Aspects of Investigational Antineoplastic Agents

1991 ◽  
Vol 4 (1) ◽  
pp. 64-71
Author(s):  
Clarence L. Fortner ◽  
Paul J. Vilk
Keyword(s):  
Clinical Trial ◽  
Unique Role ◽  
Investigational Agent ◽  
Institutional Review ◽  
Investigational Drugs ◽  
Consent Document ◽  
Us Government ◽  
Government Work ◽  
Informed Consent Document ◽  
Patient Use

Investigational drugs are regulated by the Food and Drug Administration (FDA) and are not available for widespread patient use. They are screened and evaluated extensively before they are administered to humans in clinical trials. The clinical development process is divided into three phases: phase I, II, and III. Protocols for the investigational agent in each of these phases must be approved by an institutional review board and the patient must be informed of the risks of the study and sign an informed consent document. Once adequate clinical data are collected and analyzed, the information is submitted to the FDA for their review and approval for marketing. Prior to that approval, the FDA may approve broader distribution of the drug for specific indications under a Treatment Investigational New Drug (IND) or the National Cancer Institute's (NCI) group C mechanism. Pharmacists can play a unique role during development of the Treatment IND by contributing to design of the protocol and screening patient qualifications. The investigator of the clinical trial has responsibility for the conduct of the clinical trial and must comply with FDA regulations and sponsor policies. This is a US government work. There are no restrictions on its use.

scholarly journals Informed Consent

2015 ◽  
Vol 06 (03) ◽  
pp. 466-477 ◽  
Author(s):  
F. Manion ◽  
K. Hsieh ◽  
M. Harris ◽  
S. H. Fenton
Keyword(s):  
Informed Consent ◽  
Medical Record ◽  
Health Systems ◽  
Research Process ◽  
Institutional Review ◽  
Consent Document ◽  
Information Governance ◽  
Informed Consent Document ◽  
Computer Based ◽  
Investigative Team

Summary Background: Despite efforts to provide standard definitions of terms such as “medical record”, “computer-based patient record”, “electronic medical record” and “electronic health record”, the terms are still used interchangeably. Initiatives like data and information governance, research biorepositories, and learning health systems require availability and reuse of data, as well as common understandings of the scope for specific purposes. Lacking widely shared definitions, utilization of the afore-mentioned terms in research informed consent documents calls to question whether all participants in the research process — patients, information technology and regulatory staff, and the investigative team — fully understand what data and information they are asking to obtain and agreeing to share. Objectives: This descriptive study explored the terminology used in research informed consent documents when describing patient data and information, asking the question “Does the use of the term “medical record” in the context of a research informed consent document accurately represent the scope of the data involved?” Methods: Informed consent document templates found on 17 Institutional Review Board (IRB) websites with Clinical and Translational Science Awards (CTSA) were searched for terms that appeared to be describing the data resources to be accessed. The National Library of Medicine’s (NLM) Terminology Services was searched for definitions provided by key standards groups that deposit terminologies with the NLM. Discussion: The results suggest research consent documents are using outdated terms to describe patient information, health care terminology systems need to consider the context of research for use cases, and that there is significant work to be done to assure the HIPAA Omnibus Rule is applied to contemporary activities such as biorepositories and learning health systems. Conclusions: “Medical record”, a term used extensively in research informed consent documents, is ambiguous and does not serve us well in the context of contemporary information management and governance. Citation: Fenton SH, Manion F, Hsieh K, Harris M. Informed Consent: Does Anyone Really Understand What Is Contained In The Medical Record? Appl Clin Inform 2015; 6: 466–477http://dx.doi.org/10.4338/ACI-2014-09-SOA-0081

scholarly journals Implementing a New Common Rule Requirement for Informed Consent: A Randomized Trial on Adult Asthma Patients

2019 ◽  
Vol 4 (1) ◽  
pp. 238146831983931
Author(s):  
Michael Yu ◽  
Baruch Fischhoff ◽  
Tamar Krishnamurti
Keyword(s):  
Clinical Trial ◽  
Informed Consent ◽  
Relevant Information ◽  
Full Length ◽  
Enrollment Decisions ◽  
Common Rule ◽  
Consent Document ◽  
Asthma Patients ◽  
Informed Consent Document ◽  
Interactive Version

