How To Suspend At&t Service For A Month
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How to deal with a temporary interruption and restarting your trial: our experiences and lessons learnt
Trials volume 21, Article number:765 (2020) Cite this commodity
Abstract
Whilst the issues around early termination of randomised controlled trials (RCTs) are well documented in the literature, trials can too be temporarily suspended with the real prospect that they may afterwards restart. There is little guidance in the literature as to how to manage such a temporary suspension. In this paper, we describe the temporary suspension of a trial within our clinical trials unit because of concerns over the safety of transvaginal synthetic mesh implants. We too describe the challenges, considerations, and lessons learnt during the pause that we are now applying in the current COVID-xix pandemic which has led to activities in many RCTs across the globe undergoing a temporary break.
At that place were three key phases within the temporary intermission: the decision to suspend, implementation of the suspension, and restarting. Each of these phases presented individual challenges which are discussed within this paper, along with the lessons learnt. There were obvious challenges around recruitment, delivery of the intervention, and follow-up. Additional challenges included communication between stakeholders, evolving risk cess, updates to trial protocol and associated paperwork, maintaining site engagement, data-analysis, and workload within the trial squad and Sponsor arrangement.
Based on our experience of managing a temporary intermission, nosotros developed an activeness plan and guidance (come across Additional File i) for managing a significant trial consequence, such every bit a temporary break. We have used this document to help us manage the suspension of activities within our portfolio of trials during the current COVID-19 pandemic.
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Background and introduction
The early on termination of randomised controlled trials (RCTs) for planned reasons such as statistically based stopping rules, loss of funding, poor recruitment, or futility is well documented [1,2,3,four,5,6]. However, trials can also be temporarily suspended or put 'on concord' rather than terminated, with the existent prospect they may afterwards restart.
Several factors can trigger such a interruption: the most common being effectually a rubber concern, or a perceived shift in the risk/benefit residue (or other ethical concerns) [7]. Internal study factors may also play a role, such equally the chief investigator or master investigator being temporarily unavailable, or poor data quality identified during monitoring exercises. External factors may include drug supply bug, trial equipment problems, monitoring inspection findings, or new evidence from other studies. More recently, the global COVID-xix pandemic has likewise resulted in the temporary intermission of many clinical studies [8].
A search of the literature revealed very picayune guidance on how to manage a temporary suspension. We are aware of some accounts through 'word of mouth' from other trialists. In this paper, nosotros aim to document the experiences and lessons learnt within our Britain Clinical Research Collaboration (UKCRC) Clinical Trials Unit (www.ukcrc-ctu.org.uk) (CTU; Heart for Healthcare Randomised Trials (Nautical chart), Health Services Research Unit of measurement, University of Aberdeen) of a temporary trial suspension.
Our experience
A publicly funded (UK NIHR Health Engineering Assessment Programme) surgical RCT, VUE [ix, 10] (Vault or Uterine prolapse surgery Evaluation (ISRCTN86784244)), was temporarily suspended in 2014 in Scottish sites just due to general concerns external to the trial on the safety of transvaginal (TV) synthetic mesh implants.
The trial intermission was triggered when the Scottish Regime (June 2014) asked all Scottish NHS Health Boards to consider suspending the use of TV synthetic mesh implants (http://www.parliament.scot/parliamentarybusiness/study.aspx?r=9275&mode=pdf [11]). This was to enable an independent review to consider the ongoing debate on complexity rates and underreporting of agin incidents in the treatment of stress urinary incontinence (SUI) and pelvic organ prolapse (POP) using TV synthetic mesh implants.
VUE incorporates ii parallel RCTs evaluating the surgical options for either uterine or vault prolapse which involved or potentially involved the utilize of Goggle box synthetic mesh implants as part of the surgical intervention (Table 1). In VUE, mesh use was largely dependent on the surgeon'due south routine practice, and non specified by the trial. Of note is that the Scottish Government requested suspension was specifically related to the Television set utilise of constructed mesh; the intestinal use was not included in this suspension.
VUE was actively recruiting participants and had total approval from an NHS Enquiry Ideals Committee (REC) when the temporary trial suspension occurred. At the time of the suspension in 2014, there was no new emerging bear witness within scientific journals or medical literature nor updates or changes to the UK NICE clinical guidelines (IPG215, IPG283, IPG282, IPG284 (no longer available online)).
