14 results
506 Examining Participant Representation in Atopic Dermatitis Clinical Trials from 2011-2022
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- Eunjoo Pacifici, Kaye Karen Manrique, Araksi L Terteryan, Emily Lai
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 150
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OBJECTIVES/GOALS: This study seeks to comprehensively evaluate the extent to which participants in clinical trials (CT) for Atopic Dermatitis (AD) accurately mirror the demographics and characteristics of the broader AD-affected populations. We will achieve this objective by analyzing data from AD CTs spanning the years 2011 to 2022. METHODS/STUDY POPULATION: We examined completed trials for 10 FDA approved treatments for AD, utilizing data sourced fromclinicaltrials.gov [http://clinicaltrials.gov]. In light of the increased number of AD clinical trials over the past decade, we tailored our search parameters to encampass all trials related to approved treatments from 2011-2022. To assess the characteristics of the participant population in these trials, information including inclusion and exclusion criteria, age, location, sex, and disease severity were collected for each trial. Furthermore, race and ethnicity data were also extracted and analyzed. Additionally, comparisons were drawn between trials completed before and after April 2017, when the FDA began requiring that researchers publish race and ethnicity data toclinicaltrials.gov [http://clinicaltrials.gov]. RESULTS/ANTICIPATED RESULTS: Across 67 CTs examined, 45% of trials were restricted to adult patients, 28% were restricted to pediatric patients, and 27% included both. 77% of CTs occurred in urban settings and 23% occurred in rural settings according to the The Economic Research Service definition. 36% of CTs included mild-to-moderate AD patients, and 64% of CTs included moderate-to-severe AD patients. Race distribution of CTs revealed 67% White, 14% Black/African American, 16% Asian, and 3% others. 13% of participants identified as Hispanic or Latino. With further analysis, we will determine whether there is a difference in ethnic distribution between trials completed before and after April 2017, when the FDA started requiring race/ethnicity data to be submitted. DISCUSSION/SIGNIFICANCE: The findings highlight a significant concern in AD CTs: the insufficient representation of Black and Asian populations. The findings emphasize the need for a more inclusive selection process that accurately reflects the diversity of patients. Failing to do so could undermine the assessment of treatment effectiveness in such populations.
510 Addressing the Regulatory Needs and Challenges of Academic Researchers by Creating a One-Stop Shop Web Portal
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- Karen Manrique, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 151
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OBJECTIVES/GOALS: To identify challenges faced by academic researchers in accessing online regulatory information and/or tools to advance their research work to develop a free, publicly accessible, interactive web portal that provides regulatory support. METHODS/STUDY POPULATION: The Regulatory Knowledge and Support core of the Southern California Clinical and Translational Science Institute interviewed five local research professionals. These interviews guided the development of a Qualtrics survey, consisting of multiple responses and open-ended questions, submitted to our local institutional review board (IRB). After receiving IRB approval, the survey was disseminated via email, newsletters, flyers, and presentations targeting researchers at academic institutions and members of clinical and translational science hubs. Survey data will be used to identify the challenges academic researchers face in finding regulatory resources and to compile the types of regulatory information or tools they would find helpful for their research. RESULTS/ANTICIPATED RESULTS: According to the interviews, researchers with extensive involvement in clinical trials found regulatory resources easily accessible compared to those with less experience. Additionally, they all stated having a colleague or regulatory specialist whom they can consult about regulatory requirements. Insights from these initial interviews confirmed the need to obtain a comprehensive view across research professionals. Anticipated results will show the challenges in accessibility, source, and type of regulatory resources researchers typically encounter. It is also anticipated that researchers will share what kinds of resources they would find most useful for their work. Ultimately, the information and tools identified as essential by survey takers will be collected and incorporated into the web portal. DISCUSSION/SIGNIFICANCE: Academic researchers find navigating through regulatory hurdles persistently challenging when translating their work from bench to clinic, especially since academia is typically resource-constrained. Findings from this study will allow the creation of a web portal for researchers that is broadly accessible and meets their regulatory needs.
