An industry survey of implementation strategies for clinical supply chain management of cell and gene therapies.

BACKGROUND AIMS: The novelty of cell and gene therapies (CGTs) has introduced unique supply chain challenges and considerations not seen by chemically synthesized (small-molecule) drugs. These complexities increase during the clinical phases, where drug safety and efficacy milestones are still underdeveloped. For example, for autologous therapies such as chimeric antigen receptor T-cell therapies, in which the treatment is developed from the patient's own cells, supply chain management plays an integral role in chemistry, manufacturing and control processes. Supply chain management requires proactive planning because of the strict cold chain requirements and time sensitivity of CGTs. This research examines strategies and responses to challenges experienced by industry stakeholders (e.g., sponsors and manufacturers) during the implementation phases of clinical supply chain management. This research further evaluates the adequacy of the current regulatory framework for distribution and supply chain management of CGTs in the US. METHODS: A survey methodology was used to query subject matter experts from the biopharmaceutical industry who were familiar with the clinical supply management of CGTs in the US. The survey instrument was developed using an implementation framework and disseminated electronically to mid- and senior-level subject matter experts who had experience with clinical trials, supply chain management and CGTs. RESULTS: A total of 128 respondents accessed the survey, and 105 respondents answered at least one question. Seventy-five respondents completed the survey. Results showed that a lack of harmonization in regulations across the supply chain, limited resources, challenges with vendor management, high costs and complexities in the supply chain due to product specificity and customization proved to be impediments for the industry. In addition, the coronavirus disease 2019 pandemic had a significant impact on supply chain implementation. The results revealed that less than half of the respondents had business continuity plans in place. These challenges increased for smaller and mid-size organizations. Thirty percent of small and mid-size organizations were less prepared to scale up than larger companies. CONCLUSIONS: Suggestions from industry stakeholders were to adopt and enforce Good Distribution Practices in the US (81%), pre-plan distribution strategies with internal and external stakeholders along the supply chain and develop agile systems and robust processes end to end. Hurdles in scaling up and scaling out from the clinical to commercial phases for time- and temperature-sensitive CGT products make it difficult to predict the supply chain's long-term feasibility. Although there are initiatives to improve these impediments, such as improving industry partnerships and creating global CGT transportation standards, there are still regulatory knowledge gaps present for CGTs. Therefore, it is essential to establish a baseline and foundation for CGT supply chains extending beyond the loading dock.

Screening for distress and needs: Findings from a multinational validation of the Adolescent and Young Adult Psycho-Oncology Screening Tool with newly diagnosed patients.

OBJECTIVE: Adolescents and young adults (AYAs) diagnosed with cancer commonly experience elevated psychological distress and need appropriate detection and management of the psychosocial impact of their illness and treatment. This paper describes the multinational validation of the Distress Thermometer (DT) for AYAs recently diagnosed with cancer and the relationship between distress and patient concerns on the AYA-Needs Assessment (AYA-NA). METHODS: AYA patients (N = 288; 15-29 years, Mage  = 21.5 years, SDage  = 3.8) from Australia (n = 111), Canada (n = 67), the UK (n = 85) and the USA (n = 25) completed the DT, AYA-NA, Hospital Anxiety Depression Scale (HADS) and demographic measures within 3 months of diagnosis. Using the HADS as a criterion, receiver operating characteristics analysis was used to determine the optimal cut-off score and meet the acceptable level of 0.70 for sensitivity and specificity. Correlations between the DT and HADS scores, prevalence of distress and AYA-NA scores were reported. RESULTS: The DT correlated strongly with the HADS-Total, providing construct validity evidence (r = 0.65, p < 0.001). A score of 5 resulted in the best clinical screening cut-off on the DT (sensitivity = 82%, specificity = 75%, Youden Index = 0.57). Forty-two percent of AYAs scored at or above 5. 'Loss of meaning or purpose' was the AYA-NA item most likely to differentiate distressed AYAs. CONCLUSIONS: The DT is a valid distress screening instrument for AYAs with cancer. The AYA-POST (DT and AYA-NA) provides clinicians with a critical tool to assess the psychosocial well-being of this group, allowing for the provision of personalised support and care responsive to individuals' specific needs and concerns.

Clinical findings and outcomes of MRI staging of breast cancer in a diverse population.

