key: cord-0971518-rj8bj9s1 authors: Ives, Amy; Pusztai, Tricia; Keller, Jacqui; Ahern, Elizabeth; Chan, Bryan; Gasper, Harry; Wyld, David; Kennedy, Glen; Dickie, Graeme; Lwin, Zarnie; Roberts, Natasha A. title: Resilience and ongoing quality care for cancer clinical trials during COVID‐19: Experience from a tertiary hospital in Australia date: 2021-04-05 journal: Asia Pac J Clin Oncol DOI: 10.1111/ajco.13570 sha: 40a673aa638b047efb3a96aeede73c805155af9a doc_id: 971518 cord_uid: rj8bj9s1 BACKGROUND: The COVID‐19 pandemic has forced rapid system‐wide changes to be implemented within cancer care at an alarming pace. Clinical trials are a key element of comprehensive cancer care. Ensuring the continuing safe conduct of cancer clinical trials in the context of a pandemic is challenging. METHODS: We aimed to describe the COVID‐19 pandemic response of a Cancer Care Clinical Research Unit (CRU) of a tertiary hospital in Queensland, Australia. We used a mixed methods approach for this case study. Emailed directives from CRU managers to all CRU staff sharing were qualitatively analysed and mapped against our unit activities over longitudinal time points. Data from patient recruitment and protocol deviations were analysed using descriptive statistics. RESULTS: Mapping activity from 11 March to 30 September 2020 revealed rapid change during the first 2 weeks. Four key strategies to accommodate change were identified: supporting patients and families, introduction of telehealth, accessing investigational product, and social distancing. Early in the pandemic we recognised that our core key stakeholders were integral to our response. When compared to the previous 12 months, our recruitment numbers dropped markedly in early phases of the response but recovered over time, as we accommodated internal and external impacts. CONCLUSION: Our experience of agility as a necessity, adapting to support patients, and managing both clinical research activity and sponsors during the height of the pandemic response is presented here in order to inform future disaster response planning by clinical trial organisations. SARS-CoV-2, a novel coronavirus which causes the disease known as COVID-19, was identified in the Wuhan providence of China in December 2019. 1 A pandemic was declared by the World Health Organisation (WHO) on 11 March 2020. Australia's COVID-19 incidence curve began to rise sharply and alarmingly during the second week of March 2020, at which time government bodies across the country mobilised, to prepare for the crisis that was predicted to potentially overwhelm our health systems. 2 Cancer clinical research units and triallists around clinical trial integrity where possible. [3] [4] [5] In April 2020, the US Food and Drug Administration released pandemic guidance on conduct of clinical trials prioritising participant safety and encouraged communication between various stakeholders with an emphasis on maintaining protocol consistency and clear documentation. 6 Here, we describe our CRU response to the COVID-19 pandemic as a case study, to capture the real-time adaptations made to achieve outcomes consistent with these guidelines. We used a mixed methods approach 7 to describe the events of COVID-19 and subsequent response by our Cancer Care Services' Clinical Research Unit (CCS CRU) between 11 March and 30 September 2020. Retrospective data sets were accessed for historical reference to compare and complement our findings. 8 The study site was the Royal Brisbane and Women's Hospital (RBWH), a major referral centre and tertiary teaching hospital in South East Queensland, Australia. The RBWH is situated in Brisbane but also services patients across the state and from neighbouring New South Wales. The CCS CRU consists of three clinical trials groups: medical oncology, radiation oncology, and haematology and bone marrow transplant (BMT). There are a total of 30 (full or part-time) staff which consists of clinical trial coordinators, administrative staff, and a manager for each of the three groups. The CCS CRU is co-located on campus with both inpatient and outpatient cancer services and implements a model that embeds clinical research into day-to-day care provision. We used three sets of data to describe the impact and response to the pandemic including (i) emailed directives from CCS CRU managers providing COVID-19-specific updates to CCS CRU staff, (ii) data reports of patient recruitment, and (iii) study commencement and study closeout data from our clinical research unit database. The time period of quantitative datasets was from January 2019 until September 2020. Qualitative data from above email directives were collated to map the response 9 from 11 March 2020 until 30 September 2020. Review of correspondence within the CCS CRU for qualitative analysis Correspondence was also independently coded by three investigators (AI, TP, and NR) and then organised into themes using qualitative methods. 