt ◽  
Hendy Maheswaran ◽  
...  
Keyword(s):  
Health Economic ◽  
Cost Effectiveness ◽  
Sub Saharan Africa ◽  
Modelling Analysis ◽  
Sub Saharan ◽  
The Impact

scholarly journals The impact of non-pharmaceutical interventions on COVID-19 epidemic growth in the 37 OECD member states

2021 ◽  
Author(s):  
Francisco Pozo-Martin ◽  
Heide Weishaar ◽  
Florin Cristea ◽  
Johanna Hanefeld ◽  
Thurid Bahr ◽  
...  
Keyword(s):  
Growth Rate ◽  
Early Phase ◽  
Policy Decision ◽  
Multilevel Modelling ◽  
Daily Growth ◽  
Public Places ◽  
Member States ◽  
Unit Increase ◽  
Policy Decision Making ◽  
The Impact

AbstractWe estimated the impact of a comprehensive set of non-pharmeceutical interventions on the COVID-19 epidemic growth rate across the 37 member states of the Organisation for Economic Co-operation and Development during the early phase of the COVID-19 pandemic and between October and December 2020. For this task, we conducted a data-driven, longitudinal analysis using a multilevel modelling approach with both maximum likelihood and Bayesian estimation. We found that during the early phase of the epidemic: implementing restrictions on gatherings of more than 100 people, between 11 and 100 people, and 10 people or less was associated with a respective average reduction of 2.58%, 2.78% and 2.81% in the daily growth rate in weekly confirmed cases; requiring closing for some sectors or for all but essential workplaces with an average reduction of 1.51% and 1.78%; requiring closing of some school levels or all school levels with an average reduction of 1.12% or 1.65%; recommending mask wearing with an average reduction of 0.45%, requiring mask wearing country-wide in specific public spaces or in specific geographical areas within the country with an average reduction of 0.44%, requiring mask-wearing country-wide in all public places or all public places where social distancing is not possible with an average reduction of 0.96%; and number of tests per thousand population with an average reduction of 0.02% per unit increase. Between October and December 2020 work closing requirements and testing policy were significant predictors of the epidemic growth rate. These findings provide evidence to support policy decision-making regarding which NPIs to implement to control the spread of the COVID-19 pandemic.

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