E-Consent - a guide to implement an innovative solution to maintain recruitment in clinical trials during the COVID-19 pandemic

Introduction: The COVID-19 pandemic has posed daunting challenges for the conduction of clinical research. Adopting new technologies such as remote electronic consent (e-Consent) can help overcome them. However, guidelines for e-Consent implementation in ongoing clinical trials are currently lacking. The NeuroSAFE PROOF trial is a randomised clinical trial evaluating the role of frozen section analysis during RARP. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this study is to describe the process of implementation, impact on recruitment rate and patients' experience using e-Consent. Methods: A substantial amendment of the protocol granted the creation of a remote e-Consent framework based on the REDCap environment, following the structure and content of the already approved paper consent form. A new pathway was developed which offered continuous support to patients through remote consultations. Results: Before the first recruitment suspension, NeuroSAFE PROOF was recruiting an average of 9 patients per month. After e-Consent implementation, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old Methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. Limited troubleshooting has been required after implementation. Conclusions: Remote e-Consent based recruitment was critical for the continuation of the NeuroSAFE PROOF trial during the COVID-19 pandemic. The described pathway complies with ethical and regulatory guidelines for informed consent, while minimizing face-to-face interactions that increase the risk of COVID-19 transmission.

NeuroSAFE PROOF. Update on a multi-centre, pragmatic, RCT for men undergoing robot-assisted radical prostatectomy: Trial in progress

Introduction & Objectives: Robot-assisted Radical Prostatectomy (RARP) is an effective cure for organ confined prostate cancer but is associated with considerable post-operative functional toxicity. The NeuroSAFE technique (intra-operative frozen section analysis of the neurovascular structure adjacent margin) may help improve functional outcomes by promoting optimal nerve-sparing (NS) RARP without compromising on oncological outcomes. NeuroSAFE technique has reported favourably in retrospective, single-centre studies but has never been evaluated prospectively by a randomised study. The NeuroSAFE PROOF Feasibility Study has succeeded in demonstrating feasibility and has been succeeded by the fully powered, definitive NeuroSAFE PROOF Randomized Controlled Trial (RCT) (NCT03317990). Materials & Methods: Potent men (IIEF-5>21) with localised prostate cancer at 4 regional uro-oncology centres in the UK (UCLH, Bristol, Sheffield and Glasgow) are eligible. Participants are randomised 1:1 to RARP with NS decision guided by standard of care (clinical information, DRE and pre-operative mpMRI surgical plan) vs. RARP with NS decision guided by standard of care information and the NeuroSAFE technique. The primary outcome is erectile function (EF) recovery assessed by IIEF-5 score at 12-months. Important secondary outcomes include detailed peri-operative outcomes, histological outcomes, post-operative complications, biochemical recurrence rates, urinary continence (assessed by ICIQ), health related quality of life (assessed by Rand-36 and EQ-5D-5L), and health economics. In order to demonstrate a difference of 15% in EF recovery rates between the arms, a total of 404 men will be randomised and treated. Patient follow-up will continue for 5 years after RARP. Results: At the time of writing, 160 men have been recruited and treated with RARP as per random allocation at 4 participating sites. The independent DMC has met twice to ensure the oncological safety of the trial and will continue to review the data at intervals. Covid-19 has led to significant challenges, including suspension of recruitment and difficulties performing follow-up. The trial team have developed new methods of recruitment, consent and follow-up to ensure conduct of the study remains in line with the highest standards of trial conduct, including electronic remote consent processes and remote collection of PROMs. Conclusions: The NeuroSAFE technique has been reported as a method to optimise outcomes for men undergoing RARP for over a decade, but, in the absence of Level 1 evidence, equipoise remains. Despite the Covid-19 pandemic recruitment continues to be favourable. We hope that our

E-Consent – an innovative solution to maintain recruitment momentum in clinical trials during the COVID-19 pandemic

Introduction & Objectives: The NeuroSAFE PROOF trial is an ongoing randomized clinical trial evaluating the role of frozen section analysis during robot assisted radical prostatectomy for localized prostate cancer. In response to the COVID-19 crisis, recruitment was halted, and a remote e-Consent solution was designed. The aim of this is to describe the implementation, impact on recruitment rate and patient’s experience using e-Consent. Materials & Methods: To replace in person consent. An email-based PDF Auto-Archiver feature was created within the Research Electronic Data Capture (REDCap®) environment, following the structure and content of the already approved paper consent. Each question was included as a binary (yes/no) field. An electronic signature field allows the participant to sign the document using a mouse, stylus, or their finger. The signature is captured and appended as a PNG image with a timestamp. This allows research staff to review and electronically co-sign and lock the document. This new tool was approved by the Health Research Authority, Research Ethics Committee, Trial Management Group and Sponsor. Owing to the process collecting patient identifiable data, the platform resides within the REDCap service being hosted behind a Data Safe Haven, which conforms to National Health Service Data Security & Protection Toolkit, General Data Protection Regulation and ISO 27001 Information Security standards. Results: Before recruitment suspension, the trial was recruiting an average of 9 patients per month, with an increasing trend. (Figure 1) After e- Consent implementation in June 2020, 63 new patients (4/month) have been enrolled despite a second lockdown, none of whom would have been recruited using the old methods given restrictions on face-to-face consultations. Patients have given positive feedback on the use of the platform. The use of this pathway eliminates the need to travel and, therefore, the resultant cost and potential risk of infection, while allowing patients to read and understand information in their own time before providing consent. (Figure Presented) Conclusions: Guidelines for e-Consent implementation are currently lacking. We present the first description of its use for prostate cancer research. This innovation was critical to resume recruitment for the NeuroSAFE PROOF trial and will be essential for planning future research.