10 Investigator AI is a senior clinical trial coordinator in medical oncology malignancies with 10 years of trials experience, TP is a senior clinical trial coordinator in haematology malignancies with 10 years of trials experience, and NR is a clinician researcher with 10 In Queensland, the initial pandemic response commenced on 12 March 2020. The qualitative mapping identified the initial very rapid pandemic response in the first 2 weeks. The timeline of events are presented in Figure 1 The response to COVID-19 required engagement with key stakeholders. Four key stakeholder groups were identified ( Figure 2 A thematic analysis of the above-stated emailed correspondence identified four key areas where decisions and changes were systematically targeted. The CCS Executive had quickly developed a formal response strategy across the service line, with specific directives for the CCS CRU. Regular meetings between CCS CRU managers, principal investigators/researchers, and executive were held to discuss and plan an actionable approach. A three-phase pandemic response plan was drafted by the CCS CRU managers, with input sought by executive leadership to determine a structured decision-making framework for trial recruitment, thereby facilitating trial continuity where safe and feasible ( Phase one of the response was implemented immediately, with the second phase projected to start within 2 weeks. This plan also comprised of (i) the identification of participants who should attend in-person trial-related activities, (ii) those who could have trial protocol-mandated visits conducted remotely (e.g. by telehealth), or (iii) those who could cease trial-related activities temporarily or permanently. All decisions were communicated to trial participants proactively so that patients could assess the impact and appropriate supports could be established. After the initial drafting of this plan, CCS Executive, CCS CRU managers, and principal Investigators/researchers met regularly to decide on how to respond to the most recent changing landscape of the pandemic. As soon as the WHO declared the pandemic, patients started contacting clinical research staff to discuss their treatment plans, with approximately 20 additional queries per day. A practical plan for patients who declined to attend the site in-person due to the fear of COVID-19 infection was needed as a priority. Standardised support and information resource tools were developed within a week to address patients' self-identified existential con- Staff were required to work under social distancing guidelines as per health service directives and workspaces were individually assessed. The area designated for clinical trial monitors was reallocated, allowing additional room for CRU staff to limit crowding in shared offices. Dividing barriers were constructed between desks. Uptake of virtual meetings was initially challenging due to a lack of equipment, such as webcams or headsets. Staff struggled with the different virtual meeting platforms but adjusted with time. Eventually all meetings became virtual because usual meeting rooms did not allow sufficient space to meet social distancing requirements, and larger rooms were over-subscribed. Monthly data for patient recruitment were assessed (Figure 3 ). Responding to change: Beyond week 2 of the pandemic The external factors Over time, it became apparent that the feared COVID-19 infection rates had not occurred as predicted. In May 2020, the CCS CRU began to welcome Queensland-based CRAs back to site in-person under a new set of processes developed to accommodate COVID-19 restrictions. This was a new challenge as there were no shared guidelines between the contracted CRAs, HRECs, and RGO. With a new monitoring space already in place, a more formal process was developed with strict time slots for monitoring. CCS CRU staff could no longer sit together with CRAs in the same desk space to answer queries. Instead larger rooms (which were in short supply) had to be booked to hold discussions or Microsoft Teams was used as an alternative. CRAs had to complete a screening checklist to confirm travel, contacts, and symptoms prior to attending site. CCS CRU staff shared information about federal, state, and local guidance to ensure requirements remained current and responsive to the contemporary nature of national and international conduct of clinical trials. Recruitment holds instituted at site were fully lifted in May, and by June all studies were open and operating except for one. In late June, Queensland announced a roadmap to reopen its state borders, although international borders remained closed. Flights began to increase again, making it easier for regional patients to attend the study site. Responding to the second wave of COVID-19 infection rates On 30 June 2020, a second wave of COVID-19 cases in Melbourne occurred. There was also increasing concern for community transmission in Brisbane, which triggered another lockdown. Tiers of response from our hospital health service fluctuated dynamically to manage the impact of infection rates emerging in the local community. The CCS CRU guidelines from the early rapid response to the pandemic were reevaluated and re-instituted. Most importantly, the first wave preparation phase had helped us to now quickly identify key stakeholders and their needs, and how to most effectively share information effectively. The rapid movement of change during the COVID-19 pandemic has been widely published. 