PriME-PGx: La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics

The implementation of clinical pharmacogenetics in daily practice is limited for various reasons. Today, however, it is a discipline in full expansion. Accordingly, in the recent times, several initiatives promoted its implementation, mainly in the United States but also in Europe. In this document, the genotyping results since the establishment of our Pharmacogenetics Unit in 2006 are described, as well as the historical implementation process that was carried out since then. Finally, this progress justified the constitution of La Princesa University Hospital Multidisciplinary Initiative for the Implementation of Pharmacogenetics (PriME-PGx), promoted by the Clinical Pharmacology Department of Hospital Universitario de La Princesa (Madrid, Spain). Here, we present the initiative along with the two first ongoing projects: the PROFILE project, which promotes modernization of pharmacogenetic reporting (i.e., from classic gene-drug pair reporting to complete pharmacogenetic reporting or the creation of pharmacogenetic profiles specific to the Hospital’s departments) and the GENOTRIAL project, which promotes the communication of relevant pharmacogenetic findings to any healthy volunteer participating in any bioequivalence clinical trial at the Clinical Trials Unit of Hospital Universitario de La Princesa (UECHUP).

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Distribution and geographic accessibility of prostate cancer clinical trials in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.4_suppl.59 ◽

2014 ◽

Vol 32 (4_suppl) ◽

pp. 59-59 ◽

Cited By ~ 2

Author(s):

Matt D. Galsky ◽

Asma Latif ◽

Kristian D. Stensland ◽

Erin L. Moshier ◽

Russell McBride ◽

...

Keyword(s):

Prostate Cancer ◽

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Geographic Distribution ◽

The United States ◽

First Line ◽

Trial Site ◽

Lorenz Curves ◽

Number Of Patients

59 Background: An extremely small proportion of patients with cancer in the United States (US) enroll in clinical trials. While several barriers to trial accrual have been described, the geographic distribution and accessibility of clinical trial sites has not been comprehensively explored. Methods: ClinicalTrials.gov was queried to identify all active US clinical trials exploring first-line therapies for metastatic prostate cancer (PCa) on 9/16/2012. We evaluated the geographic distribution of trial sites and determined the relationship between the number of sites and the number of patients with advanced PCa per county and evaluated heterogeneity using Lorenz curves. We also estimated the minimum driving distance required to access a clinical trial site from each ZIP code in the continguous US; a distance >30 miles was defined as high travel burden consistent with prior studies. Results: We identified 958 sites associated with 42 PCa clinical trials (Table). The geographic distribution of clinical trial sites was very inhomogeneous with several states having only 1-2 trial sites. Among 3185 US counties, 2,669 (83.8%) had no clinical trials available for first-line treatment of metastatic PCa. Counties with larger populations of patients with advanced PCa had significantly higher numbers of clinical trial sites. For every 100 additional patients with advanced PCa per county, the number of available trial sites increased by 21.0% (95% CI: 16.5-25.7%). However, Lorenz curves indicated a high degree of inequality in trial accessibility (Gini index 0.71). Approximately 31% of the US population resided >30 miles from a PCa trial site. Conclusions: Clinical trials sites are poorly accessible, geographically, to a large subset of US PCa patients, a finding that likely contributes to dismal accrual. Innovative solutions are required to address geographic barriers to access. [Table: see text]

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An Investigation into the Therapeutic Action of Hydroxyzine (Atarax) in the Treatment of Nervous Disorders and the Control of the Tobacco-Habit

Journal of Mental Science ◽

10.1192/bjp.104.436.826 ◽

1958 ◽

Vol 104 (436) ◽

pp. 826-833 ◽

Cited By ~ 7

Author(s):

G. C. Turle

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Side Effects ◽

Young Children ◽

Mental Hospital ◽

The United States ◽

Child Guidance Clinic ◽

Therapeutic Action ◽

Child Guidance

Hydroxyzine hydrochloride (Atarax, UCB 4492) is a tranquillizer which has attracted much interest in the United States, where it has undergone a series of clinical trials with encouraging results. In order to test the claims of American investigators a trial of hydroxyzine was made on a group of psychotic and psychoneurotic patients in a large mental hospital. The effectiveness of hydroxyzine in controlling the tobacco habit was also tested by using volunteer nurses at the hospital. Their observations provided useful information on the subjective action and side effects of the drug. A small number of young children attending a local child guidance clinic were also included in the clinical trial.

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Disparity in Clinical Trial Opportunities for Patients with B-Cell Malignancies in the United States

Blood ◽

10.1182/blood-2018-99-117155 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4861-4861

Author(s):

Sikander Ailawadhi ◽

Sri Lekha Bodepudi ◽

Zan Tahir Shareef ◽

Fabiola Coromoto Cardozo ◽

Salman Ahmed ◽

...