Objectives. To determine how the format of a clinical trial informed consent document can affect participants’ retention of enrollment-relevant information. Background. Recent changes to the US Federal Common Rule require informed consent documents for clinical trials to be concise and start with the information most relevant for enrollment decisions. However, there is limited guidance on how to identify this information or evaluate its impact. Design. Participants with a self-reported asthma diagnosis were randomized to one of five versions of the informed consent document for a clinical trial of an injectable asthma product: the original, full-length document; a concise version, removing information identified by asthma patients in an earlier study as not relevant to their enrollment decisions; an interactive version, where participants self-navigated to the information they chose; a reordered version, moving up information deemed more relevant for enrollment in an earlier study; and a highlights version, following the suggested revised Common Rule structure, starting with a summary of enrollment-relevant information based on patient ratings. Knowledge acquisition was evaluated with a knowledge test, with submeasures for information that had high and low relevance for enrollment decisions. Results. Participants who saw the highlights (“Common Rule”) version were more likely to answer questions about high enrollment-relevant information correctly than were participants who saw the full-length version (65% v 59%, P = 0.0105). Participants who saw the other revised versions did not perform significantly differently from the full-length version. Conclusions. An informed consent document designed to implement revised US Federal Common Rule requirements performed better than other designs, in terms of readers retaining information relevant for clinical trial enrollment, as characterized by potential trial participants in a separate study.

Legal and Ethical Issues in Clinical Pharmacy Research — Informed Consent, Part II

1980 ◽  
Vol 14 (2) ◽  
pp. 122-125
Author(s):  
Dev S. Pathak ◽  
Thomas S. Foster ◽  
Cynthia L. Raehl
Keyword(s):  
Informed Consent ◽  
Health Education ◽  
Clinical Pharmacy ◽  
Ethical Issues ◽  
Review Committee ◽  
Department Of Health ◽  
Institutional Review ◽  
Consent Document ◽  
Informed Consent Document ◽  
Legal And Ethical Issues

Preparation of an effective informed consent document presents significant problems to those investigators not familiar with federal and institutional requirements. This article examines a detailed format for preparation of an informed consent instrument. Prepared by the authors and supplied to potential clinical investigators by a university institutional review committee, the guidelines incorporate Department of Health, Education, and Welfare regulations. An example consent form is provided.

Stress, Job Satisfaction, Coping, and Psychological Distress Among Emergency Medical Technicians

1997 ◽  
Vol 12 (4) ◽  
pp. 9-16 ◽  
Author(s):  
Edwin Boudreaux ◽  
Cris Mandry ◽  
Phillip J. Brantley
Keyword(s):  
Job Satisfaction ◽  
Nervous System ◽  
Psychological Distress ◽  
Autonomic Nervous System ◽  
Coping Styles ◽  
Emergency Medical Technicians ◽  
Consent Document ◽  
Informed Consent Document ◽  
Related Stress ◽  
Job Related Stress

AbstractIntroduction:Although several studies link job-related stressors with adverse reactions among emergency medical technicians (EMTs), more standardized research is needed, since much remains unknown about stress responses, coping styles and their consequences for EMTs. This paper presents the results of two studies. Study I investigated the relation between job-related stressors, job satisfaction, and psychological distress, while Study II investigated how coping is related to occupational burnout, job-related stress, and physiological arousal.Hypothesis:Study I: Those EMTs experiencing greater job-related stressors are less satisfied with their jobs and more psychologically distressed.Objective, Study II:To obtain preliminary information about which coping strategies are associated with greater feelings of stress and burnout and more intense autonomic nervous system reactivity.Methods:For both studies, EMTs from a large, urban, public EMS organization in the southern United States were asked to participate. Study I: Subjects completed an informed consent document, a demographics questionnaire, a measure of job stress (the Stress Diagnosis Inventory), a measure of job satisfaction (Job-in-General), and a measure of psychological symptomatology (Symptom Checklist-90, Revised). Pearson product-moment correlations were computed between the measures. Study II: Subjects completed an informed consent document, a demographics/information sheet, the Maslach Burnout Inventory (MBI), and the Ways of Coping Scale (WOCS). They then completed 30 days of monitoring using the Daily Stress Inventory (DSI) and the Daily Autonomic Nervous System Response Inventory (DANSRI). Pearson product-moment correlations were computed between the measures.Results:Study I: Those EMTs who experienced greater job-related stress also were significantly more dissatisfied with their jobs, more depressed, anxious, hostile, and endorsed greater global psychological distress. Study IT. The Depersonalization subscale on the MBI correlated significantly with the following WOCS subscales: Accepting Responsibility, Confrontive Coping, Distancing, and Escape/Avoidance. Emotional Exhaustion on the MBI correlated significantly with Confrontive Coping, Escape/Avoidance, and Social Support, while data obtained on the 40 subjects who completed the daily monitoring revealed that DSI-Impact, DANSRI-Number, and DANSRI-Impact scores each correlated significantly with Accepting Responsibility, Confrontive Coping, and Escape/Avoidance.Conclusion:A significant portion of an EMT's job satisfaction and psychological well-being is associated with the degree to which they are experiencing job-related stress, and, furthermore, this distress level appears to be clinically elevated. This implies that in-service programs and psychological support services designed to help EMTs manage their job-related stress may improve job satisfaction and decrease psychological distress. The coping styles most consistently associated with maladaptive outcomes were: Accepting Responsibility, Confrontive Coping, and Escape/Avoidance. Thus, subjects who were more likely to handle stress with self-blame, aggression, hostility, and risk taking or with wishful thinking, escape tendencies, and avoidance were more likely to endorse more negative outcomes.