Decision to append
The Scottish Government'south request to consider suspending the employ of Tv set synthetic mesh in incontinence and POP surgery in Scotland was initially widely interpreted as 'a ban' (https://www.independent.co.uk/news/uk/abode-news/vaginal-transvaginal-tvt-sling-the-mesh-scandal-nice-guidelines-health-watchdog-nhs-sui-incontinence-a8111721.html [12]), causing confusion non only for the Scottish NHS Wellness Boards and clinicians but besides for patients, trial participants, and our CTU. The trial Sponsor therefore immediately suspended the activity, as described below, in Scottish NHS Health Boards until farther information could be reviewed and assessed. The Sponsor and Funder requested urgent data on how the Scottish Government'due south request to suspend the employ of Idiot box mesh would impact the trial. Trial activity in the residue of the UK did non modify as no similar activeness/asking was taken by the U.k. Regime.
Implementation of the suspension
The temporary pause involved three Scottish trial sites and incorporated suspending recruitment of any new potential participants, as well equally suspending randomisation of eligible participants who had already consented to take office. The randomisation line was airtight for the Scottish sites, and for trial participants near to receive surgery (the trial intervention), we advised the local clinical team (principal investigator and research nurses) and local R&Ds to attach to their local NHS governance decision on the use of Television receiver synthetic mesh (some NHS Scotland Boards did suspend the employ of TV mesh, whilst others did not).
The trial team ensured that the key stakeholders (Funder, REC, trial oversight groups: Projection management Group (PMG), Trial Steering Committee (TSC), and independent Data Monitoring Committee (iDMC)) together with the local clinical team were notified and kept upwardly to appointment throughout the suspension period. Emergency trial oversight commission meetings of the iDMC and TSC were organised to discuss the impact or potential bear upon on the trial, and the ongoing demand for robust bear witness. The Sponsor likewise revised their risk assessment.
Information technology is worth noting that the suspension occurred over a relatively brusk period of fourth dimension (3 weeks in total) from the initial Scottish Government request (to Scottish Health Boards) to the lifting of the pause.
Restarting
Sponsor made the decision to lift the suspension and restart trial activity in Scotland one time they were satisfied that all recommendations, questions, or concerns from the key stakeholders had been met. The Sponsor as well confirmed their clinical trials insurance connected to cover activity within the trial.
The Scottish sites were made aware of the outcome of the suspension. For these sites, this also involved the need to explain that the lifting of the temporary suspension related only to the research (i.e. the VUE Trial) and non to the Scottish Government's request to suspend the use of Tv set synthetic mesh in all SUI and POP surgeries (the Scottish Government had clarified that the utilize of Tv set synthetic mesh could continue in clinical trials). This meant that within VUE, the Scottish sites could perform POP surgery using Television synthetic mesh, provided fully informed consent was obtained.
Finally, the randomisation line was reopened on 3 July 2014 for those Scottish sites impacted by the temporary suspension, and the key stakeholders informed that the intermission had been lifted.
Challenges, considerations, and lessons learnt
An effect that triggers a temporary pause tin happen at whatsoever stage of the trial (e.g. set up-up, recruitment, treatment, or follow-up). Therefore, consideration needs to be given as to who and what is affected past a pause; be it screening and recruitment (or even contracting and financial contacts in the set-up phase); randomisation; delivery of the intervention or the length, type, or frequency of participant follow-up; scheduled meeting of study oversight committees (TSC and iDMC); progress reports to the funder; and also scheduled monitoring and site visits for quality assurance purposes. Indeed, pretty much any of these trial activities, that establish a multicentre pragmatic trial, can be adversely influenced by a suspension.
We identified a number of key challenges associated with managing a temporary interruption of unknown duration. These challenges, together with considerations and insights as to how these may be overcome, are described below:
Planning
The first task identified in managing an event such as a trial intermission is to establish a task forcefulness and nominate a 'Significant Event Lead'. In addition to the Lead, the cardinal team members of the task strength included the chief investigator, trial manager, quality assurance director, and CTU manager. Identifying the cardinal stakeholders and creation of distribution lists was too important, as well every bit prioritising who would crave initial contact and standardising the communication outputs.
As this was our first experience of a temporary suspension, we had no formal process to guide us. We therefore created a 'guidance for significant major events' document (including delegation of specific actions) too equally an 'events and deportment timeline' template (Additional File one) during this catamenia, which was specially challenging due to the fast-paced nature of the event.
Our guidance detailed the requirements and actions to consider if suspending randomisation, communication/notification of all stakeholders, and the process for responding to press and Liberty of Data (FOI) queries (i.e. who is responsible and who is deputy if that individual is not available). The 'events and actions timeline' evolved in real time merely was also updated and renewed over time to ensure it was an accurate reflection of what happened, and when.
We highly recommend documenting all the information related to a 'major event' (the temporary suspension) in such an 'events and action timeline', which could include whatever immediate corrective/preventive action, and ascertain responsibilities. This timeline document can then evolve over the lifetime of the upshot and exist updated accordingly.
Bringing the task force together following such an result is extremely of import to ensure consistency and accuracy in documenting the lessons learnt, too as updating or making changes to processes (if required) or to ensure preparation for any future similar events.