220 The Unheard Voices of Clinical Trials: Fostering Inclusivity for People Experiencing Homelessness in Clinical Trials
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- Bruno Baltazar, Sherman Wu, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 67
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OBJECTIVES/GOALS: Investigate the perspectives of people experiencing homelessness (PEH) on clinical trials to uncover knowledge gaps and attitudes. This study aims to offer insights for clinical researchers to enhance engagement with this marginalized group, ushering in a more inclusive clinical trial process. METHODS/STUDY POPULATION: A 14-question survey was developed in collaboration with the Street Medicine Team at the University of Southern California and other stakeholders of PEH research. Initial questions assess knowledge of clinical trials, followed by questions gauging sentiments on clinical trial participation, and final questions on the significance, benefits, and risks of clinical trials. Upon approval by the local Institutional Review Board, the survey will be administered in an interview format. Study participants will be from locations within the area of operations of the USC Street Medicine team–in and around Hollywood, South Los Angeles, and/or the Los Angeles Council District 1. RESULTS/ANTICIPATED RESULTS: We anticipate that the results of this study will offer valuable insights into the perspectives of PEH regarding clinical trials. Results will also provide varying levels of knowledge and understanding among PEH about clinical trials, along with their past experiences in clinical trial participation, and willingness for future involvement in such trials. Further, the results will reveal whether respondents feel they are being properly represented in clinical research projects that could impact themselves and their community. This project can also enhance our understanding of the expectations and concerns of PEH regarding their potential participation in clinical trials. DISCUSSION/SIGNIFICANCE: The outcomes of this research project have the potential to lay the groundwork for enhancing the involvement of PEH in translational science research, encompassing aspects from study design to participation. This improvement could benefit not only participants but also various stakeholders involved.
391 An Investigation on the Activity of Repurposing Already Marketed Drugs for New Indications from 2015 to 2021.
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- Wenchao Wu, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 116
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OBJECTIVES/GOALS: To examine the prevalence of new indications for existing drugs conducted by non-originator companies from 2015 to 2021 and determine how many could qualify for 505(b)(2) under the Food, Drug, and Cosmetics Act. METHODS/STUDY POPULATION: A search within Clinicaltrials.gov was conducted to identify phase 3 drug interventional studies completed from 2015 to 2021. Results were categorized by funding source and industry sponsored studies were further separated into originator- and non-originator companies using dailymed.com. An in-depth review of 2018 was conducted to understand the nature of the studies including indication, dosage form, and route of administration. RESULTS/ANTICIPATED RESULTS: According to clinicaltrials.gov, a total of 7148 phase 3 studies were conducted between 2015 and 2021. Most of these studies were funded by industry (4447, 66.21%), followed by other (2428, 33.97%), NIH (266, 3.72%), and government (62, 0.87%). In-depth examination of the studies completed in 2018 (n=1077) revealed similar pattern in that most were funded by industry (674, 62.58%) followed by other (356, 33.05%), NIH (43, 3.99%), and government (10, 0.93%). Some studies were funded by more than one type. Of the industry-sponsored studies, 623 were funded by originator companies and 51 by non-originator companies. A total of 49/674 of the industry sponsored studies were for new indications, with 42 studies conducted by originator companies and 7 conducted by non-originator companies. DISCUSSION/SIGNIFICANCE: The 505(b)(2) is a way for manufacturers to add new indications to drugs by non-originator companies. In 2018, 49/674 studies were conducted to pursue new indications with few, 7/49, conducted by non-originator companies. The product development landscape reveals few opportunities for entities pursuing the 505(b)(2) pathway for new indications.
