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ABSTRACT To develop a more efficient way of informing potential clinical trial volunteers of exactly what they could expect during (and after) their participation in a clinical trial as well as the sponsor’s expectations from the volunteer. A multiple choice questionnaire, which was based on the criteria as specified by Guideline 5 of the International Conference of Harmonization (ICH), was administered to 28 Volunteers after only reading the Patient Information Leaflet/Informed Consent Document (PIL/PIL/ICD), to 21 Volunteers who had read the PIL/ICD and attended a question and answer session, to 17 Volunteers who had read the PIL/ICD and attended a presentation and 19 Volunteers who had read the PIL/ICD and attended a presentation and a question and answer session. In total, 85 Volunteers completed the questionnaire. The average calculated percentage* of volunteers who had only read the PIL/ICD was 61%, 63% for Volunteers who had read the PIL/ICD and attended a question and answer session, 73% for Volunteers who had read the PIL/ICD and attended a presentation and 68% for Volunteers who had read the PIL/ICD and attended a presentation and question and answer session. In total, the average calculated percentage was 66%. Eighty four percent of the total number of volunteers answered the question on withdrawal consequence incorrectly, 43% of Volunteers answered questions on side effects incorrectly and 100% of the Volunteers answered the question on the duration of storage of samples incorrectly. Despite increasing regulatory and ethical scrutiny, deficiencies still exist in Volunteer comprehension of the research in which they participate, as well as differences in how comprehension is measured and assessed. Results indicated that any successful consent process should, at a minimum, include a visual communication mode. Concepts that are not well understood within the South-African context are withdrawal consequence, methodology such as double-blind or single blind, side effects, duration of archiving, treatment alternatives and the role of the investigator. *calculated % for each volunteer = score out of 25 x 100

MSc (Med), Pharmaceutical Affairs, Faculty of Health Sciences, University of the Witwatersrand / Quality Assurance (QA) Audits are an essential component and an integral part of clinical trials. As a quality improvement tool, forming part of Good Clinical Practice (GCP) an audit can demonstrate that real efforts are being made to improve and enhance the quality of professional care to all trial subjects participating in clinical trials. Specifically, clinical research performed on the central nervous system (CNS) involves distinctive areas of concern to adherence to good clinical practice in this therapeutic area. For example an informed consent process not conducted appropriately for subjects with e.g. Schizophrenia or Alzheimer’s disease; or inter-individual rating differences in instances when different investigators (psychiatrist) assess a trial subject. A need was identified to analyze the association between the CNS indication audited and the audit findings and to perform a trend analysis that highlight re-occuring audit findings. A total of 123 CNS audit reports were obtained from the Quality Assurance Departments of Quintiles in South Africa and Europe. The audit reports were grouped into the 15 CNS indications that were audited. Five hundred and six (506) audit findings were derived from the 123 CNS audits reports. The audit findings were categorized according to GCP subject matter, regulatory requirements or Standard Operating Procedures (SOPs). The severity of audit findings was classified as critical or major. The results of this investigation suggested a need for substantial improvement in three important areas. Firstly; adherence to the study requirements inclusive of relevant Standard Operating Procedures (SOPs). Secondly the development of better defined protocols and thirdly training of monitors. Study planners and Clinical Trial Management should take a proactive role to minimize the audit findings by ensuring monitors with experience in the research field should be involved in the study. Procedures should be implemented to educate site staff. Focus should be placed on the importance of detailed source documentation, adherence to investigational product dosage requirements, the conduct of the informed consent process, and adequate study documentation maintenance.

Objective: To compare and contrast doravirine (DOR) with other agents in the nonnucleoside reverse transcriptase inhibitor (NNRTI) class, review safety and efficacy data from both completed and ongoing clinical trials, and outline the potential place in therapy of DOR. Data Sources: A literature search using the PubMed database (inception to June 2019) was conducted using the search terms HIV, doravirine, non-nucleoside reverse transcriptase inhibitor, NNRTI, and MK-1439. Study Selection and Data Extraction: Clinical data were limited to those published in the English language from phase 2 or 3 clinical trials. Ongoing trials were identified through ClinicalTrials.gov. Data Synthesis: DOR was approved by the US Food and Drug Administration on the strength of 2 phase 3 randomized, double-blind, noninferiority clinical trials with additional studies currently underway examining its utility in other clinical scenarios. Relevance to Patient Care and Clinical Practice: The role of NNRTIs as part of antiretroviral (ARV) therapy has diminished in recent years given the introduction of more tolerable individual ARV agents and regimens. Despite this, new agents are still needed in the therapeutic arena because treatment failure as well as intolerance can still occur with many first-line therapies. The optimal place in therapy of DOR remains to be defined. Conclusions: DOR is a new NNRTI that represents a potential treatment option for treatment-naïve patients, without many of the previously described untoward effects of the NNRTI class.

Clinical drug trials are costly and time-consuming. Bayesian methods alleviate the inefficiencies in the testing process while providing user-friendly probabilistic inference and predictions from the sampled posterior distributions, saving resources, time, and money. We propose a dynamic linear model to estimate the mean response at each dose level, borrowing strength across dose levels. Our model permits nonmonotonicity of the dose-response relationship, facilitating precise modeling of a wider array of dose-response relationships (including the possibility of toxicity). In addition, we incorporate an adaptive approach to the design of the clinical trial, which allows for interim decisions and assignment to doses based on dose-response uncertainty and dose efficacy. The interim decisions we consider are stopping early for success and stopping early for futility, allowing for patient and time savings in the drug development process. These methods complement current clinical trial design research.

FDA decisions and late-stage clinical trial results regarding new pharmaceutical approvals can cause extreme moves in the share price of small biopharmaceutical companies. Throughout the clinical trial process, many potential investors are exposed to market-moving information before such information is made available to the investing public. An investor who wished to profit from advance knowledge about clinical trial results may use the publicly traded options markets in order to increase leverage and maximize profits. This research examined options data surrounding the public release of information pertaining to the efficacy of clinical trials and approval decisions made by the FDA. Events were identified for small pharmaceutical companies with fewer than three currently approved drugs in an attempt to isolate the effect of individual clinical trial and FDA-related events on the share price of the underlying company. Option data were analyzed using logistic regression models in an attempt to predict phase II and III clinical trial outcome results and FDA new drug approval decisions. Implied volatility, open interest, and option contract delta values were the primary independent variables used to predict positive or negative event outcomes. The dichotomized version of a predictor variable designed to estimate total investment exposure incorporating open interest, option contract delta values, and the underlying stock price was a significant predictor of negative pharmaceutical related events. However, none of ii the variables examined in this research were significant predictors of positive drug research related events. The estimated total investment exposure variable used in this research can be applied to the prediction of future clinical trial and FDA decision related events when this predictor variable shows a negative signal. Additional research would help confirm this finding by increasing the sample size of events that potentially follow the same pattern as those examined in this research. / text