Maintaining an authentic record of all events is extremely of import. We fix a defended (and secure) folder to provide a suitable facility for the memory of all relevant documents that staff involved could access. These records could exist held electronically, as hardcopy or as a hybrid organisation. A hard copy or screenshot of any relevant spider web articles should exist retained as these may subsequently become unavailable online over time.
Communication
Timely, consistent, and authentic communication is key, both within the trial squad and to stakeholders. This can be particularly important (as was the case for us) given the potential speed of development of ongoing events and decisions, to ensure everyone could confidently rely on the information given out by the trial part as existence correct and authoritative.
The advice needs of all stakeholders had to be met. The stakeholders included the Sponsor, Insurer, Funder, REC, oversight committees, sites, clinical staff, and participants. Careful consideration of what should be shared was necessary. Updates needed to be consistent, and the amount and complexity of item varied depending on the stakeholder in order non to overwhelm them with besides much detail (e.g. what is communicated to trial participants compared to the Sponsor). These communications were coordinated past the 'Meaning Event Lead'.
The way of advice also required consideration. We used a variety of communication methods to convey the necessary data to all stakeholders such as e-mail, telephone, and meetings likewise as apply of the site specific (not-public) trial websites (where logins/access could be monitored to verify access to the changing information).
Differing interpretations of the Scottish Government's request to suspend the use of Tv synthetic mesh, also as media reporting of the event, were specially challenging, equally many Scottish Health Boards interpreted the request differently. For instance, it was unclear from the initial report if it was only for incontinence or Pop or if information technology was specifically related to the TV utilize of mesh in any process.
In add-on, nosotros realised different stakeholders also had dissimilar interpretations of what a temporary intermission really meant (for example: patients could not be screened; patients could non be recruited; the intervention could not go alee; in that location could be no clinics or follow-upwards), and risk aversion varied among these stakeholders.
In society to communicate clearly, nosotros needed to analyze (to ourselves and ultimately to the sites) what a temporary suspension actually meant; in this instance, no recruitment or randomisations could go alee. We prioritised closing the randomisation line ahead of informing sites.
The initial steps in restarting the trial, after lifting the interruption, were primarily to ensure the various stakeholders were happy to proceed their interest. The Sponsor, iDMC, TSC, and Funder needed to be kept fully informed throughout, specially with any potential bear on on the written report processes. Understanding from all stakeholders was necessary earlier the decision to elevator the temporary suspension was made.
The media and patient groups can also generate FOI requests (Table 2) to the trial function, Sponsor, REC, Funder, and sites. As a result, the trial office needs to be vigilant to such requests and ensure they are managed and handled according to the Institution'due south policy. This ensures such requests are handled by those with the relevant feel and understanding and provided consistency in responses. This can be particularly helpful if the aforementioned requests are sent to multiple stakeholders, including the trial part, Sponsor, REC, and Funder.
Risk assessment
The risk assessment of the trial may demand to be reviewed to consider if any changes are required, for case, updates to the safety reporting processes. Uncertainty around the suspension may also issue in the hazard being reclassified by the Sponsor, potentially involving increased reporting or monitoring requirements.
Our trial underwent an updated risk assessment and was also reclassified by our Sponsor from a moderate to a loftier take chances trial, resulting in increased monitoring and revision of serious adverse event reporting to that in line with drug trials.
Updates to trial protocol/paperwork
The trial protocol or paperwork may likewise demand revised/amended depending on the reason for a temporary break. To make this process as smooth as possible, we recommend any changes to the study protocol or paperwork involve the key stakeholders to ensure everyone has an opportunity to discuss and agree to any required changes.
Site appointment
The reason(s) and length of a suspension are probable to influence site engagement. For example, if the pause is due to condom concerns, this could atomic number 82 to a bigger bear upon than say drug supply bug.
Our feel taught us that some sites were happy to reopen and recommence all trial activities whilst others were more than reserved. Some sites will reopen but not continue to recruit participants due to reticence on the part of the principal investigator (PI)/surgeon and/or the hospital clinical director. Others will open but remain inactive and not recruit whatever further participants due to a turn down in potential and/or willing participants, or sites may remain closed whilst waiting for farther guidance/updates, etc.
A temporary trial break may likewise bear on potential new sites and sites in set upwardly. Potential sites may then decline to take part in the trial or delay their participation indefinitely.
To maintain engagement of site staff, we prioritised other trial-related activities during the suspension, such equally information checks, ongoing training, and regular communication.
Engaging the local research networks to ensure site staff are not moved on to other projects may besides be important in retaining the sites' engagement.
Further training for site staff or trial marketing should exist considered if relevant, depending on the reason and length of suspension.