394 Examining the Landscape of Clinical Trials Targeting Alcohol or Opioid Use Among Homeless Individuals
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- Bruno Baltazar, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 7 / Issue s1 / April 2023
- Published online by Cambridge University Press:
- 24 April 2023, p. 117
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OBJECTIVES/GOALS: To understand the current landscape of clinical trials involving the homeless population by examining opioid or alcohol use disorders and the challenges in clinical trial recruitment. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched with the keywords homeless or unhoused. The search was limited to studies conducted in the United States that were recruiting, not yet recruiting, active and not recruiting, completed, and enrolling. The search findings were further characterized and categorized by the definitions that were used for homelessness. Next, the trials were grouped based on the inclusion of alcohol or opioid use: (A) had no relevant mention, (B) included alcohol or opioid use as a secondary or other outcome measure, or (C) alcohol or opioid were the primary focus of the trial. Lastly, patterns and trends were identified for these trials. RESULTS/ANTICIPATED RESULTS: Out of 161 trials, 77 trials that met search criteria were identified then grouped based on how they classified homelessness: McKinney-Vento (n=5, 6%), DHHS (n=4, 5%), HUD (n=2, 3%), HEARTH Act (n=3, 4%), Custom (trials that specified parameters for homelessness, n=12, 16%), Not Specified (trials that provided no parameters for homelessness, n=26, 34%), and Other/Ambiguous (trials that used enrollment in an independent program as parameters or had unclear parameters, n=25, 32%). Of the 77 clinical trials that targeted homeless populations, 65% did not include alcohol use and 100% did not include opioid use in any outcome measure, 22% included alcohol use in a non-primary outcome measure, and 13% included alcohol use as the primary outcome measure of the study. DISCUSSION/SIGNIFICANCE: The number of clinical trials targeting homeless populations has increased over time, yet there is still no universal definition for classifying an individual as homeless. This lack of harmonization poses a challenge when coupled with the findings that there is a lack of clinical trials targeting opioid or alcohol use disorders.
377 Mapping Clinical Trial Outcome Measures for Atopic Dermatitis
- Nicholas Naumov, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 6 / Issue s1 / April 2022
- Published online by Cambridge University Press:
- 19 April 2022, p. 71
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OBJECTIVES/GOALS: Atopic Dermatitis (AD) affects 10% of people globally and is studied widely in clinical trials. However, clinical outcomes assessment (COA) for AD are not standardized, hindering easy comparisons across different studies. This study examines AD studies to identify the most used COAs. METHODS/STUDY POPULATION: Clinicaltrials.gov was searched to identify AD trials conducted between 2011 and 2021. Ongoing and completed trials were classified according to the therapeutic modality: Biologic, Immunosuppressive, or Other (botanicals and antibiotics). Further, AD trials were examined to determine which of the COAs listed in the FDA compendium issued in 2021 were included: the Investigators Global Assessment (IGA), the Eczema Area and Severity Index (EASI-75), and the Pruritus Numeric Rating Scale (NRS). The results were analyzed to determine which COA is most frequently used and if there were differences across therapeutic modalities or trial phases. RESULTS/ANTICIPATED RESULTS: Across a total of 50 AD trials registered in clinicaltrials.gov, EASI-75 was the most used COA; the item was included in 12 of 16 biologics, 5 of 14 immunosuppressives, and 7 of 20 other products. Moreover, AD trials of biologics included more of the FDA-suggested COAs than those studying other modalities. There were also differences across the clinical trial phases in that most phase III AD trials (83.33%, n=8) included two of the three COAs listed (IGA and EASI-75) compared to less than half of phase I/II trials (vs. 43.75%, n=32). DISCUSSION/SIGNIFICANCE: Findings from this study indicate a lack of COA harmonization across AD trials, impeding comparative analysis of the trial results. Establishing a common standard for COA would foster communication and transparency among key stakeholders including researchers, healthcare providers, and patients.
4349 Survey of Regulatory Reforms to Address Comprehension of Clinical Trial Results
- Matthieu Kirkland, Christian Reyes, Nancy Pire-Smerkanich, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 115
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OBJECTIVES/GOALS: Clinical research is the backbone of the medical community. However, there are few regulations to ensure clinical trial participants can understand their results, leading to volunteers feeling unvalued and unlikely to enroll in trials1. This study examines the need of lay summaries METHODS/STUDY POPULATION: To understand the current landscape of clinical trial summaries, literature searches were conducted using the University of Southern California Library database with keywords Title contains “lay language” OR “lay summary” AND any field contains “Trial” OR “clinical”, and Title contains “natural language processing” AND “clinical trial” OR “Summary”. Studies were deemed relevant if they discussed lay language summaries for health care realms or using Natural Language Processing (NLP) to increase comprehension. Papers published by the Center for Information and Study on Clinical Research Participation (CISCRP) were reviewed and their Associate Director was interviewed. RESULTS/ANTICIPATED RESULTS: Of 67 total results, 14 were determined to be relevant. Ten of the relevant results examined lay language summaries and their regulation and 4 were NLP studies. The European Medicines Agency set regulations mandating clinical trial summaries. However, researchers have difficulty validating to an appropriate reading level2. Difficulty and potential bias halted a U.S. mandate of lay summaries3. The nonprofit CISCRP has partnered with industry to develop unbiased clinical trial summaries resulting in all volunteers feeling appreciated and 91% understanding clinical trial results post summary1. Similarly, NLP software for annotating Electronic Health Records increased comprehension for 77% of patients4. DISCUSSION/SIGNIFICANCE OF IMPACT: In the U.S., a lack of regulations mandating lay summaries may be related to concerns by regulatory agencies that summaries in plain language may introduce bias3. Future looks into integration of NLP systems to clinical trials may create unbiased summaries and allow for FDA regulation.
