Methods
All trials which had worked with the QuinteT researchers to optimise recruitment and informed consent were considered for inclusion (
n = 14). Six trials considered in previous development work to map the recruitment pathway were excluded [
4,
5,
10]. Eight trials anticipating or experiencing recruitment difficulties were included using a convenience sampling approach. The eight RCTs were managed by seven different clinical trials units (CTUs); three were feasibility studies, two pilot studies and three main trials. Ethical approval for the QRI research, including the use of screening log data, was obtained within the governance arrangement for each RCT.
We use the term ‘screening’ or ‘recruitment’ log to refer to an “essential document that records all individuals who entered pre-screening or screening, and details the reasons why an individual is not enrolled ” [
11]. Following this definition, we focused on two functions of a screening log:
1.
to record key characteristics of all individuals considered for trial participation
2.
to capture the reasons why an individual was not enrolled in a trial
We conducted a directed content analysis [
12] of the screening logs used in the eight trials, to identify which aspects of the recruitment pathway and process were assessed and which were useful to monitor recruitment. We reviewed all trial documentation [protocol, manual, case report forms (CRFs), screening logs] and extracted all references to recruitment, screening, screening log, eligibility checks, information provision, and randomisation. Data were analysed thematically and synthesised using the constant comparative method, adapted from grounded theory [
13,
14].
As part of the thematic analysis, codes were developed to summarise the information included in each screening log. The codes were used to identify the recruitment stages. The thematic analysis was conducted independently by the first author (CW) and the trial-specific QuinteT researcher (DE, MJ, SP, LR, and SS). The codes were presented to the wider group (DE, MJ, SP, LR, SS, CW, and JD) to develop a consensus about the key stages in the recruitment process that could be captured by a log. The stages (screening, eligibility assessment, approaching, and recruited/randomised) were then used to conduct a directed content analysis to identify how each trial recorded this information. The findings from the content analysis were further synthesised by CW to produce the SEAR framework. The recommendations presented in the article were developed by CW and JD, and are a synthesis of the findings from this study, combined with experience from other QRIs in RCTs addressing recruitment problems.
Discussion
CONSORT guidelines emphasise the importance of recording some basic aspects of screening and eligibility assessment before randomisation, but there has been little consensus over how much data to collect or how best to do this. We compared the content of screening/recruitment logs in eight comparatively small hospital-based RCTs with an integrated QRI which encouraged the keeping of such logs. This content was synthesised to develop a simple framework that could be used or adapted to suit most RCTs, particularly those with recruitment difficulties and multiple clinical centres. The SEAR (Screened, Eligible, Approached, Randomised) framework supports the collection of information that can be used to identify recruitment obstacles which can then be addressed in order to improve the recruitment process.
With so many trials failing to enrol sufficient numbers, recruitment challenges have been well documented – lower than expected numbers of referrals or eligible patients, organisational issues at recruiting centres, problems with the trial design, complex clinical or recruitment pathways, and lack of clinician and patient equipoise [
5,
15‐
18]. Some of these problems could be identified through the collection and analysis of screening data, but few trials collect or publish information about participants before randomisation, beyond the numbers necessary to meet CONSORT guidelines [
3,
10]. The SEAR framework augments CONSORT guidelines, and, building on the findings of QRIs, recommends the recording of the number of potential participants excluded because they were not approached, and the reasons why potential participants were excluded from the trial (i.e. reason for ineligibility, non-approach, declined), as well as the final treatment received by eligible patients.
Logging the progress of potential participants through eligibility checks to final decision about trial participation and treatment is relevant to all clinical trials. However methodological interest in screening data has been somewhat limited to emergency medicine trials in relation to concerns about selection bias and the generalisability of trial results [
19,
20], in population-based cancer screening studies to increase clinical trial participation [
21,
22] and less frequently as a tool to monitor trial eligibility and recruitment rates [
23].
The SEAR framework defines four key stages in the recruitment process where participants may be lost, and provides recommendations for data collection. The SEAR framework requires trial-specific adaptations and instructions to harmonise recruitment practices in multicentre trials and optimise the use of resources to identify trial-specific recruitment problems. Unnecessary screening can be minimised through trial-specific criteria for entry into the SEAR process. In practice, the distinction between Screening (initial identification and entry into the SEAR log) and Eligibility assessments (against essential trial inclusion and exclusion criteria), may be blurred in some trials. Time and effort may be wasted screening large numbers of participants who turn out to be ineligible. Other RCTs or clinical centres may take a minimalistic approach to screening, so that only participants deemed highly likely to be eligible are approached to join the trial and entered onto the screening or recruitment log. In trials with small numbers of eligible patients, it may be beneficial to conduct eligibility checks on a larger number of patients to understand key reasons for ineligibility. Although the final outcome of eligibility checks may not be confirmed before patients are approached for trial participation, the SEAR log has been designed to capture information over time (eligibility pending, or awaiting patient decision) and flexibly, according to trial-specific recruitment priorities and concerns.
