key: cord-0838618-jjt5nnsv authors: Piciocchi, Alfonso; Messina, Monica; Soddu, Stefano; La Sala, Edoardo; Paoloni, Francesca; Giuliani, Giorgia; Marino, Martina Rachele; Petrelli, Claudia; Gorreo Renzulli, Livia; Fazi, Paola; Vignetti, Marco title: COVID‐19 pandemic and management of GIMEMA clinical trials: changes and challenges date: 2020-07-04 journal: Br J Haematol DOI: 10.1111/bjh.16996 sha: a18e34ec971f76e8104bd5836763ec157b0cd0fb doc_id: 838618 cord_uid: jjt5nnsv With the outbreak of COVID‐19 pandemic (Wang et al, 2020), Italy ‐ and in particular the largest Northern regions ‐ became disease epicenter with a dramatic raise in infections and deaths in the month of March. This article is protected by copyright. All rights reserved necessity, closure of all non-essential shops. The healthcare system was put under pressure and healthcare professionals faced a variety of changes and challenges involving also the conduct of clinical We collected 136 surveys (74.3% response rate). The list of respondent PIs is provided in Supplementary Table 1 and their geographic distribution is depicted in Supplementary Fig 1. The main changes in the management of patients occurred in the conduct of visits. Indeed, the latter that were converted into phone/video visits -as answered by 56.3% of PIs -, postponed (52.6% of PIs) or This article is protected by copyright. All rights reserved cancelled (25.4% of PIs); home nursing was only marginally (6%) implemented. These alternatives, though preventing the discontinuation of the trial, are not devoid of risks that may derive from delays in the scheduled visits, differences with in-person visits, incomplete visit data. Reassuringly, halt of trial sites was a rare event (3.8% of PIs) and trial site closure was not reported ( Fig 1A) . Moderate changes occurred in the execution of laboratory tests with 20% of PIs who declared that the centralization of laboratory tests was not carried out and 12.7% who reported a transfer of laboratory tests in a different location (Fig 1A) . The PIs commented that the service was preserved mainly by storing the samples or performing the tests locally. Notwithstanding, these different procedures may result in lack of uniformity in sample processing and affect assay results. In the section dedicated to protocol specific questions, we queried about minimal residual disease quantification that, according to a low number of respondents (8% of LAL2317 PIs, 17.4% of LAL2116 PIs), was not regularly performed. A discontinuation of such a pivotal activity may lead to an inadequate disease monitoring and compromise the achievement of the primary objective of the studies. Nevertheless, to draw definitive conclusions, it is warranted to go beyond aggregated data and analyze patients' data: to this purpose, GIMEMA is collecting COVID-19 related information in dedicated Case Report Forms (CRFs). An alarming data came from the analysis of new enrollments: indeed, starting from April we registered a decline equal to 25% that continued also in May, when restrictive measures were released. This data indicates that the effect of constraints may last beyond the months of lockdown (Fig 1B) . The PIs ascribed this reduction to the stay-at-home measures that produced a reduction of first visits and diagnostic tests. This issue may have an impact on sample size and may introduce selection biases towards the patients with severer symptoms that require access to hospitals. With regards to the workload, almost half of PIs judged as mild the burden the study-staff had to bear. Performing visits was reported as the most frequent problem the study-staff had to face (42.6% of PIs), followed by filling CRFs (22.8% of PIs) and complying with the protocol (15.4% of PIs, Fig 2A) , hence indicating the likelihood of missing/delayed data and protocol deviations. From patients' standpoint, 13.4% of PIs reported the cancellation of visits by patients, thus indicating some difficulties/reluctancies in visiting hospitals. This occurred and especially in the trials for chronic leukemias, thus mirroring an effect of the disease status. Notably, even during this emergency, the psychological support was preserved (Fig 2B) . The measures to moderate the spread of infections to study-staff included: limitation of access to public places (81.5% of PIs), smart-working for data managers (79.9% of PIs), self-isolation/quarantine of the This article is protected by copyright. All rights reserved staff (51.5% of PIs, Fig 2C) . The comparison of the regions with the highest number of deceased patients with the others revealed that the strategies adopted were homogenous. Detailed results are described in Supplementary data and Supplementary Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on May 14th, 2020 Gestione degli studi clinici in Italia in corso di emergenza COVID-19 (coronavirus disease 19 Available from: EMA Guidance on the Management of Clinical Trials during the COVID-19 (Coronavirus) pandemic Version Available from: FDA Guidance on Conduct of ClinicalTrials of Medical Products during COVID-19 Public Health Emergency. Guidance for Industry, Investigators, and Institutional Review Boards R: A language and environment for statistical computing. R Foundation for Statistical Computing Research electronic data capture (REDCap) -A metadata-driven methodology and workflow process for providing translational research informatics support The REDCap consortium: Building an international community of software platform partners COVID-19 in persons with haematological cancers Adaptive trial designs: a review of barriers and opportunities Preserving Clinical Trial Integrity During the Coronavirus Pandemic Treating Leukemia in the Time of COVID-19. Acta Accepted Article This article is protected by copyright Impact of COVID-19 on oncology clinical trials EHA Infectious Disease Scientific Working Group & Hans H. Hirsch. Frequently asked questions regarding SARS-CoV-2 in cancer patients-recommendations for clinicians caring for patients with malignant diseases A novel coronavirus outbreak of global health We thank Prof. Robin Foà who encouraged this study and all the PIs who devote time to complete the survey during an unprecedented medical challenge. AP designed research, analyzed data and wrote the manuscript; MM interpreted results and wrote the manuscript; SS, ELS and FP planned and designed surveys; GG, MRM, CP, LGR collected and managed surveys; PF and MV designed research and critically revised the manuscript. The authors do not have conflicts of interest to disclose. This article is protected by copyright. All rights reserved