4505 Implementation of Real-World Data and Real-World Evidence in Clinical Studies
- Jessica Pham, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 114
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OBJECTIVES/GOALS: Real-world studies have been gaining momentum in providing evidence of treatment effectiveness and hold great potential for facilitating the drug regulatory process. The U.S. Food and Drug Administration (FDA) has recognized this by providing a framework for using real-world data (RWD) to generate real-world evidence (RWE). The objective of this study is to assess the current level of RWE implementation in clinical studies. METHODS/STUDY POPULATION: Using keywords relevant to RWE, we reviewed studies on drugs, biologics, and medical devices published on PubMed in 2018. Information regarding the therapeutic area of focus, intervention type, study design, primary outcome, and data source was recorded. Further analyses of the three main therapeutic areas of study (oncology, cardiology, and infectious diseases) were performed to determine how RWE was being utilized. In addition, a broad “real-world” search was performed on Clinicaltrials.gov, from which we extracted relevant observational and Phase I, II, II/III, III, III/IV, and IV studies. A supplemental PubMed search was used to evaluate published studies in order to identify which field these trials were concentrated in and the outcome of interest.” RESULTS/ANTICIPATED RESULTS: After application of “real-world” search terms to PubMed, 995 hits were generated and of these, 311 studies were excluded. More than half of the studies were observational and retrospective in nature (64%) with 70% examining drug/biologic outcomes. RWE data sources were largely dominated by medical records and claims data. The primary uses of RWE across oncology, cardiology, and infectious diseases included supporting drug product effectiveness, assessing safety, and evaluating treatment patterns. Of the 207 RWE studies identified on ClinicalTrials.gov, 66 were cancer randomized controlled trials (RCTs), a majority of which were used for post-marketing safety evaluations. Further research will be conducted to determine the precise role of RWE in all studies (e.g. historical comparator, label expansion). DISCUSSION/SIGNIFICANCE OF IMPACT: By examining the use of RWE in regulatory decision making, we can inform stakeholders of the extent to which robust RWE studies complement evidence generated by RCTs. Thought to reflect a product’s performance in a broader and more diverse population, RWE can provide greater insight to clinical trial conduct and ultimately transform patient outcomes.
4500 Providing a System for Practical Monitoring Training for Clinical Trials within Academic Institutions
- Advaita Chandramohan, Sukhmani Kaur, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 114-115
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OBJECTIVES/GOALS: The goal was to understand the effectiveness of a novel clinical trial educational module and a corresponding initiative designed and disseminated by the Southern California Clinical and Translational Science Institute (SC-CTSI) to increase the quality of clinical trials conducted in academia. METHODS/STUDY POPULATION: The CRCs (Clinical Research Coordinators) for the initiative are asked to complete the online training. Possible study protocols are picked to be monitored by the CRCs. The monitor is instructed to study the protocol extensively and prepare for their monitoring visit. The trained monitor from the initiative then reaches out to the CRC of the study that is to be monitored and carries out the monitoring visit. Afterwards, the monitor sends initiative personnel the monitoring report, which is evaluated to see if the monitor checked everything they should have during the visit. The PI of the study is contacted with highlights from the monitoring report and improvements that they can make. RESULTS/ANTICIPATED RESULTS: The first study monitored was a site of a large NIH-sponsored study where the consent forms were signed electronically. It was found that the monitor could not access the consent forms. Therefore, the monitor could not do source data verification. The PI of the study said that they would be raising this issue with the NIH. During the monitoring visit of the second study chosen for the initiative, patient binders were specifically examined for informed consent and source documentation completeness. The charts of patients were also reviewed. The only deviation found was a missing signature in the Investigator Site File. For the last two studies, data will be reported. DISCUSSION/SIGNIFICANCE OF IMPACT: Monitors were not only able to monitor efficiently, but also able to point out deficiencies in the monitoring practices of large studies. This model could be expanded to other academic institutions to establish quality management systems to ensure data integrity and subject protection.