BACKGROUND: The performance of magnetic resonance imaging (MRI), the effect of patient factors, and resulting surgical management in underserved and ethnically diverse breast cancer (BC) patient populations have been understudied. METHODS: We retrospectively analyzed the data of 1116 consecutive patients who were newly diagnosed with in situ or invasive BC with preoperative staging MRI. Non-index lesions (NILs) were defined as abnormal MRI findings with BI-RADS score of 4 or 5 in breast or axillary nodes not previously detected by conventional imaging. Occult cancers (OCs) were NILs found to be malignant by biopsy or surgery. Logistic regression was used to examine associations between probabilities of NILs or OCs and patient characteristics. RESULTS: Staging MRI detected NILs and OCs in 24% and 7.5% of patients, respectively. Of 1116 patients, 271 (24%) had 327 NILs, and 84 (7.5%) had 87 OCs. Follow-up information was available for 306 NILs. Ipsilateral breast NILs (n = 124) were seen in 115 patients (10.3%), with OCs (n = 51) seen in 48 patients (4.4%). Contralateral breast NILs (n = 134) were seen in 118 (10.6%) patients, with OCs (n = 20) seen in 20 patients (1.8%). Laterality (p < 0.001) and disease stage (p = 0.018) were associated with probability of OC. Patients without BRCA mutations had a significantly higher probability of having NILs (p = 0.003) but not OCs. CONCLUSIONS: Our study provides useful estimates of the rates of NILs and OCs anticipated in a younger, uninsured, ethnically diverse population. Prospective trials and larger pooled retrospective analyses are needed to define the long-term impacts of MRI staging after a BC diagnosis.

Value of routine staging imaging studies for patients with stage III breast cancer.

BACKGROUND AND OBJECTIVES: Routine staging imaging studies (RSIS) are optional in stage III breast cancer (BC). The impact of RSIS on treatment decisions and patient outcomes has not been extensively studied. The goal of this study was to determine whether RSIS in stage III BC affected treatment or patient outcomes. METHODS: Stage III BC patients from 2000 to 2010 were retrospectively identified. RSIS results and treatment plan in response to RSIS results were recorded. Univariate and multivariate Cox proportional hazards regression models with time-dependent covariates were used to assess associations between RSIS use and recurrence-free survival (RFS). RESULTS: Of 420 patients, 362 (86.2%) received RSIS. RSIS were negative in 264 (72.9%), indeterminate in 77 (18.3%), and positive in 21 patients (5.0%) for metastatic disease. Treatment was altered in 21 (5.8%) patients based on RSIS results (20 with metastatic disease, 1 with indeterminate disease). There was no difference in RFS with RSIS use on multivariate analysis (hazard ratio 1.3; 95% confidence interval 0.73-2.5, P = 0.32). CONCLUSIONS: Most stage III BC patients underwent RSIS, but RSIS results infrequently affected treatment decisions. There was no significant difference in RFS with RSIS use. RSIS to identify metastatic disease for stage III BC has limited value. J. Surg. Oncol. 2016;114:917-921. © 2016 Wiley Periodicals, Inc.

Pharmacy undergraduate programs: Development of an adaptive curriculum for student success.

Objectives: Applicants for graduate work in Pharmacy on paper appear competitive, but upon entering a Doctor of Pharmacy (PharmD) program many students struggle with course work, course load, and pharmacologic topics in their first-year studies. In addition to math and science, undergraduate candidates need to have skills that enable them to be adaptable and creative learners. The Pharmacy Undergraduate Program (PUP) at the University of Southern California (USC) has been attentive to these educational needs. In this manuscript we will show how our program has been successful in generating well-prepared and successful candidates for graduate programs (pharmaceutical, clinical, medical, and other) and employment in pharmaceutical fields. Methods: A review of current student enrollments (N = 121), graduated student annual survey data (N = 50), student research data (N = 68), and ongoing course surveys have been used to detail information related to PUP. Results: Students who have graduated from PUP have been successful post-graduation. Graduates of PUP have gone on to PharmD programs 44% (22/50); medical school 16% (8/50); PhD programs 24% (12/50); full-time employment 6% (3/50); internship/volunteer positions 10% (5/50); taken a gap year 4% (2/50); and MS/MA program 2% (1/50). Conclusions: PUP has been successful in helping the admission of our students into graduate degree programs related to pharmaceutical sciences and medicine. This success can be attributed to the dynamic nature of the course offerings and the creativity of the teaching faculty, which leads to students being well-prepared to tackle the rigors of their graduate studies after leaving the program.

