Remote preenrollment checking of consent forms to reduce nonconformity.

BACKGROUND: In biomedical research, the signed consent form must be checked for compliance with regulatory requirements. Checking usually is performed on site, most frequently after a participant's final enrollment. PURPOSE: We piloted a procedure for remote preenrollment consent forms checking. We applied it in five trials and assessed its efficiency to reduce form nonconformity before participant enrollment. METHODS: Our clinical trials unit (CTU) routinely uses a consent form with an additional copy that contains a pattern that partially masks the participant's name and signature. After completion and signatures by the participant and investigator, this masked copy is faxed to the CTU for checking. In case of detected nonconformity, the CTU suspends the participant's enrollment until the form is brought into compliance. We checked nonconformities of consent forms both remotely before enrollment and on site in five trials conducted in our CTU. We tabulated the number and nature of nonconformities by location of detection: at the CTU or on site. We used these data for a pseudo before-and-after analysis and estimated the efficiency of this remote checking procedure in terms of reduction of nonconformities before enrollment as compared to the standard on-site checking procedure. We searched for nonconformity determinants among characteristics of trials, consent forms, investigator sites, and participants through multivariate logistic regression so as to identify opportunities for improvement in our procedure. RESULTS: Five trials, starting sequentially but running concurrently, with remote preenrollment and on-site checking of consent forms from 415 participants screened in 2006-2009 led to 518 consent forms checked; 94 nonconformities were detected in 75 forms, 75 (80%) remotely and 19 more (20%) on site. Nonconformities infrequently concerned dates of signatures (7%) and information about participants (12%). Most nonconformities dealt with investigator information (76%), primarily contact information (54%). The procedure reduced nonconformities by 81% (95% confidence interval (CI): 73%-89%) before enrollment. Nonconforming consent forms dropped from 25% to 0% over the period, indicating a rapid learning effect between trials. Fewer nonconformities were observed for participants screened later in a trial (odds ratio (95% CI): 0.5 (0.3-0.8); p = 0.004), indicating a learning effect within trials. Nonconformities were more common for participants enrolled after screening (2.4 (1.1-5.3); p = 0.03), indicating a stricter scrutiny by form checkers. LIMITATIONS: Although our study had a pseudo before-and-after design, no major bias was identified. Power and generalizability of our findings were sufficient to support implementation in future trials. CONCLUSIONS: This procedure substantially limited nonconformity of consent forms with regulatory requirements before enrollment, thus proving a key component of a risk-based monitoring strategy that has been recommended to optimize resources for clinical research.

Preserving participant anonymity during remote preenrollment consent form checking.

BACKGROUND: In biomedical research, the consent form must comply with regulatory requirements. Checking for compliance typically has been performed on-site and most frequently after a participant's final enrollment. We use a procedure for remote preenrollment checking of consent forms that protects participant identities. This procedure requires a copy of the consent form that partially masks the fields for participant's name and signature; this copy is faxed to the clinical trials unit for checking. PURPOSE: To describe our efforts to identify an appropriate printed masking pattern. We tried several patterns that permit ascertainment of the presence of signatures and names and evaluated each one with respect to degree of masking participant identities. METHODS: We assessed the efficiency of a satisfactory pattern through an experiment. We created forms with variants of the masking pattern on the copy to be faxed. We completed the forms with fictitious identities before copies were faxed and checked by clinical research associates. We measured the rate of empty and filled fields detected and the rate of letters and names correctly read. The target was defined as 100% for the rate of empty and filled fields detected and 0% for the rate of letters and names correctly read. RESULTS: The best masking pattern allowed the detection of 100% empty and filled fields and the reading of 0% names and 19% letters. Consequently, the consent form with the selected masking pattern has been used routinely in our clinical trials unit. LIMITATIONS: We tested only five fictitious identities, five individuals who completed forms, and three who checked forms. Also, we initially considered only four patterns and variations in them. CONCLUSIONS: We defined a masking pattern that satisfactorily fulfilled our needs for confidentiality. This and other procedures for remote preenrollment checking of consent form can be a key component of a risk-based monitoring strategy.

Ensuring quality control in a COVID-19 clinical trial during the pandemic: The experience of the Inserm C20-15 DisCoVeRy study.

SETTING: Health measures taken during the pandemic deeply modified the clinical research practices. At the same time, the demand for the results of the COVID-19 trials was urgent. Thus, the objective of this article is to share Inserm's experience in ensuring quality control in clinical trials in this challenging context. OBJECTIVES: DisCoVeRy is a phase III randomized study that aimed at evaluating the safety and efficacy of 4 therapeutic strategies in hospitalized COVID-19 adult patients. Between March, 22nd 2020 and January, 20th 2021, 1309 patients were included. In order to guarantee the best quality of data, the Sponsor had to adapt to the current sanitary measures and to their impact on clinical research activity, notably by adapting Monitoring Plan objectives, involving the research departments of the participating hospitals and a network of clinical research assistants (CRAs). RESULTS: Overall, 97 CRAs were involved and performed 909 monitoring visits. The monitoring of 100% of critical data for all patients included in the analysis was achieved, and despite of the pandemic context, a conform consent was recovered for more than 99% of patients. Results of the study were published in May and September 2021. DISCUSSION/CONCLUSION: The main monitoring objective was met thanks to the mobilization of considerable personnel resources, within a very tight time frame and external hurdles. There is a need for further reflection to adapt the lessons learned from this experience to the context of routine practice and to improve the response of French academic research during a future epidemic.

"Reading the Mind in the Eyes" in Autistic Adults is Modulated by Valence and Difficulty: An InFoR Study.

Autism spectrum disorders (ASD) are heterogeneous and complex neurodevelopmental conditions that urgently need reliable and sensitive measures to inform diagnosis properly. The Reading the Mind in the Eyes Task (or Eyes Test from now on) is widely used for this purpose. A recent study showed that subcategories of items of the children version of the Eyes Test could be especially discriminative to distinguish ASD and control children. Here, we analyzed the performance on the Eyes Test of 30 high functioning (IQ > 70) adults with ASD and 29 controls from the InFoR cohort multicentric study, using a Generalized Linear Mixed Model. We found that valence and difficulty modulate the performance on the Eyes Test, with easy and positive items being the most discriminative to distinguish ASD and controls. In particular, we suggest this result might be actionable to discriminate ASD patients from controls in subgroups where their overall scores show less difference with controls. We propose for future research the computation of two additional indexes when using the Eyes Test: the first focusing on the easy and positive items (applying a threshold of 70% of correct responses for these items, above which people are at very low risk of having ASD) and the second focusing on the performance gain from difficult to easy items (with a progression of less than 15% showing high risk of having ASD). Our findings open the possibility for a major change in how the Eyes Test is used to inform diagnosis in ASD. LAY SUMMARY: The Eyes Test is used worldwide to inform autism spectrum disorders (ASD) diagnosis. We show here that ASD and neurotypical adults show the most difference in performance on subgroups of items: ASD adults do not improve as expected when comparing easy and difficult items, and they do not show an improvement for items displaying a positive feeling. We advise clinicians to focus on these comparisons to increase the property of the test to distinguish people with ASD from neurotypical adults.