scholarly journals Analysis of Information Submitted by Clinical Trial Sponsors regarding the Safety of Investigational Drugs

2004 ◽  
Vol 124 (4) ◽  
pp. 225-229
Author(s):  
Risa TAKAYANAGI ◽  
Yuko NAKAMURA ◽  
Yuko NAKAJIMA ◽  
Akemi SHIMIZU ◽  
Hitoshi NAKAMURA ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Investigational Drugs

scholarly journals 665 Transcriptional landscape of tumor-reactive TIL in lung cancer and melanoma

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A693-A693
Author(s):  
Jiajia Zhang ◽  
Justina Caushi ◽  
Boyang Zhang ◽  
Zhicheng Ji ◽  
Taibo Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trial ◽  
T Cells ◽  
Informed Consent ◽  
T Cell ◽  
Cancer Center ◽  
Lung Cancers ◽  
Functional Assays ◽  
Link Type ◽  
Institutional Review

BackgroundMelanoma and lung cancers have two of the highest response rates to immune checkpoint inhibitors (ICIs).1 However, patients may respond unpredictably, partly due to heterogeneity in the quantity and quality of tumor-specific T cells. In this study, we performed an integrated transcriptomic analysis of anti-tumor CD8+ TIL from non-small cell lung cancer (NSCLC) and melanoma. Our goal was to study the global transcriptomic landscape of tumor-specific T cells and to compare their functional programming in lung cancer vs. melanoma.MethodsTIL from 19 patients (15 NSCLC and 3 melanoma) were sequenced using combined single-cell (sc) RNA-seq/TCR-seq. All NSCLC patients received neoadjuvant anti-PD-1 (nivolumab, NCT02259621) whereas melanoma patients received a personal neoantigen vaccine (NCT01970358). Neoantigen-, tumor-associated antigen-, and viral-specific CD8+ T cell clonotypes were identified using functional assays and were validated by TCR cloning as previously described.2 3 Transcriptional profiles of antigen-specific T cells were identified using the TCRβ CDR3 as a barcode to link with the antigen specificity output from the functional assays. The prevalence, phenotype, and differentiation trajectory of tumor-specific T cells were compared between the two cancer types.ResultsA total of 175,826 CD8+ TIL were analyzed, of which 30,174 single cells were from the melanoma cohort and 145,652 were from the NSCLC cohort. Tumor-specific T cells were detected at variable frequencies among CD8+ TIL (median=1.2%, range 0.01%–35.8%) across nine patients, with melanoma having more clonal tumor-specific T cells as compared to NSCLC. CD8+ TIL from melanoma were more enriched in an activated tissue resident T cell (TRM) cluster characterized by upregulated expression of CXCL13, CRTAM, 4-1BB, XCL1/2, and FABP5, whereas those from NSCLC have a greater representation of a cytotoxic TRM cluster with an exhaustion signature (coexpression of GZMB, GZMH, PDCD1, and CTLA4). Distinct from EBV-specific T cells and flu-specific T cells, tumor-specific T cells primarily resided in TRM clusters in both cancers. More MANA-specific TIL from melanoma presented with an effector phenotype and were more proliferative as compared to those from NSCLC. To reveal the differentiation trajectory and regulatory programs of tumor-specific T cells upon tumor recognition and association with response to ICIs, pseudotime/velocity analysis of tumor-specific TIL is underway.ConclusionsThis is the first analysis to inform on the global transcriptomic landscape of tumor-specific CD8+ TIL in lung cancer and melanoma at single cell resolution. This provides a useful framework to study the underlying mechanisms of T cell exhaustion and dysfunction in human cancer.Trial RegistrationNCT02259621,NCT01970358ReferencesYarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to PD-1 inhibition. The New England Journal of Medicine 2017;377(25):2500.Caushi JX, et al. Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature 2021;1–7.Oliveira G, et al. Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma. Nature 2021;1–7.Ethics ApprovalThe melanoma clinical trial was approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (IRB) (NCT01970358). The NSCLC clinical trial was approved by the Institutional Review Boards (IRB) at Johns Hopkins University (JHU) and Memorial Sloan Kettering Cancer Center (NCT02259621). All participants gave informed consent before taking part.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Ex Vivo Expansion of Genetically Marked Rhesus Peripheral Blood Progenitor Cells Results in Diminished Long-Term Repopulating Ability

