ABSTRACT
Incorporating patient perspectives into clinical studies is recognized as important to the development of high-quality, safe, and effective fit-for-patient medicines. However, no widely accepted methodology to help design more patient-centered studies has been established systematically. TransCelerate Biopharma Inc., a non-profit organization promoting collaboration across biopharmaceutical companies, organized a Patient Experience (PE) Initiative to create tools to intentionally include the patient perspective into the design and implementation of clinical studies. The resulting tools include the Patient Protocol Engagement Toolkit (P-PET), to engage patients early in protocol development, and the Study Participant Feedback Questionnaire (SPFQ), to assess patient experiences during clinical studies. To develop these toolkits, TransCelerate conducted a literature review and identified aspects of clinical studies that patients find either valuable or burdensome, or that affect participation, adherence, and engagement in a clinical study. The concepts identified were refined through elicitation of feedback from patient advisors, clinical study site advisors, and subject matter experts from member companies (MCs) of TransCelerate. This feedback was considered in identifying gaps, defining scientific methodology to understand how to evaluate patients' needs, and developing and refining the P-PET and the SPFQ. As part of the development process, descriptions/drafts of the tools were shared with patients, clinical site advisory groups, MCs, and the US Food and Drug Administration, and then revised. MCs simulated use of the tools, and feedback was incorporated into the final versions of the P-PET and SPFQ prior to public release. The P-PET and SPFQ are available free on the TransCelerate website.
Subject(s)
Patient Participation , Humans , Patient-Centered Care , Research Design , Surveys and Questionnaires , United States , United States Food and Drug AdministrationABSTRACT
When actively sensitised rats were injected intraperitoneally with antigen, the local reaction that ensued can be divided into two phases: an immediate reaction characterised by histamine and SRS-A release with an associated extravasation of plasma proteins, and a later reaction involving infiltration of neutrophilic polymorphonuclear leucocytes. When the immediate reaction was modified by BRL 10833 (which inhibits histamine release from rat mast cells and reduces extravasation of plasma proteins), there was no reduction in neutrophil infiltration. FPL 55712, an SRS-A antagonist, also failed to inhibit neutrophil infiltration. The beta-adrenoreceptor stimulants isoprenaline and salbutamol reduced neutrophil infiltration. Isoprenaline inhibited the extravasation of plasma proteins when given before antigen, but even when administered to rats after antigen, when extravasation was complete, it still inhibited neutrophil infiltration. Propranolol reversed isoprenaline-induced inhibition of neutrophil infiltration.
Subject(s)
Adrenergic beta-Agonists/pharmacology , Chromones/pharmacology , Hypersensitivity/immunology , Indans/pharmacology , Indenes/pharmacology , Inflammation/immunology , Propranolol/pharmacology , Animals , Antigens , Blood Proteins/metabolism , Ethers/pharmacology , Histamine Release/drug effects , Immunization , Male , Neutrophils/immunology , Rats , SRS-A/metabolismABSTRACT
Rats actively sensitised to bovine serum albumin (BSA) in Freund's complete adjuvant were challenged by intraperitoneal injection of BSA. By washing out the peritoneal cavities at different times it was possible to divide the changes that occurred into two phases. The first was characterised by the release of histamine and slow reacting substance of anaphylaxis (SRS-A) with an associated extravasation of plasma proteins. The second phase was characterised by an increase in neutrophilic polymorphonuclear cells in the peritoneal cavity. Extracellular enzyme activites were also investigated. The kinetics of these events were studied and are discussed in terms of the possible mechanisms involved.
Subject(s)
Antigens , Immunization , Inflammation/immunology , Animals , Ascitic Fluid/cytology , Ascitic Fluid/metabolism , Blood Proteins/metabolism , Histamine Release , Kinetics , Leukocytes , Male , Rats , SRS-A/metabolism , Serum Albumin, Bovine/immunologyABSTRACT
A nitroindanedione (BRL 10833) inhibited the antigen induced release of histamine and slow reacting substance of anaphylaxis (SRS-A) from passively sensitized human lung at similar concentrations to those required for the inhibition of histamine release by disodium cromoglycate (DSCG). BRL 10833 was more potent than DSCG as an inhibitor of histamine release by antigen from actively and passively sensitized rat peritoneal cells and rat skin fragments.
Subject(s)
Histamine Release/drug effects , Indans/therapeutic use , Indenes/therapeutic use , Passive Cutaneous Anaphylaxis/drug effects , SRS-A/metabolism , Animals , Antigens , Cells, Cultured , Cromolyn Sodium/pharmacology , Humans , Leukocytes/metabolism , Lung/metabolism , Male , Rats , Skin/drug effectsABSTRACT
Passive peritoneal anaphylaxis in rats, sensitized with mouse antiserum, had characteristics of an IgE-mediated reaction, in that the serum was heat-labile and pretreatment of the rats with disodium cromoglycate (DSCG), or sodium nivimedone, inhibited the release of both histamine and slow-reacting substance of anaphylaxis (SRS-A). Sodium nivimedone was more potent than DSCG as an inhibitor of histamine release. Peak concentrations of histamine and SRS-A in the peritoneal fluids of the rats, were reached within 2 min of antigen challenge and fell to control levels after 20-30 min.
