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Same-Day Consent for Regional Anesthesia Clinical Research Trials: It's About Time.

Diversity and Inclusion in Pancreatic Cancer Clinical Trials

The clinical trials that are conducted by the National Cancer Institute (NCI) represent the core of the clinical program of the NCI’s Center for Cancer Research. At the Center for Cancer Research, clinical and basic science are integrated with the goal of reducing the burden of cancer through discovery, exploration, and bench-tobedside translational treatment and prevention modalities. The goal of the NCI clinical trials program is to answer questions about particular cancers and to identify new therapeutic and prevention interventions, which are performed across the United States at centers participating in NCI-supported research. Sadly, only 2% to 7% of adult patients with cancer across the United States participate in these clinical trials. To make matters worse, the following populations are under-represented among participants in NCI-funded clinical trials: Latinos/Hispanics, Asian and Pacific Islanders, African American men, American Indians/Alaskan Natives, adolescents, older adults (age 65 years), individuals who reside in rural areas, and individuals of low socioeconomic status. The lack of diversity in clinical trials populations reduces the opportunity for discovering effects that may be relevant to a particular under-represented population. The literature has focused on barriers to participation in clinical trials—including both physician and patient issues—such as cost, lack of support personnel, limited access to clinical trials, and the distance that patients may live from centers that participate in NCI clinical trials. In a study by Meropol et al, cognitive, affective, and practical barriers to participation in clinical treatment trials were characterized among Pennsylvania oncologists. Eligible physician participants were practicing medical oncologists in Pennsylvania, and eligible patients were adults at least 18 years of age with cancer undergoing follow-up by medical oncologists in Pennsylvania. Of 137 oncologists and 170 patients who completed the surveys, of patients, 84% were aware of clinical trials, and both oncologists and patients generally agreed that clinical trials were important to improve cancer treatment. It was interesting that oncologists and patients in this report were more likely to consider clinical trials in advanced or refractory disease. When considering seven potential barriers to clinical trials, random assignment and fear of receiving a placebo were highly ranked by both patients and oncologists. Patients identified fear of adverse effects as the greatest barrier to clinical trial participation, whereas oncologists ranked this psychosocial barrier as of least importance to their patients. Although the study found that oncologists and patients in Pennsylvania were aware of clinical trials and had favorable attitudes toward them in principle, psychosocial barriers existed for patients that more than likely reduced participation. One of the key issues in this study was the fact that the oncologists who were surveyed had favorable attitudes toward clinical trials. Surely, there must be oncologists who don’t have favorable attitudes toward clinical trials and are not advocates of clinical trials. This is reflected in the fact that 30% of oncologists are responsible for 70% of the accrual to NCI clinical trials. Although some important pragmatic issues, such as fiscal and administrative support, may affect participation, these are issues that affect all oncologists to varying degrees, yet some oncologists are more successful than others in accruing patients to clinical trials. As reported by the Coalition of Cooperative Groups, community-based practices are responsible for 64% of adult patients accrued in cooperative group–sponsored clinical trials. Academic centers are responsible for 34%, whereas military/Veteran’s Administration hospitals contribute the remaining 2%. Hence, the NCI Community Clinical Oncology Programs (CCOPs) play a major role in adult recruitment to NCI-sponsored clinical trials. Created in 1983 by the National Cancer Institute, the CCOP network allows patients and physicians to participate in state-of-the-art clinical trials for cancer prevention and treatment in their local communities. There are 50 CCOPs and 13 minority-based CCOPs currently funded in 35 states across the United States, the District of Columbia, and Puerto Rico. The Delaware Christiana CCOP was initially funded in 1987. After a restructuring of the cancer program at the Helen F. Graham Cancer Center at Christiana Care in 2001, accrual to NCI clinical trials increased from 9.9% in 2001% to 20% in 2006. There are many reasons for this dramatic increase in clinical trial accrual over a 5-year period, which represents six times the national average. All the reasons for this increase in patient accrual to NCI clinical trials are beyond the content of this article. Briefly, however, this increase has been partly due to the establishment of multidisciplinary disease site centers, placing clinical research nurses in the private practice offices, with a continuous marketing campaign. Nevertheless, despite the improvement of this clinical trials accrual, there is a core of physicians participating in the cancer program whose track record to clinical trial accrual can best be described as dismal. This is despite the fact that there are more than 110 clinical trials available for their patients covering every disease site, with personnel support to help in the recruitment to clinical trials. These individuals are designated members of the NCI Cooperative Groups and many have membership in cooperative groups on their curriculum vitaes. Some investigators have suggested that access to clinical trials should be an objective and a component of state-of-the-art cancer JOURNAL OF CLINICAL ONCOLOGY COMMENTS AND CONTROVERSIES VOLUME 26 NUMBER 15 MAY 2