4230 An App a Day: Examining Clinical Evidence for Safety and Efficacy of Diabetes Mobile Health Apps
- Avantika Pathak, Susan Bain, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 53-54
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OBJECTIVES/GOALS: Mobile health applications are widely used by the public but vary in how they are classified and regulated. This study examines the evidence of the safety and efficacy of mobile medical applications specifically focusing on those that are used to manage diabetes. METHODS/STUDY POPULATION: To understand the current regulatory landscape of mobile health applications (mHealth apps) for diabetes, a literature survey was conducted using the Pubmed database. Top mHealth apps were identified by searching the Apple store website using 10 key terms associated with diabetes management applications. A maximum of ten results, when available for each key term, were studied by exploring the FDA databases to understand how the products were regulated and if any were subject to recalls. These selected mHealth apps were also searched on clinicaltrials.gov to see if there were ongoing or completed clinical trials and if the trials were designed to include efficacy and safety outcome measures. RESULTS/ANTICIPATED RESULTS: Of the 71 mHealth apps for diabetes management that were identified, 16 were regulated. These products spanned a diverse range of functions including device data and decision support systems. Although 11 had clinical trial data demonstrating efficacy, only 4 had data demonstrating both efficacy and safety. Two of the regulated applications were subject to product recalls due to programming errors that resulted in incorrect insulin dose recommendations. These two applications had clinical trials evaluating efficacy but not safety. The companies noted that the incorrect insulin calculation from their respective mHealth app could cause either a low- or high-impact hypoglycemic event. DISCUSSION/SIGNIFICANCE OF IMPACT: With little to no clinical trial data to support their safety and efficacy, mHealth apps in the diabetes marketplace pose risks for patients as evidenced by recent safety-related recalls. The results of this study indicate that these products may need to be more tightly regulated.
4339 Exploring Physician Investigator Clinical Trials Training and Quality Management Systems and its Implementation in Medical School Curriculums
- Sukhmani Kaur, Advaita Chandramohan, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, p. 31
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OBJECTIVES/GOALS: Although many physicians conduct clinical trials as Principle Investigators, a systematic training is often lacking. Instead, most receive on-site training, potentially compromising data quality and human subject safety. This research assesses the landscape for physician training through medical school curriculums. METHODS/STUDY POPULATION: This project explored training programs for physician researchers, specifically in the emerging field of quality management systems (QMS). To understand the scope of academic research available for QMS and Good Clinical Practice (GCP) training and lack of clinical trial training implemented in medical school curricula, a literature review was conducted. Available training for physicians was assessed through existing training programs from the FDA, NIH, DIAMOND, ACRP, and Google for accessibility in terms of costs, completion timelines and certification, format (online vs. in-person), and inclusion of GCP and QMS training in the curriculum RESULTS/ANTICIPATED RESULTS: Literature review revealed that not much is known about physician researcher training beyond the institutional requirement for minimal GCP review. Examination of select medical school curriculum also discovered a lack of clinical trial training for students interested in clinical research. Furthermore, existing training programs and modules available for physicians are limited as their syllabi do not include QMS training. In addition, these programs commonly have inaccessible registration links, are expensive, and have significant time commitments for in-person courses. These findings support the need for more accessible and effective training and certification tools for physician researchers. DISCUSSION/SIGNIFICANCE OF IMPACT : QMS training is not included medical school curricula or programs for physician researchers, potentially compromising data integrity and subject protection. This research supports the development of essential QMS training concepts and practical approaches for physician researcher clinical trials.