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Geographical Distribution ◽

Research Funding ◽

Phase 1 ◽

The United States ◽

Phase 2 ◽

B Cell Malignancies ◽

The Us

Abstract Background: Clinical trials are fundamental to advance therapeutics systematically and improve patient outcomes. Despite this, enrollment on clinical trials remains dismal in the United States (US) and is a constant focus of healthcare policy. We studied distribution of clinical trials for B-cell malignancies over time across the US and unique clinical trial opportunities i.e. individual clinical trials for the given diagnosis at a site that patients may have access to participate. Methods: We abstracted data from clinicaltrials.gov for all trials that had non-Hodgkin lymphoma (NHL) or multiple myeloma (MM) as an inclusion indication between 1999-2018. Clinical trial characteristics and distribution over US geographical divisions (West, Midwest, Northeast, and South) were studied, and differences were assessed by Chi-square test. Results: A total of 1930 trials were identified (NHL: 982, MM: 948), of which 483 were recruiting at the time of data abstraction (NHL: 250, MM: 233). Over the past 2 decades, 182691 patients were enrolled on the various trials (NHL: 81592, MM: 101099). Trials by phase of study included phase 1: 629, phase 1/2: 316, phase 2: 813, phase 2/3: 11 and phase 3: 161. Number of trials by phase separated by NHL and MM are shown in Figure 1. Of these, 197 trials were randomized (NHL: 67, MM: 130). Geographical distribution of trials by diagnosis type is shown in Figure 2. A total of 31806 unique trial opportunities were noted for MM and NHL, of which 9,513 were international and 22,293 were in the US, with a geographical distribution of 5080 in West, 8198 in Midwest, 3944 in Northeast, and 5071 in South. 4,883 of the unique trial opportunities were available at NCI/NCCN accredited sites and 17,410 were at non-NCI/NCCN sites in the US. Treatment characteristics of the trials included monoclonal antibodies in 1218, other targeted agents in 2641, stem cell transplant in 526, and other agents in 517 trials with several trials utilizing more than one of these therapeutic options. There was no statistically significant difference in the distribution of clinical trials by phase of study across various US geographical regions for MM (p=0.71), NHL (p=0.98) or combined MM+NHL (p=0.16). On the other hand, unique trial opportunities were significantly different by study phase and geographical distribution for MM, NHL or MM+NHL (all p<0.001) (Figure 3). Conclusions: Widespread access to clinical trials within a cancer diagnosis is imperative for generalizability of trial results. In a comprehensive, national analysis we noted that while it may appear that clinical trials are available across the US, sites where they are open are distributed unevenly, giving rise to a disparity in access to evidence-based therapeutic advancements for patients. Disclosures Ailawadhi: Janssen: Consultancy; Amgen: Consultancy; Pharmacyclics: Research Funding; Takeda: Consultancy; Celgene: Consultancy. Sher:Affimed: Research Funding.

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Clinical Trial Metrics: The Complexity of Conducting Clinical Trials in North American Cancer Centers

JCO Oncology Practice ◽

10.1200/op.20.00501 ◽

2020 ◽

pp. OP.20.00501

Author(s):

Carrie Lee ◽

Theresa L. Werner ◽

Allison M. Deal ◽

Cassandra J. Krise-Confair ◽

Tricia Adrales Bentz ◽

...

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

North America ◽

Clinical Research ◽

The United States ◽

Median Number ◽

Steering Committee ◽

Full Time ◽

Cancer Centers

PURPOSE: Cancer clinical trials offices (CTOs) support the investigation of cancer prevention, early detection, and treatment at cancer centers across North America. CTOs are a centralized resource for clinical trial conduct and typically use research staff with expertise in four functional areas of clinical research: finance, regulatory, clinical, and data operations. To our knowledge, there are no publicly available benchmark data sets that characterize the size, cost, volume, and efficiency of these offices, nor whether the metrics differ by National Cancer Institute (NCI) designation. The Association of American Cancer Institutes (AACI) Clinical Research Innovation (CRI) steering committee developed a survey to address this knowledge gap. METHODS: An 11-question survey that addressed CTO budget, accrual and trial volume, full-time equivalents (FTEs), staff turnover, and activation timelines was developed by the AACI CRI steering committee and sent to 92 academic cancer research centers in North America (n = 90 in the United States; n = 2 in Canada), with 79 respondents completing the survey (86% completion rate). RESULTS: The number of FTE employees working in the CTOs ranged from 4.5 to 811 (median, 104). The median number of analytic cases (ie, newly diagnosed or received first course of treatment) reported by the main center was 3,856. Annual CTO budgets ranged from $250,000 to $23,900,000 (median, $8.2 million). The median trial activation time, based on 61 centers, was 167 days. The median number of accruals per center was 480 (range, 5-6,271) and median number of trials per center was 282 (range, 31-1,833). Budget and FTE ranges varied by NCI designation. CONCLUSION: The response rate to the survey was high. These data will allow cancer centers to evaluate their CTO infrastructure, funding, portfolio, and/or accrual goals as compared with peers. A wide range in each of the outcomes was noted, in keeping with the wide variation in size and scope of cancer center CTOs across the United States and Canada. These variations may warrant additional investigation.