Informed Consent

Access to data from clinical trials in the COVID-19 crisis: open, flexible, and time-sensitive

COVID 19 has brought race disparities to the forefront as part of a national dialogue and upset. Those of us that are people of color or do research in this space are not surprised. The reality is that despite the numerous reports and efforts that have so keenly highlighted race disparities and recommendations to address them, we have yet to truly move the needle to improve the health of black and brown people. Interestingly, COVID 19 has caused a national pivot among funding agencies to add research around COVID-19 to their current funding portfolios as enhancement awards or RFAs specific to the pandemic, quickly emerged requiring a rapid response. The value and need for this pivot given this monumental time in global health history is necessary. Yet to what extent are we thinking carefully and deliberately about the importance of diversity in our clinical research and trials to ensure our findings positively impact the populations who are hardest hit and carry the greatest burden of the disease, namely African Americans and other people of color. This a fundamental question and poses an opportunity for us to do something different than what has been our historical pattern. It is well documented that a lack of diverse participation in clinical research and trials is a national problem, where in most studies disproportionally engage white men and women more than any other race and ethnic group. For example, in a recent publication the authors found that 96% of prostate cancer research study participants are white men, in a disease in which black men have the highest incidence and mortality than any other race and ethnic group. National studies engage thousands of patients in clinical research, trials, registries and biobanks but on average have less than 20% of participants from underrepresented race and ethnic groups. This is a far cry from national representation of race and ethnic groups of color and has clear implications that in essence perpetuates the disparities we seek to reduce or eliminate. Lack of diversity in research participation limits our ability to accelerate research and improve population health more broadly. For example, it limits generalizability of findings from the development of effective therapeutics to dissemination and implementation of evidence-based methods to increase screening, treatment, and quality of care are critical, all critical points care points highlighted by COVID-19. It excludes or limits access to cutting edge and potentially life-saving therapies that may have the potential to ease the burden of disease and death for people of color. Essentially, access to clinical research and trials is a social justice and an equity issue and without deliberate and intentional diversity strategies being initiated as we develop and design studies, we are adding to the ongoing sickness and death or preventable diseases among people who are black and brown, this particularly true in the case of COVID 19, cancer and other chronic diseases. While diversity in clinical trials to improve population health and advance racial equity is critical, COVID 19 has presented added challenges and opportunities to address the lack of diversity in oncology clinical research, trials, and biobanking. The very nature of a pandemic requires rapid response, action with a heightened sense of urgency, and some would argue, fear of the unknown. Add these key factors to the well-known points that influence lack of diversity in clinical trials including race and ethnic minorities not being asked or informed about clinical trials, assumptions made by research teams that suggest implicit biases, lack of an overarching diversity strategy embedded in recruitment strategies, lack of accountability -despite the requirement to complete the minority enrollment table, and a paucity of authentic community and stakeholder partnerships that have the ability to build trust and bolster diversity in clinical research before, during and post the pandemic and across an array of diseases, the outcomes could seem dismal. However, addressing these key elements can yield invaluable outcomes, namely improved health and quality of life, preventing avoidable deaths, and equity. This presentation provides key recommendations to advance equity and move the needle in increasing diversity in oncology clinical research and trials, a national imperative. Citation Format: Nadine J. Barrett. The Compelling Imperative to Diversify Participation in Clinical Trials and Research [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA02.