Blood ◽  
1998 ◽  
Vol 92 (4) ◽  
pp. 1131-1141 ◽  
Author(s):  
J.F. Tisdale ◽  
Y. Hanazono ◽  
S.E. Sellers ◽  
B.A. Agricola ◽  
M.E. Metzger ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Ex Vivo ◽  
Retroviral Vectors ◽  
Ex Vivo Expansion ◽  
Us Government ◽  
Government Work ◽  
Stromal Support ◽  
Short And Long Term

Abstract The possibility of primitive hematopoietic cell ex vivo expansion is of interest for both gene therapy and transplantation applications. The engraftment of autologous rhesus peripheral blood (PB) progenitors expanded 10 to 14 days were tracked in vivo using genetic marking. Stem cell factor (SCF)/granulocyte colony-stimulating factor (G-CSF)–mobilized and CD34-enriched PB cells were divided into two equal aliquots and transduced with one of two retroviral vectors carrying the neomycin-resistance gene (neo) for 4 days in the presence of interleukin-3 (IL-3), IL-6, and SCF in the first 5 animals, IL-3/IL-6/SCF/Flt-3 ligand (FLT) in 2 subsequent animals, or IL-3/IL-6/SCF/FLT plus an autologous stromal monolayer (STR) in the final 2. At the end of transduction period, one aliquot (nonexpanded) from each animal was frozen, whereas the other was expanded under the same conditions but without vector for a total of 14 days before freezing. After total body irradiation, both the nonexpanded and expanded transduced cells were reinfused. Despite 5- to 13-fold higher cell and colony-forming unit (CFU) doses from the expanded fraction of marked cells, there was greater short- and long-term marking from the nonexpanded cells in all animals. In animals receiving cells transduced and expanded in the presence of IL-3/IL-6/SCF/FLT, engraftment by the marked expanded cells was further diminished. This discrepancy was even more pronounced in the animals who received cells transduced and expanded in the presence of FLT and autologous stroma, with no marking detectable from the expanded cells. Despite lack of evidence for expansion of engrafting cells, we found that the addition of FLT and especially STR during the initial brief transduction period increased engraftment with marked cells into a clinically relevant range. Levels of marked progeny cells originating from the nonexpanded aliqouts were significantly higher than that seen in previous 4 animals receiving cells transduced in the presence of IL-3/IL-6/SCF, with levels of 10% to 20% confirmed by Southern blotting from the nonexpanded IL-3/IL-6/SCF/FLT/STR graft compared with 0.01% in the original IL-3/IL-6/SCF cohort. These results suggest that, although expansion of PB progenitors is feasible ex vivo, their contribution towards both short- and long-term engraftment is markedly impaired. However, a brief transduction in the presence of specific cytokines and stromal support allows engraftment with an encouraging number of retrovirally modified cells. This is a US government work. There are no restrictions on its use.

scholarly journals INFORMED CONSENT IN CLINICAL TRIALS FOR PERSONS WITH DEMENTIA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S28-S28 ◽  
Author(s):  
Joan G Carpenter
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Informed Consent ◽  
Nursing Homes ◽  
Decision Maker ◽  
Surrogate Decision Maker ◽  
Decision Making Capacity ◽  
Consent Document ◽  
Surrogate Decision

Abstract Informed consent is one of the most important processes during the implementation of a clinical trial; special attention must be given to meeting the needs of persons with dementia in nursing homes who have impaired decision making capacity. We overcame several challenges during enrollment and consent of potential participants in a pilot clinical trial including: (1) the consent document was designed for legally authorized representatives however some potential participants were capable of making their own decisions; (2) the written document was lengthy yet all seven pages were required by the IRB; (3) the required legal wording was difficult to understand and deterred potential participants; and (4) the primary mode of communication was via phone. We tailored assent and informed consent procedures to persons with dementia and their legally authorized representative/surrogate decision maker to avoid risking an incomplete trial and to improve generalizability of trial results to all persons with dementia.

Informed Consent Document and Process in India: Ethical and Quality Issues

2016 ◽  
Vol 8 (1) ◽  
pp. 37-52
Author(s):  
Madhuri Patel ◽  
Kannan Sridharan ◽  
Jayesh Patel
Keyword(s):  
Informed Consent ◽  
Consent Document ◽  
Informed Consent Document ◽  
Quality Issues
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