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Toward a Jurisprudence of Drug Regulation

The Journal of Law Medicine & Ethics ◽

10.1111/jlme.12139 ◽

2014 ◽

Vol 42 (2) ◽

pp. 244-262 ◽

Cited By ~ 2

Author(s):

Matthew Herder

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Medical Devices ◽

Phase 1 ◽

Clinical Trial Data ◽

The United States ◽

Trial Data ◽

Regulatory Decisions ◽

Clinical Study Reports

Efforts to ensure greater transparency in the regulation of “drugs” (used here as a catch-all for pharmaceuticals, biologics, medical devices, and biomarker-based technologies such as genetic testing paired with a pharmaceutical or biologic) are well underway. For example, laws in the United States and Europe now require registration of most clinical trials beyond phase 1. Yet instances of avoidable harm to patients continue to arise. In response, calls for disclosure of clinical trial data in the form of “clinical study reports,” not just trial designs and basic results, are growing. In this paper, I argue that disclosure of clinical trial data is necessary but insufficient. Rather, the regulatory decisions that flow from those trial data —whether positive (i.e., product approvals) or negative (i.e., abandoned products, product refusals, and withdrawals) —should also be open to outside scrutiny provided they are final in nature.

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Pancreatic Cancer Clinical Trials and Accrual in the United States

Journal of Clinical Oncology ◽

10.1200/jco.2013.49.4823 ◽

2013 ◽

Vol 31 (27) ◽

pp. 3432-3438 ◽

Cited By ~ 32

Author(s):

William A. Hoos ◽

Porsha M. James ◽

Lola Rahib ◽

Anitra W. Talley ◽

Julie M. Fleshman ◽

...

Keyword(s):

United States ◽

Pancreatic Cancer ◽

Clinical Trial ◽

Clinical Trials ◽

Supply And Demand ◽

The United States ◽

Disease Stage ◽

Ductal Adenocarcinoma ◽

Cancer Clinical Trials ◽

Cancer Trials

Purpose Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Methods Pancreatic cancer–specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. Results The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Conclusion Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

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Colon Cancer: The Exclusion of Native Americans and Hispanics from Clinical Trials in the United States

10.31219/osf.io/rx95f ◽

2021 ◽

Author(s):

Joseph Angel De Soto

Keyword(s):

United States ◽

Clinical Trial ◽

Colon Cancer ◽

Clinical Trials ◽

African Americans ◽

Native Americans ◽

The United States ◽

Cancer Clinical Trial ◽

Cancer Clinical Trials ◽

Trial Participants

Abstract:Introduction: Each year there are 150,000 new cases of colon cancer in the United States. The chance of death for Hispanics and Native Americans who get colon cancer is much higher than whites even though both groups are much less likely to get colon cancer than whites. In this study, we look at the inclusion or exclusion of Hispanics and Native Americans from colon cancer clinical trials. Methods: In this retrospective study, 48 colon cancer clinical trials in the United States with an aggregate of 421,530 participants performed within the last ten years were selected at random. These clinical trials were evaluated for the inclusion and exclusion of minorities. Results: Though whites make up only 60.1% of the population they make up 89% of the colon cancer clinical trial participants. African Americans, and Hispanics who make up 13.4% and 18.5% of the population only made up 5.6% and 0.6% of the colon cancer clinical trial participants. Only two native Americans out of 421,530 colon cancer clinical trial participants could be identified. Conclusion: Colon Cancer Clinical trials have systematically excluded Hispanics and Native Americans while minimizing the participation of African Americans. This may be directly related to the increased death rates seen in these groups and provides evidence for the non-generalizability of colon cancer clinical trials.

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A community-centered approach to sickle cell disease and clinical trials participation: an evaluation of perceptions, facilitators, and barriers

Blood Advances ◽

10.1182/bloodadvances.2020003434 ◽

2021 ◽

Author(s):