Graduate Training Capacity for Regulatory Professionals at US Universities: Are We Facing a Talent Crisis?

BACKGROUND: Talent acquisition in regulatory affairs has been a continuing challenge now exaggerated by demographic shifts and expansion of regulatory requirements nationally and globally. METHODS: Survey and interview methods were used to provide information on graduation rates, graduate characteristics, and enrollment trends in the 17 US regulatory programs that could be identified to offer graduate degrees in regulatory affairs or regulatory science. RESULTS: US programs graduated approximately 522 MS and 4 doctoral students in 2018. About 70% of students attended programs in the Northeast; the remaining students were evenly split between programs in the Northwest and Southeast/Southwest. About half of the programs provided content by distance only. About 127 students were new entrants to the workforce; enrollments for this group most commonly leveled or decreased over the last 3 years. The primary challenge identified by most programs was the high tuition that discouraged participation by qualified candidates for the programs. Challenges were also reported when attracting international students because of tightening visa restrictions and consequent reluctance of industry to hire students with a temporary visa status. CONCLUSIONS: The small number of graduating regulatory professionals from US universities is alarming because it falls far short of needs estimates for positions in regulatory departments. The particularly low number of entry-level professionals seems unlikely to be adequate as unemployment rates tighten and experienced professionals become harder to attract. These shortfalls may be particularly hurtful to small companies unable to compete for experienced professionals.

Biobank Continuity Management: A Survey of Biobank Professionals.

Academic biobanks face challenges that call for continuity and disaster planning. However, current regulations do not require such planning, so it is unclear if and how biobanks have prepared themselves to deal with future crises. This exploratory study used mixed methods to understand the state of continuity planning in U.S. biobanks. It first reviewed the current state of regulatory and implementation requirements that drive and challenge continuity planning. A survey instrument was then developed and critiqued by a focus group of experienced practitioners in biobanking. The refined survey was disseminated to a targeted group of respondents employed at biobanks across the United States. Most respondents were associated with relatively mature biobanks in operation for more than 6 years and these typically had some form of continuity plan in place. More commonly, continuity planning was reported to be focused on countering natural disasters rather than organization- or personnel-related crises. Respondents identified their most common limitation to be financial resources affecting all phases of implementation. Although many respondents appeared to be aware of some guidance documents and standards for continuity planning, many reported that they did not use or reference them when constructing their biobank continuity plans. Furthermore, nearly 25% of surveyed biobanks did not have a continuity plan and 61% indicated concern in having a mandated continuity plan. Results suggested academic organizations would benefit from a continuity plan template and best practice guidelines for plan development and implementation.

Escalation of oncologic services at the end of life among patients with gynecologic cancer at an urban, public hospital.

PURPOSE: Use of oncology-related services is increasingly scrutinized, yet precisely which services are actually rendered to patients, particularly at the end of life, is unknown. This study characterizes the end-of-life use of medical services by patients with gynecologic cancer at a safety-net hospital. METHODS: Oncologic history and metrics of medical use (eg, hospitalizations, chemotherapy infusions, procedures) for patients with gynecologic oncology who died between December 2006 and February 2012 were evaluated. Mixed-effect regression models were used to test time effects and construct usage summaries. RESULTS: Among 116 subjects, cervical cancer accounted for the most deaths (42%). The median age at diagnosis was 55 years; 63% were Hispanic, and 65% had advanced disease. Only 34% died in hospice care. The median times from do not resuscitate/do not intubate documentation and from last therapeutic intervention to death were 9 days and 55 days, respectively. Significant time effects for all services (eg, hospitalizations, diagnostics, procedures, treatments, clinic appointments) were detected during the patient's final year (P < .001), with the most dramatic changes occurring during the last 2 months. Patients with longer duration of continuity of care used significantly fewer resources toward the end of life. CONCLUSION: To our knowledge, this is the first report enumerating medical services obtained by patients with gynecologic cancer in a large, public hospital during the end of life. Marked changes in interventions in the patient's final 2 months highlight the need for cost-effective, evidence-based metrics for delivering cancer care. Our data emphasize continuity of care as a significant determinant of oncologic resource use during this critical period.