3570 The Regulatory Landscape of Products to Treat Opioid Overdose
- Pooja Singh, Kaylene Okada, Amelia Spinrad, Nancy Pire-Smerkanich, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 58-59
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OBJECTIVES/SPECIFIC AIMS: Since 1971, Naloxone has been the only FDA approved opioid antagonist indicated for use after opioid overdose. New formulations of Naloxone have been introduced into the market, including an injectable, auto-injector, and nasal spray. However, Naloxone is short-acting and as such often requires multiple doses and may induce severe withdrawal symptoms. This study examines the regulatory framework to understand the evolution of products indicated to treat opioid overdose and the landscape of therapies in development. Furthermore, this study examines how the Food and Drug Administration (FDA) and other government agencies have approached the opioid crisis. METHODS/STUDY POPULATION: A PubMed search of “naloxone AND opioid overdose” with the filter “humans” was conducted to understand Naloxone’s regulatory framework. The term “naloxone” was searched on the Drugs@FDA: Approved Drug Products database. Additionally, “nalmefene” was searched on ClinicalTrials.gov. To examine the opioid antagonist market landscape, a PubMed search of “opioid antagonist AND opioid overdose” with the filters “humans” and “clinical trial,” and a ClinicalTrials.gov search of “opioid antagonist and opioid overdose,” were conducted. Government agency reports were reviewed and cataloged. RESULTS/ANTICIPATED RESULTS: Preliminary findings suggest a lack of innovation in the development of novel opioid antagonists. Most literature review findings focused on already-marketed Naloxone products, including the original injectable approved in 1971, the 2014 Evzio Auto-Injector, and the 2015 Narcan Nasal Spray (Figure 1). For example, there were 14 results yielded from the FDA approvals database, but none of these results represented a new opioid antagonist molecule. A longer-acting opioid antagonist, Nalmefene injectable, was approved in 1995 but has since been removed from the market due to low sales. Our initial ClinicalTrials.gov search using condition “opioid overdose” and other terms “opioid antagonist”,revealed no new studies being conducted on alternative opioid antagonist treatments for opioid overdose. Findings only focused on the distribution, co-dispensing, intervention, pharmacokinetics/pharmacodynamics (PK/PD) of Naloxone (Figure 2). However, a Google search yielded one new trial with an opioid antagonist by Opiant Pharmaceuticals, almost fifty years after FDA’s approval of Naloxone. A ClinicalTrials.gov search was then performed using the search term “nalmefene” to find whether Opiant Pharmaceuticals’ trial was in the ClinicalTrials.gov database. However, the Opiant trial is phase I, and as such does not require reporting on ClinicalTrials.gov. In 2017, the National Institutes of Health (NIH) launched an initiative for longer-acting opioid antagonist formulations. In 2018, Opiant Pharmaceuticals announced positive phase I results for intranasal Nalmefene. The potential return of Nalmefene in intranasal form may play a significant role in reducing overdoses, especially in cases where a longer-acting opioid antagonist is necessary. Opiant Pharmaceuticals’ trial commenced after the NIH announced their initiative; furthermore, the NIH’s National Institute on Drug Abuse granted the company $7.4 million to further the investigation of this drug. We will continue to research drugs that have previously been studied for the indication of treating opioid overdose in the United States and abroad and catalog them. DISCUSSION/SIGNIFICANCE OF IMPACT: The abuse and misuse of opioids in the United States has caused an epidemic accounting for over 115 opioid-overdose deaths each day, devastating our nation, both socially and economically. The United States spends $78.5 billion annually to combat the misuse of these drugs. Due to the severity of the opioid crisis, efforts to better understand approved therapies and investigational products in development to treat opioid overdose will be of significance moving forward. This research can inform agencies who are developing strategies to reduce opioid overdoses and pharmaceutical product developers about the current opioid antagonist landscape.