Least attention has been devoted to define when and how to approach potential participants, although this is where many are often lost [
5,
15]. To optimise the number of potential participants approached to join an RCT, we recommend logging the date written information is provided, when the trial is discussed, and when a participant is invited to join the trial. Regarding eligibility, we also recommend data about key eligibility criteria are recorded so that it is possible to identify local decision-making, and final treatment selected or received by non-randomised eligible patients.
Doubts about the scientific value of screening data have led some to argue that the effort to collect high-quality screening data outweighs any benefit [
24]. In particular, concerns have been raised about the lack of standardised criteria for
screened participants and differences in site processes that make the collection of uniform data problematic in multicentre trials. The collection of screening data can be difficult and time-consuming, and may not be needed in detail for all trials, but qualitative research in QRIs has indicated its value. Suboptimal screening can limit the number of potentially eligible patients given the opportunity to enrol in an RCT [
25]. Recruiters often struggle to reconcile the desire to gather robust evidence with their clinical instincts and concerns about patient eligibility and safety [
5].
Screening data collected by the CTU has been analysed by QRI researchers to help identify these clear obstacles and more subtle hidden challenges so that they can be addressed [
15] – for example identifying lower than anticipated numbers of eligible patients and differences between clinical centres in eligibility assessment [
10,
26,
27]. Previous research has shown trialists sometimes experience discomfort offering the RCT to all patients, even though the patient technically meets all the trial inclusion and exclusion criteria [
5,
15]. Identifying differences in the interpretation of eligibility criteria can be useful to target training and support to improve clinician equipoise [
5,
15,
28]. Screening data were also discussed in feedback sessions to address hidden challenges [
15,
25], and analysis of final treatment received informed feedback and training sessions to improve equipoise in another trial [
26].
There are further examples of the usefulness of log data in the eight RCTs included here. In T1, screening data helped to ensure potential trial participants were identified, logged and provided with information about the trial early in the pathway. Screening practices were particularly important because the condition was rare, and coordination was required across two specialties. Data were also used to identify high volume centres, so that additional training and support could be targeted to improve the recruitment rate in centres screening the most potentially eligible participants. Given greater interest in embedded recruitment studies [
29,
30], screening data can provide important information to evaluate the effectiveness of recruitment interventions.
The Screened, Eligible, Approached, Randomised (SEAR) framework supports the collection of data as a tool to map the recruitment process and identify barriers to recruitment. It can be particularly helpful in pilot or feasibility studies, to assess feasibility and inform recruitment strategies for a main trial. Data for the SEAR log can be collected according to the preferred method of the CTU and/ or clinical centres, in the centre log format, using a CRF-style form, or an as app or iPad with supporting database. The SEAR framework and log have been designed so they can be adapted to monitor recruitment in any RCT, but is likely to add most value in trials where recruitment problems are anticipated or evident, and in multicentre trials.
There are some limitations to this study and the framework. The trials included in this study had integrated QRIs, and so there was already a heightened awareness of recruitment issues. The sample size, although small, did include main trials, feasibility, and pilot studies. However, we did not find notable difference between different types of studies. Three out of five pilot/feasibility studies have progressed to a main trial, and are currently using a similar screening log to map the recruitment pathway in the main trial with an integrated QRI. Other trials may find it more difficult to collect such data and it is recommended that the resources needed to support the collection and management of SEAR data are adequately costed for in the grant proposal.
The RCTs sampled here were all National Health Service (NHS) hospital-based studies, evaluating treatments for non-emergency procedures for cancer or chronic conditions. The total number of patients screened for each trial was comparatively small. Much larger trials or trials identifying patients from primary care may need to conduct basic eligibility checks before entering patients into the SEAR process, to streamline the SEAR framework, or may not need it in full. The SEAR process can be time-consuming and requires resources from recruiting centres which may be a problem for some RCTs and CTUs. However, the investment may reveal information about recruitment difficulties that remain such a source of difficulty for many RCTs. The framework could be a useful tool in emergency medicine trials, where it is important to closely monitor the appropriateness and application of eligibility criteria [
19,
20].
The SEAR framework and logs included in this study collected information exceeding the CONSORT reporting guidelines, and National Institutes of Health (NIH) (2014) definition of a screening log [
11]. However, the CONSORT guidelines conflate screening criteria with eligibility criteria, and eligibility criteria with those approached for study participation. Previous syntheses of qualitative research [
4,
5] and findings from the content analysis here show that the recruitment pathway in most trials follows the SEAR stages: Screening, Eligibility, Approached, Randomised. As such, the SEAR framework could be used to update CONSORT reporting guidelines, following further work to test and validate this approach in other types of trials, with different groups of investigators and outside the NHS context. Although CONSORT was extended to improve pilot and feasibility study reporting, the guidelines did not substantially revise data on screening except for reporting numbers approached [
31].