Recruitment and randomisation
A temporary trial suspension may impact recruitment of trial participants. It may be that some sites recruit more than slowly equally they either no longer prioritise the trial locally or continue to have ongoing concerns post-obit the suspension.
One time the suspension was lifted, recruitment was closely monitored to establish if it had slowed down. The impact of the suspension and reopening of the trial varied beyond the three sites; this was related to site and team engagement (as described above). The impact on recruitment on our trial was difficult to evaluate.
The randomisation system we utilise was designed such that randomisation could be stopped immediately in individual or all sites. When the suspension was lifted, the randomisation line was reopened, and we recommend it is re-tested to ensure there are no problems. In that location may also be an opportunity to add together central information to the randomisation system alerting sites to the suspension, particularly if it is an international trial and time zones brand it difficult to communicate with individual sites in a timely mode.
Delivery of the intervention
For our suspension, we deferred to the local NHS policy for handling using TV synthetic mesh implants. During this intermission, that meant no participants received their randomised surgical procedure until after the interruption was lifted. Considerations for the commitment of the trial intervention are essential. In non-surgical studies, decisions around the ongoing delivery of the intervention may be more complex—for instance, if trial participants are taking written report drugs in the customs.
Follow-upwardly
Retentivity and follow-upwardly of trial participants may also be impacted. Depending on the affliction area/trial intervention, one bear upon of a break may exist that more frequent participant follow-up is implemented. An increase or subtract on participant questionnaire response rates may likewise be experienced as heightened awareness may influence whether participants cull to engage. Again, this was difficult to evaluate in our trial.
Information and analysis
The temporary break may take an affect on trial information (amount being nerveless/integrity/changes prior to the suspension). Consideration should be made to how this will exist handled in the information analysis. Differences may be observed in baseline characteristics pre- and postal service-break, and/or at that place may be an event on the outcome information. It may exist advisable to do sensitivity analyses to evaluate the data before and after the pause to reassure the findings are robust. If this is done, it is also important to update the statistics analysis plan (SAP).
Workload
Not surprisingly, the affect on the trial role will likely involve an increase in workload, maybe resulting in a shift in the types of tasks that require to be undertaken, along with the usual twenty-four hour period-to-day work.
This increased workload may stem from addressing participant queries, Sponsor concerns, and changes to study documentation/paperwork and addressing concerns and queries from sites, key stakeholders, and media (through FOI requests, Tabular array 2). In addition, sites may require reassurance that the study will continue and confirmation of new study processes. Some sites may also crave extra back up to deal with the increase in participant queries.
An unanticipated impact on the trial office workload came from the media and patient groups. This was in the form of increased queries and the need to exist more vigilant and consistent in our response.
Conclusion
Whilst a trial suspension may be brusque in duration, the bear on on the study should not be underestimated. VUE was temporarily suspended for a relatively short period, but the bear on continues. Given the contempo COVID-19 pandemic, nigh trials volition be experiencing a suspension of some or all of their activities.
In this newspaper, we have described our experiences of a temporary trial suspension and highlighted the demand for farther guidance of such a pregnant trial event. In order to provide some guidance for other trialists who may experience a temporary suspension of their trial, we have detailed the cardinal challenges we experienced, together with insights every bit to how these may be overcome.
Given our previous experience of a temporary suspension, we were well placed to deal with the suspension of trial activity as a result of the electric current COVID-19 pandemic. Within our own Unit, 17 trials had recruitment and/or follow-upwardly suspended, or aspects of their intervention delivery or follow-upward altered, to conform the impact of COVID-19. All these trials successfully used the guidance adult for pregnant major events and populated the events and actions timeline template (Boosted file 1). The actions timeline continues to be helpful for reporting to Funder, Sponsor, REC, oversight committees, participants, sites, clinical staff, and within our firsthand trial teams. It is also likely to prove helpful when reporting trial results in the future.
As a Unit, nosotros accept developed and tested our pregnant major events and timeline documents in ii very dissimilar scenarios and plan to continue to apply them for any future events.
Availability of data and materials
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Funding
VUE is funded by the National Institute for Health Research (NIHR) Wellness Applied science Assessment (HTA) programme (projection reference 11/129/183). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
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LC conceived the idea for the manuscript. All authors contributed to the writing, analysis, and reviewing of the manuscript and agreed to its publication. All authors read and approved the final manuscript.
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Lawman, L., Davidson, T., Breeman, South. et al. How to deal with a temporary pause and restarting your trial: our experiences and lessons learnt. Trials 21, 765 (2020). https://doi.org/10.1186/s13063-020-04705-iv
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DOI : https://doi.org/10.1186/s13063-020-04705-4
Keywords
- Temporary suspension
- Suspend
- Randomised controlled trial
- RCT
- COVID-19
Source: https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-020-04705-4
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