Outsourcing Big Pharma

Previous abusive clinical trials have caused several obstacles in recruiting African Americans for clinical trials today. The memory of the Tuskegee Syphilis Study alone remains a hard pill to swallow and is a constant hindrance to recruiting potential African Americans specifically males, for clinical trials. The basic trust that African Americans have for physician researchers, U.S. government doctors, U.S. government-sponsored research, and biomedical research in general has been seriously, although not irrevocably, breached. The purpose of this study was to gain an understanding of the knowledge, attitudes, and beliefs African Americans have that support decisions to either participate or not participate in a clinical trial. Specific areas that were examined by perceptual and demographic measures included: knowledge of clinical research processes, perceptions of clinical research purposes and procedures, advantages and disadvantages for the individual of participation in clinical research trials, characteristics of current and past participation in clinical research trials, exposure to selected experiences which are preliminary to participation in clinical research trials, perceptions regarding the need for selected changes in preparation for participation in clinical research trials; and selected personal demographic characteristics: gender, age, marital status, education level, employment status, household income, distance from research center, and overall health status. The survey method was utilized in this study. The discriminant analysis model was used to determine if a model existed that significantly increased the researcher's ability to correctly classify volunteers on their participation status in clinical research trials. The overall model was meaningful and successful in correctly classifying 74.6% of the original grouped cases. The strongest findings suggest that African Americans are likely to participate in future clinical trials based on their knowledge and perceptions of clinical research trials. Principal Investigators and research teams which focus on African Americans in clinical research trials should therefore place an increased emphasis on strategic planning that involves participants representative of the study population. To yield results, the plan should be tailored to African Americans, presented as a credible study, designed to reflect trust in the medical care team, and implemented through a continuous educational process.

ABSTRACTAimTo explore Australian hospital pharmacy services provided to clinical drug trials in 2007; and to compare the results with data from similar surveys conducted in 1989 and 1994.MethodQuestionnaires were sent to pharmacy managers of 301 public and private Australian hospitals.Results164 hospitals responded to the survey. The response rate (55%), demographics and number of hospitals conducting clinical drug trials (75%) did not differ significantly in 1989, 1994 and 2007. However, the number of hospital pharmacies reporting 30 or more clinical drug trials had more than tripled between 1989 (n = 11) and 2007 (n = 38). From 1994 to 2007 there was a 300% increase in the number of pharmacy departments who reported spending 20 hours/week or more on clinical trials. In 1994 and 2007, pharmacy departments with 30 or more clinical trials reported that they had a dedicated clinical trials pharmacist. By 2007, most hospital pharmacies (70%) were funded for over 50% of their clinical trials; a significant increase from 5% in 1989 and 32% in 1994. Most hospital pharmacies (78%) dispensed more than 75% of the investigational drugs within their hospitals. Pharmacist involvement in the review of trial protocols by membership of institutional human research ethics committees had tripled between 1989 (n = 14) and 2007 (n = 43).ConclusionSpecialisation and expertise to conduct clinical drug trials by hospital pharmacists is recognised by their increased involvement with human research ethics committees, increased funding to pharmacies, more specialist clinical trial pharmacists, and pharmacists dispensing drugs for clinical trials conducted in hospitals.

Principles from clinical trials relevant to clinical practice: Part II.