3567 An Analysis of Current Trends in Inclusion of Historically Underrepresented Populations in Clinical Trials: Women and Geriatrics
- Jacqueline Chen, Kaitlyn Park, Sun Young Uhm, Amelia Spinrad, Apurva Uniya, Nancy Pire-Smerkanich, Eunjoo Pacifici
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, pp. 83-84
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OBJECTIVES/SPECIFIC AIMS: Clinical trials (CTs) play an important role in developing new treatments, expanding or refining treatments that are already available, and/or identifying behavioral changes that can prolong or improve the lives of subjects. CTs are also conducted to understand normal human physiology, pathophysiology, and factors associated with health outcomes. Results from CTs are then used to determine the safety and efficacy of medications or treatment. CT participants should reflect the diversity of those receiving the treatments because, exclusion of specific populations in CTs may potentially result in knowledge gaps for clinicians and regulators. Historically, women and geriatrics have been underrepresented as CT participants. For women, this is the result of Food and Drug Administration (FDA) action in 1977 which restricted women with childbearing potential from participating in phase I and early phase II CTs after thousands of birth defects resulted from thalidomide usage during pregnancy. While the U.S. Government Accountability Office’s 1992 and 2001 reports documented an increased female inclusion in later stages of CTs, earlier phases of CTs were still lacking. Likewise, older adults and geriatrics have been excluded in CTs arbitrarily or to avoid adverse events associated with drug-drug interactions and comorbidities. Over the past few decades, the FDA has worked to address this issue and increase diversity and transparency in CTs. In 2015, the FDA’s Action Plan for Food and Drug Administration Safety and Innovation Act (FDASIA) Section 907 called for improved CT inclusion and reporting of demographic subgroups (sex, age, race, and ethnicity), highlighting three priority areas: quality, participation, and transparency. This research examines the current state of female inclusion in phase I and II CTs (2016 to 2017) and geriatric inclusion in phase III CTs (2010 to 2017). METHODS/STUDY POPULATION: To assess female representation in phase I and II CTs, data from 2016 CTs was extracted from clinicaltrials.gov. The average percentage of male and female participation in trials recruiting for males and females was determined; CTs conducted in only males or females (due to sex specific disease states) were excluded. The data was further differentiated into investigator-initiated and industry-sponsored trials to determine any differences in sex representation. Data from 2017 CTs on clinicaltrials.gov will be extracted and analyzed as well as 2016 to 2017 data from FDA novel drug approvals. To assess geriatric representation in phase III CTs, geriatric subsections of drug labels from novel drug applications approved between 2010 to 2017 were assessed for geriatric-specific information based on four areas: 1) reporting of CT including geriatrics, 2) reporting of percentage of CT participants ages 75+, 3) providing geriatric dosage recommendations, 4) determining product safety and efficacy for geriatrics. RESULTS/ANTICIPATED RESULTS: It is mandatory that all US CTs are registered on clinicaltrials.gov with the exception of Phase I studies, and results posted within 1 year of CT completion. In 2016, 916 phase I and 713 phase II CTs were registered on clinicaltrials.gov. Of these registered CTs, 4% of phase I and 9% of phase II CTs posted results. Of these, phase I studies included more males than females. Of these, phase I studies showed higher percentage of males (58%) than females (42%). In phase I/II, phase II, and phase II/III CTs, females were represented at a higher levels than males by 8-20% (Table 1). Phase I industry-sponsored and investigator-initiated trials and phase II/III investigator-initiated trials included less females than males (Table 2); all other types of CTs had more female than male subjects (Table 2). Preliminary findings will be expanded to include 2017 CTs and a wider pool of clinical trials will include all those associated with FDA novel drugs approved in 2016 and 2017. Of the 250 labels of novel drugs approved from 2010 to 2017 assessed for geriatric inclusion, 74% reported a CT including geriatrics, and 55% reported including CT participants ages 75+. Further, 31% provided geriatric dosage recommendations and 62% indicated insufficient evidence to determine product safety/efficacy for geriatrics (Figure 1). There was no consistent increase following the 2015 implementation of FDASIA section 907 in any of the four areas examined (Figure 2). Labels providing geriatric dosage recommendations were consistently the least fulfilled area across all years analyzed (Figure 3). DISCUSSION/SIGNIFICANCE OF IMPACT: A lack of inclusion of specific populations in CTs can lead to serious complications. For example, in 2013, the FDA required a lower recommended dose for women for drugs containing the sedative-hypnotic zolpidem (i.e. Ambien) due to persisting next morning drowsiness; the FDA arbitrarily recommended the dosage be halved from 10 mg to 5 mg as it found that women appeared to eliminate zolpidem from their bodies more slowly than men. Additionally, $35.7 million is spent annually on hospitalization from adverse drug reactions in the elderly. And, although government acts and initiatives have called for greater inclusion of certain populations like females and geriatrics in CTs, there is no penalty for exclusion. Problems like these may be avoided if these specific populations are included in CTs so that drugs can be properly studied. It may be preliminary to make conclusions about female representation in phase I clinical trials because it is not mandatory to register all phase I trials on clinicaltrials.gov, but further investigation will be conducted into FDA summary reports. Preliminary findings indicate that efforts to include female subjects may be effective in the subset of studies that reported their results. As of 2017, 51.3% of the U.S. population over 18 years old is female (U.S. Census Bureau). Early clinical trials often help to establish safety and dosing for phase III trials. Thus, it is pertinent that the inclusion rate is reflective of the general population at all clinical trial stages, not just pivotal, phase III trials. It would be prudent to monitor this trend as more studies report their results. Given that the average US life expectancy is now 78 years and that elderly population is expected to double in coming decades (NIH, 2016), there is an urgent need to include this population in current and future clinical research. Geriatrics, particularly those age 75+, use more than a third of total prescription and over-the-counter medications sold in US (Merck Institute, 2014), but is severely underrepresented in CTs. The effects of polypharmacy and changes in drug metabolism with age increase the need for specific drug dosage recommendations for geriatrics. As there was no discernable difference in drug labels fulfilling areas examined before and after 2015, FDASIA implementation may not have impacted geriatric inclusion in CT for drugs approved between 2010 to 2017. As many of these CTs began prior to FDASIA 2012 signing and 2015 implementation, the legislation’s full impact may occur in future years. Nonetheless, inadequate language currently found in geriatric drug labels can create challenges for clinicians when prescribing these medications for geriatric patients, potentially contributing to adverse drug events.