LaTasha H Lee ◽

LaShanta H Whisenton ◽

Jasmine Benger ◽

Sophie Lanzkron

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Sickle Cell Disease ◽

Clinical Research ◽

Sickle Cell ◽

Treatment Options ◽

The United States ◽

Personal Health Information ◽

Cell Disease

Sickle cell disease (SCD) is the most common inherited red blood cell disorder in the United States, affecting 70,000-100,000 Americans and causing a range of serious medical complications. Although the cause of SCD was established decades ago, existing therapies have varied effectiveness and side effects, and novel therapies have been slow to develop. The limitations of existing treatment options highlight the need for new therapies that are aligned with the desires of the community. To date, little has been done to systematically seek and report the opinions and experiences of people with SCD regarding clinical research. In 2019, the American Society of Hematology Research Collaborative (ASH RC) conducted eight community workshops across the United States engaging 472 people, including persons with SCD and caregivers of those living with the disease. The workshop goals included assessing understanding, awareness, and perceptions of clinical research; and identifying the most critical clinical trial considerations of this community. Participants were asked about their experiences living with SCD and their satisfaction with treatment options. Pain and fatigue were reported as symptoms requiring better therapies. Although few participants reported being asked to enroll in a clinical trial, they expressed conditional willingness to participate. A majority were willing to share personal health information to further research and improve health outcomes. To actively engage the SCD community and increase enrollment and retention in clinical trials, researchers should address the treatment priorities of this population and ensure they have access to trusted information about clinical research and opportunities for participation.

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Abstract 154: A Comparison of Carotid Artery Stent Placement Performed Within and Outside Clinical Trials in the United States

Stroke ◽

10.1161/str.43.suppl_1.a154 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Haitham M Hussein ◽

Saqib A Chaudhry ◽

Shahram Majidi ◽

Rakesh Khatri ◽

Gustavo J Rodriguez ◽

...

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Hospital Mortality ◽

Stent Placement ◽

The United States ◽

Cardiac Events ◽

Hospital Outcomes ◽

End Point ◽

National Cohort

Background: A discrepancy between characteristics of patients treated with carotid angioplasty and stent placement (CAS) within and outside clinical trials, particularly characteristics with direct impact on clinical outcome, may lead to reduction in anticipated benefit. Objective: To identify differences in demographic and clinical characteristics and outcomes related to CAS in patients treated within clinical trials and those treated outside clinical trials in a large national cohort. Methods: We determined the frequency of CAS performed within and outside clinical trials and associated in-hospital outcomes using data from the Nationwide Inpatient Survey (NIS) data files from 2005 to 2008. All the in-hospital outcomes were analyzed after adjusting for potential confounders using multivariate analysis. Results: Of the 47,899 patients who underwent CAS, 16,078 (1%) underwent the procedure as part of a clinical trial. The mean age of the patients was significantly lower in patients treated with CAS as part of a clinical trial than those treated with CAS outside a clinical trial. The proportion of women and non-whites was lower among patients treated with CAS as part of a clinical trial. The in-hospital mortality was two folds higher among patients treated with CAS outside clinical trial (1.12% versus 0.53%, p=0.0.0005). The rate of composite end-point of stroke, cardiac events, and death was significantly higher among patients treated with CAS outside clinical trials (p=0.02). After adjusting for age, gender, presence of hypertension, diabetes mellitus, renal failure, congestive heart failure, and hospital teaching status, CAS performed as part of clinical trial was associated with lower rates of in-hospital mortality (OR 0.349, 95% CI 0.219-0.555)(p<0.0001) and composite end point of stroke, cardiac events, and death (OR 0.349, 95% CI 0.219-0.555)(p<0.0001) . Conclusions: Our results suggests that CAS performed as part of clinical trial was associated with lower rates of in-hospital mortality and composite end point of stroke, cardiac events, and death in United States. These findings highlight the need for strategies that ensure appropriate adoption of CAS to ensure that the benefits observed in clinical trials can be replicated in general practice.

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Patient advocacy organizations’ information for patients on pre-approval access to investigational treatments

BMC Research Notes ◽

10.1186/s13104-019-4745-7 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Kelly McBride Folkers ◽

Sarah Leone ◽

Arthur Caplan

Keyword(s):

United States ◽

Clinical Trial ◽

Clinical Trials ◽

Drug Administration ◽

Patient Advocacy ◽

The United States ◽

Patient Access ◽

Advocacy Organizations ◽

Lack Of Information ◽

The U.S

Abstract Objective To evaluate the availability of information regarding patient access to investigational treatments through clinical trials and non-trial pre-approval access pathways from a sample of patient advocacy organization (PAO) websites in the United States. Results We systematically analyzed the content of 118 randomly selected PAO websites to assess whether they contained information on clinical trials and non-trial pathways—e.g., the U.S. Food and Drug Administration (FDA) expanded access (EA) program and right to try—over the course of two months from February to March 2019. A majority (81%, n = 96) of PAOs provided a link to ClinicalTrials.gov, and 73% (n = 86) had their own clinical trial finder or list of relevant trials. 23% (n = 27) mentioned EA, with 8% (n = 9) providing specific resources for FDA’s EA program. 8% (n = 10) provided a statement on the passage of the federal right to try law. A majority of PAO websites contained information on clinical trials, but a minority discussed non-trial pre-approval access. The lack of information on the latter highlights an area in need of improvement.

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