Neurosafe proof: A multi-centre, pragmatic, RCT for men undergoing robot-assisted radical prostatectomy. update on a trial in progress

INTRODUCTION AND OBJECTIVE: Robot-assisted Radical Prostatectomy (RARP) is an effective cure for organ confined prostate cancer but is associated with considerable post-operative functional toxicity. The NeuroSAFE technique (intra-operative frozen section analysis of the neurovascular structure adjacent margin) may help improve functional outcomes by promoting safe nerve-sparing (NS) RARP without compromising on oncological outcomes. NeuroSAFE technique has reported favourably in retrospective, single-centre studies but has never been evaluated prospectively by a randomised study. The NeuroSAFE PROOF Feasibility Study has succeeded in demonstrating feasibility and has facilitated opening of the full-scale, definitively powered NeuroSAFE Randomized Controlled Trial (RCT) (NCT03317990). We report on the design and progress of the full NeuroSAFE PROOF RCT. METHODS: Potent men (IIEF-5>21) with localised prostate cancer at 4 regional uro-oncology centres in the UK (UCLH, Bristol, Sheffield and Glasgow) are eligible. Participants are randomised 1:1 to RARP with NS decision guided by standard of care (clinical information, DRE and pre-operative mpMRI surgical plan) vs. RARP with NS decision guided by standard of care information and the NeuroSAFE technique. The primary outcome is erectile function recovery assessed by IIEF-5 score >15 at 12-months. Important secondary outcomes include detailed peri-operative outcomes, histological outcomes, post-operative complications, biochemical recurrence rates, urinary continence (assessed by ICIQ), and health related quality of life (assessed by Rand-36 and EQ-5D-5L). Aiming to demonstrate a difference of 15% in erectile function recovery rates between the arms, a total of 404 men will need to be randomised and treated. Patients will continue to be followed for outcomes until 5 years after treatment. RESULTS: At the time of writing, 159 men have been recruited and treated with RARP as per random allocation at the 4 participating sites. The independent DMC has met thrice to ensure the oncological safety of the trial and will continue to review the data at intervals. Covid-19 has led to significant challenges, including suspension of recruitment and difficulties performing follow-up. The trial team have developed new methods of recruitment, consent and follow-up to ensure conduct of the study remains in line with the highest standards of trial conduct. CONCLUSIONS: The NeuroSAFE technique has been reported as a method to optimise outcomes for men undergoing RARP for over a decade, but, in the absence of level 1 evidence, equipoise remains. We hope that our full trial (the first RCT of the NeuroSAFE technique in the world) will provide the evidence to establish whether what has long been a promising technique truly improves outcomes for men undergoing RP.

Is Arbitration Helping or Hindering the Protection of the Environment and Public Health?

On the occasion of the sixth edition of the Casablanca Arbitration Days, some leading arbitration practitioners from the Middle Fast and North Africa (MENA) region and further afield convened to discuss an important and topical issue: 'is arbitration helping or hindering the protection of the environment and public health?'. This conference examined the various areas where arbitration and the protection of the environment and public health interface. First, from a substantive view point, it is clear that environmental issues have become prevalent in commercial arbitration and that the latter has proven to be well suited to resolve such issues. Secondly, while some steps have already been taken in this respect, the climate change crisis requires the international arbitration community to change its ways and arbitrate in a much more environmentally friendly way. Thirdly, amidst the progressive emergence of environmental issues in investment arbitration and the responses that have already been provided by investment treaty arbitral tribunals, numerous uncertainties remain in respect of the way in which environmental issues should be treated. There is no doubt that environmental issues will give rise to intense debates before investment tribunals (and courts) and in legal literature in the near fusture. Finally, in addition to the protection of the environment, the arbitration community has already begun addressing (and, we would submit, successfully so) the substantive and procedural issues related to the protection of public health, in particular as a result of the COVID-19 global pandemic. This article provides an account of what was said about these various topics during this edition of the Casablanca Arbitration Days.