3080 Ensuring Quality in Investigator-Initiated Clinical Trials through Monitoring Concepts Training
- Amelia Spinrad, Nancy Pire-Smerkanich, Eunjoo Pacifici, Apurva Uniyal, Annie Xie, Annie Ly, Advaita Chandramohan
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- Journal:
- Journal of Clinical and Translational Science / Volume 3 / Issue s1 / March 2019
- Published online by Cambridge University Press:
- 26 March 2019, p. 117
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OBJECTIVES/SPECIFIC AIMS: Because clinical trial results are instrumental in the approval of a new drug or changes to the practice of medicine, ensuring the accuracy and validity of collected data is critical in the clinical trial process. This function, routinely carried out by clinical trial monitors in industry-sponsored trials, is often lacking in investigator-initiated trials (IITs) conducted in academia. To address this challenge, we have developed a self-study module that can be used to cross-train academic researchers in essential concepts and practical approaches to monitoring. Furthermore, we are applying a framework drawn from implementation science in the development and launch of this initiative. This framework, as used in other educational programs, is employed here to close the gap between initiative and practice, thereby effectively disseminating this training would improve the quality of clinical trials in academia. METHODS/STUDY POPULATION: This research project applied exploration, installation and implementation stages of the implementation science process by 1) exploring the need for a new initiative, 2) disseminating results, 3) engaging stakeholders, 4) creating standard operating procedures (SOPs) for installation and implementation, 5) studying user satisfaction and effectiveness, 6) addressing feedback and 7) conducting implementation. RESULTS/ANTICIPATED RESULTS: From literature review and internet searches we determined that although numerous GCP training resources exist, most are too broad and lack the practical approaches to meet the complex requirements of monitoring. Moreover, most of the offerings identified are costly or inaccessible. With only about 65% of IITs reported as being monitored (Figures 1 and 2), it appears that there is a clear need for training tools that are easily available to a broader audience. And because monitoring skills are substantially different from those associated with research coordination, it is not surprising that research professionals believed that they would need additional training to become proficient. To address this need, we began developing a monitoring module. We engaged key stakeholders from academia and industry to gain insights into their needs. The results indicated that although our training module was effective, supplementary information on the fundamentals of clinical trials should be included for those new to the field. After incorporating suggested changes and completing the module, we conducted user testing to determine if our module is ready to be broadly disseminated (Figures 3 and 4). Following positive feedback from the group, we are currently in the process of disseminating our module and studying its impact. DISCUSSION/SIGNIFICANCE OF IMPACT: IITs are instrumental in translating academic research into product development. Deficiencies in the quality control of these trials can lead to inadequacies in data accuracy and validity that could lead to significant delays in bringing innovative therapies to patients. Recent NIH policies require data and safety monitoring for all of the trials it supports. The latest addendum to ICH GCP, E6(R2), discusses a need for quality management across the clinical trial lifecycle. As we continue to disseminate and share information during the development of our self-study monitoring module, we are engaging key stakeholders from academia, government, and private institutions to understand and address quality challenges in conducting clinical trials. Finally, this research informs dissemination and implementation research, specifically for creating training for academic research professionals.