Mitigating Administrative Risks in Industry-sponsored Clinical Trials

(99m)Tc-Annexin A5 has been used as a molecular imaging probe for the visualization, characterization and measurement of apoptosis. In an effort to define the quantitative (99m)Tc-annexin A5 uptake criteria that best predict tumor response to treatment, we performed a systematic review and meta-analysis of the results of all clinical imaging trials found in the literature or publicly available databases. Included in this review were 17 clinical trials investigating quantitative (99m)Tc-annexin A5 (qAnx5) imaging using different parameters in cancer patients before and after the first course of chemotherapy and/or radiation therapy. Qualitative assessment of the clinical studies for diagnostic accuracy was performed using the QUADAS-2 criteria. Of these studies, five prospective single-center clinical trials (92 patients in total) were included in the meta-analysis after exclusion of one multicenter clinical trial due to heterogeneity. Pooled positive predictive values (PPV) and pooled negative predictive values (NPV) (with 95% CI) were calculated using Meta-Disc software version 1.4. Absolute quantification and/or relative quantification of (99m)Tc-annexin A5 uptake were performed at baseline and after the start of treatment. Various quantitative parameters have been used for the calculation of (99m)Tc-annexin A5 tumor uptake and delta (Δ) tumor changes post-treatment compared to baseline including: tumor-to-background ratio (TBR), ΔTBR, tumor-to-noise ratio, relative tumor ratio (TR), ΔTR, standardized tumor uptake ratio (STU), ΔSTU, maximum count per pixel within the tumor volume (Cmax), Cmax%, absolute ΔU and percentage (ΔU%), maximum ΔU counts, semiquantitative visual scoring, percent injected dose (%ID) and %ID/cm(3). Clinical trials investigating qAnx5 imaging have included patients with lung cancer, lymphoma, breast cancer, head and neck cancer and other less common tumor types. In two phase I/II single-center clinical trials, an increase of ≥25% in uptake following treatment was considered a significant threshold for an apoptotic tumor response (partial response, complete response). In three other phase I/II clinical trials, increases of ≥28%, ≥42% and ≥47% in uptake following treatment were found to be the mean cut-off levels in responders. In a phase II/III multicenter clinical trial, an increase of ≥23% in uptake following treatment was found to be the minimum cut-off level for a tumor response. In one clinical trial, no significant difference in (99m)Tc-annexin A5 uptake in terms of %ID was found in healthy tissues after chemotherapy compared to baseline. In two other clinical trials, intraobserver and interobserver measurements of (99m)Tc-annexin A5 tumor uptake were found to be reproducible (mean difference <5%, kappa = 0.90 and 0.82, respectively) and to be highly correlated with treatment outcome (Spearman r = 0.99, p < 0.0001). The meta-analysis demonstrated a pooled positive PPV of 100% (95% CI 92 - 100%) and a pooled NPV of 70% (95% CI 55 - 82%) for prediction of a tumor response after the first course of chemotherapy and/or radiotherapy in terms of ΔU%. In a symmetric sROC analysis, the AUC was 0.919 and the Q* index was 85.21 %. Quantitative (99m)Tc-annexin A5 imaging has been investigated in clinical trials for the assessment of apoptotic tumor responses. This meta-analysis showed a high pooled PPV and a moderate pooled NPV with ΔU cut-off values ranging between 20% and 30%. Standardization of quantification and harmonization of results are required for high-quality clinical research. A standardized uptake value score (SUV, ΔSUV) using quantitative SPECT/CT imaging may be a promising approach to the simple, reproducible and semiquantitative assessment of apoptotic tumor changes.

The goal of this study was to examine the effect of a rural community clinical oncology program-based cancer-care intervention program that was launched to increase the number of rural patients with cancer enrolled in clinical trials. Five rural counties in eastern North Carolina served as intervention communities, and five rural counties in South Carolina served as the comparison region. The intervention counties used a rapid tumor-reporting system, a nurse facilitator who identified and prompted oncologists to enter patients into clinical trials, a quarterly newsletter to primary-care physicians about cancer treatment and clinical trials, and a health educator who focused on community-wide education regarding cancer prevention, treatment, and clinical trial information. Outcomes included changes in knowledge and attitudes about clinical trials among the primary-care providers who were surveyed and enrollment in clinical treatment trials for breast and colorectal cancer, as analyzed by comparing practice pattern data from before and after the intervention. The results indicate that the intervention was not effective. The proportion of primary-care physicians who were aware of clinical trials for their patients with cancer rose slightly in comparison counties (26% to 34%) but remained constant (41% to 43%) in intervention counties. Perceived patient and actual physician barriers toward clinical trial participation were reported by the physicians. A minority of potentially eligible patients with breast or colon cancer in both North Carolina and South Carolina were enrolled in clinical trials. These data suggest that different types of interventions may be needed to improve accrual to cancer treatment trials in rural communities. In addition, the role that primary-care providers play in encouraging patients with cancer to participate in clinical treatment trials needs further exploration.

Treating the Black Hypertensive in 2010: Achieve Lower Targets While Awaiting More Definitive Evidence

A Comprehensive Analysis of Institutional and Nationwide Datasets Identifies Key Parameters that Influence Racial Minority Enrollment onto Clinical Trials