Acknowledgements
Collaborating members of the RCT study groups are shown below:
ACST-2 study group (ISRCTN 21144362): Alison Halliday, Richard Peto, Richard Bulbulia, Hongchao Pan, Leo Bonati, John Potter, Alastair Gray, Borislava Mihaylova, Peter Rothwell, Sumaira MacDonald, William Gray, Han-Henning Eckstein, Barbara Farrell, Christina Davies, David Simpson, Piergiorgio Cao, Michael Gough, Anna Belli, Jenny L. Donovan, Dafydd Thomas, Averil Mansfield, Kazim Rahimi, Marcus Flather, Alison Clarke, Mary Sneade, Kasia Slopien, Wojciech Brudlo, Johanna Chester, Lynda Tully, Michael Lay, Sergey Tochlin, Andrew Munday, Clive Berry, Alan Young, Marion Mafham, Will Herrington, Peter Sandercock, Richard Gray, Cliff Shearman, Andrew Molyneux.
By-Band-Sleeve study group (ISRCTN 00786323): Chris A. Rogers, Robert Andrews, Jane M. Blazeby (chief investigator), James Byrne, Jenny L. Donovan, Jamie Kelly, Graziella Mazza, David Mahon, Hamish Noble, Barnaby C. Reeves, Janice L. Thompson, Sarah Wordsworth, Richard Welbourn.
Chemorad study group (ISRCTN 89052791): Jane M. Blazeby (chief investigator), Paul Barham, Sara T. Brookes, Tom Crosby, Jenny L. Donovan, Stephen J. Falk, S. Michael Griffin, William Hollingworth, Andrew D. Hollowood, Richard Krysztopik, Wyn Lewis, Jo Nicklin, Christopher Streets, Sean Strong, Dan Titcomb, Geraint Williams.
CSAW study group (ISRCTN 33864128): David J. Beard (co-chief investigator), Andrew Carr (co-chief investigator), Jonathan Cook, Cushla Cooper, Benjamin Dean, Jenny L. Donovan, Alastair Gray, Stephen Gwilym, Andrew Judge, Naomi Merritt, Jane Moser, Jonathan Rees, Ines Rombach, Julian Savulescu, Irene Tracey, Karolina Wartolowska.
OPTIMA prelim study group (ISRCTN 42400492): Rob C. Stein (chief investigator), John Bartlett, David Cameron, Amy Campbell, Peter Canney, Jenny L. Donovan, Janet Dunn, Helena Earl, Mary Falzon, Adele Francis, Peter Hall, Victoria Harmer, Helen Higgins, Luke Hughes-Davies, Claire Hulme, Iain Macpherson, Andreas Makris, Andrea Marshall, Christopher McCabe, Adrienne Morgan, Sarah Pinder, Christopher Poole, Daniel Rea, Nigel Stallard.
PART study group (ISRCTN 99760303): Freddie C. Hamdy (chief investigator), TA Leslie, SF Brewster, Jenny L. Donovan, D. Elliott, J Wolstenholme, R Gray, C Verrill, FV Gleeson, R McPherson, P Sooriakumaran, D Beesley, D Gillatt, J Catto, D Rosario HY Ahmed, M Emberton, P Cathcart, R Persad, Steffi le Conte.
POUT study group (ISRCTN 98387754): Alison Birtle (chief investigator), Rik Bryan, James Catto, John Chester, Jenny L. Donovan, Ann French, Emma Hall, Chris Harris, Mark Johnson, Rob Jones, Francis Keeley, Emma Jones, Tony Kirkbank, Roger Kockelbergh, Rebecca Lewis, Lauren Maynard, Michelle Newton, Thomas Powles, Arumugam Rajesh, Rachel Waters, Caroline Wilson, Andrew Winterbottom.
ROMIO study group: (ISRCTN 59036820) Kerry Avery, Chris Metcalfe (chief investigator), Jane M. Blazeby, Richard Berrisford, C. Paul Barham, Jenny L. Donovan, Jackie Elliott, Stephen J. Falk, Rob Goldin, George Hanna, Andrew A. Hollowood, Richard Krysztopik, Sian Noble, Grant Sanders, Christopher G. Streets, Dan R Titcomb, Tim Wheatley
The authors also acknowledge the valuable support of the following members of the QuinteT team in this work: Kerry Avery, Carmel Conefrey, Samantha Husbands, Nicola Mills, Julia Wade, and Paul Whybrow.