11 The mapping of CCS CRU data also illuminates a rapid rate of response during initial preparations of the pandemic response. The phenomenal pace of change in 2 weeks would have normally taken at least a year. Scientific literature has now made recommendations for the triage of cancer treatment, albeit at a later stage of the pandemic and not in real time. The decisions made in the CCS CRU to manage the tiers of response were consistent with these recommendations. 2, [12] [13] [14] United interdisciplinary teams such as investigators, CCS CRU staff, clinicians, and health administrators were a success, and this is discussed in the wider literature as having a greater importance during COVID-19. [12] [13] Such success is likely due to the established relationships and trust built over time. Interestingly, Nabhan et al. 3 identify that one of the major changes during this period has been the way sponsors and CROs have dealt with the reduction in frequency of monitoring and the changes to patient's visits, and have led to a more practical approach. Importantly, this has not appeared to be a major restriction to patient recruitment. Sponsors or CROs were either monitoring less frequently or to a reduced percentage of data. 3 The impact of local health teams needing to respond quickly to external decisions has also been widely reported in the literature. 11 Patient recruitment was affected during the height of the pandemic response in March 2020. Beyond that, recruitment rates increased again showcasing our ability to adjust and minimise the impact to studies. Studies that continued beyond this time were assessed on an individual basis with stakeholder consultation. Trial participants were very anxious they would not be able to access treatment and similar concerns from the broader oncology patient population are also reported in the international literature. 13 The use of multiple datasets makes the findings of this case study robust to inform our response to the pandemic and compare with previous benchmarks. However, this study is limited in that it is a single- During the pandemic, sponsors have become more flexible with study procedures. As a result, research has become more patient focussed whilst ensuring safety and treatment continuity. Patients who live in regional areas have been allowed to have assessments performed with their local medical practitioner, local laboratory, or local imaging provider with the CCS CRU staff and investigator oversight. The impact of this on trial outcome evaluation and data collection will be assessed, but if feasible could provide convenient alternatives for future trial conduct. Other pandemic adaptations which might be suitable for more widespread adoption include the use of electronic signatures for patient consent forms using telehealth consent processes. Other Our final reflection of our lived experience as CRU staff is that we were confidently able to continue quality care and data collection, sustaining and meeting local and regulatory requirements, during an unprecedented crisis. Presenting our case study may give other units who are currently navigating much larger COVID-19 infection rates a reference point to assist during this challenging time. It is apparent that we are more adaptable to change than we gave ourselves credit for. In the face of an unprecedented crisis, we came together, for our patients, to provide the best possible outcomes. Clinical characteristics and risk factors associated with COVID-19 disease serverity in patients with cancer in Wuhan, China: a multicentre retrospective cohort study Practical considerations for treating patients with cancer in the COVID-19 pandemic Rethinking clinical trials reform during the COID-19 pandemic Implciations for design and analyses of oncology clinical trials during the COVID-19 pandemic Preserving clinical trial integrity during the coronavirus pandemic Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemics Mixed methods research is an effective method of enquiry for community health research Toward a conceptual framework for mixed-method evaluation designs Timeline mapping in qualitative interviews: a study of resilience with marginalized groups Qualitative Data Analysis COVID-19 and cancer: current challenges and perspectives Oncology care delivery in the COVID-19 pandemic: an opportunity to study innovations and outcomes Oncology practice during the COVID-19 pandemic Cancer care in the time of COVID-19: a conceptual framework for the management of cancer during a pandemic Implementation of the Australasian teletrial model: lessons from practice Resilience and ongoing quality care for cancer clinical trials during COVID-19: experience from a tertiary hospital in Australia The authors want to thank Annette Cubitt, Robyn Western, and Danni Church for assistance in collating data.