IRB challenges in multisite studies: A case report and commentary from the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA)

Specific challenges and impacts of ethics processes for multi-site studies

Applications for approval to multiple IRBs increase the complexity of the ethical review process and add to the bureaucracy associated with obtaining approval (Driscoll et al., 2008; Marquis-Gravel et al., 2021; Samir et al., 2022; Smith et al., 2019). Increased complexity may further impact the process by making communication more challenging for researchers (Smith et al., 2019). Rather than being supportive, the increased complexity of the ethics process may actually be a barrier to conducting ethical research (Samir et al., 2022).

Another challenge associated with application processes involving multiple IRBs is the time taken to obtain full approval. While multi-site studies may speed up the recruitment process, one of the critical challenges of multiple IRB ethical approval is the impact that the prolonged process may have on project timeframes, with particular implications for initiating the research process (Driscoll et al., 2008; Gold & Dewa, 2005; Greene & Geiger, 2006; Marquis-Gravel et al., 2021; Racine & Bracken-Roche, 2019; Salt, 2019; Samir et al., 2022; Smith et al., 2019). The impact for one national study was estimated at a six-eight month delay in the research (Driscoll et al., 2008), while others were concerned that delays in the process led to a loss of faith in research amongst communities (Brown et al., 2008). Another practical challenge associated with multiple IRB applications is the direct impact they have on project costs and resource implications related to applying to multiple different individual institutions (Gold & Dewa, 2005; Greene & Geiger, 2006; Salt, 2019; Smith et al., 2019).

Another critical challenge highlighted in the literature, with a number of different possible implications, relates to the variability and inconsistency involved in ethical review processes across different IRBs (Driscoll et al., 2008; Gold & Dewa, 2005; Marquis-Gravel et al., 2021; Salt, 2019). This may stem in the first place from inconsistent ethical requirements between different institutions (Driscoll et al., 2008). Inconsistency may arise as different IRBs may have different models in place or interpret guidelines differently (Salt, 2019), which may be related to an absence of standardised forms, varying backgrounds and experiences of IRB members, and varying interpretations due to different culture and thinking at a cultural or regional level (Gold & Dewa, 2005). Inconsistency may also relate to different views on methodological approaches (Salt, 2019). Of particular relevance to intellectual disability research, Salt (2019) noted that inconsistency between IRBs may arise with regard to research with vulnerable populations, with different interpretations of vulnerability, ability to consent, and levels of risk.

However, as noted above, such challenges in the practical implementation of multi-site studies may remain even where policy and guidance provide for a single, centralised system, meaning that this type of research may still be “complex, bureaucratic and time consuming” (Samir et al., 2022: 16).

Strategies for navigating the ethics process for multi-site studies

Several strategies have been identified in the literature to help researchers to overcome or mitigate the challenges that are presented in guiding multi-site studies through the ethical review process, especially where multiple IRBs are involved. Early advanced planning is important in anticipating and meeting issues that may arise during the application process (Nichols et al., 2019; Salt, 2019; Samir et al., 2022). Proactive engagement with IRBs, representatives and key personnel may also help to identify and mitigate issues and concerns, as well as build better understandings of the proposed project in advance of formal applications (Marquis-Gravel et al., 2021; Salt, 2019; Samir et al., 2022). Related to both planning and proactive engagement, good clear communication and the development of a communication plan were identified as important to facilitating a smoother application process (Marquis-Gravel et al., 2021; Nichols et al., 2019). Also stemming from these strategies is the recommendation to develop good working relationships with local actors (Marquis-Gravel et al., 2021; Nichols et al., 2019), providing education and training for all parties to better inform and prepare everyone about the study and related regulatory expectations (Gold & Dewa, 2005; Nichols et al., 2019), and to advocate for the study and its population (Salt, 2019).

Above all, the development of a single, centralised and coordinated IRB system underpinned by an agreed framework at national or regional level is recommended as a strategy to overcome many of the challenges inherent in multiple IRB systems (Cobb et al., 2019; Driscoll et al., 2008; Gold & Dewa, 2005; Samir et al., 2022). This may involve a common application form and documentation (Driscoll et al., 2008; Gold & Dewa, 2005) and a shared electronic platform for easier management of information (Cobb et al., 2019; Gold & Dewa, 2005; Samir et al., 2022). Such strategies may create a streamlined and integrated review process nationally and a mechanism to coordinate requests for more information (Samir et al., 2022) with a process of full ethical review by a primary IRB and subsequent expedited review by other IRBs involved (Driscoll et al., 2008).

As an example of what may be involved in moving towards a centralised review system, Cobb et al. (2019) reported on a National Institutes of Health (NIH) initiative in the US to establish a national IRB ‘reliance network’ to support national adoption of single IRB (sIRB) review. A reliance agreement is “a formal, written document that provides a mechanism for an institution engaged in research to delegate [IRB] review to an independent IRB or an IRB of another institution” (John Hopkins University, 2023). Significant incentives to systematise and simplify reliance arrangements had been provided by a growth in regional and disease- or population-specific IRB reliance agreements, as well as movement towards increased use of sIRB review of multi-site research through changes in federal regulations (Cobb et al., 2019). The NIH funded development of a master IRB reliance agreement to support sIRB review across the Clinical and Translational Science Awards (CTSA) consortium (Winkler et al., 2015), which would be applicable across a wide range of human subject research, and later funded the Streamlined, Multisite, Accelerated Resources for Trials (SMART) IRB Platform (NIH NCATS, 2022) to facilitate national adoption and implementation – supporting compliance with the 2018 NIH Single IRB Policy (National Institutes of Health, 2016) and other sIRB arrangements. Following its introduction, the SMART IRB was widely adopted, leading to many institutions leaving previous arrangements in favour of the new platform; however, transition, adaptation, and learning remained an ongoing process as institutions navigated a shift in research oversight (Cobb et al., 2019).

Aim of the paper

Within this context, this paper provides a case report and commentary of the process and challenges encountered by the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA) through 15 years of engagement with IRBs in multiple sites in Ireland within the further context of the transition to the General Data Protection Regulation (GDPR) (European Union, 2016) and the Health Research Regulations (Government of Ireland, 2021) to support GDPR implementation in research.

IDS-TILDA ethical review process

The ethical approval process for IDS-TILDA has involved two main phases:

Phase One: Preparation

Phase Two: Application

The focus in this paper is to describe the range of activities and effort involved in the second phase – the process of application for ethical approval through the host institution and the supporting disability organisations. A summary of the process for Waves 1–3 is provided first, followed by an in-depth analysis of the application process at Wave 4.

The ethical review process for Waves 1–3

As a national study aiming to recruit a sample representative of the population of adults with intellectual disabilities aged 40+ years, IDS-TILDA was able to drawn on the National Intellectual Disability Database (NIDD) in Ireland as a sampling frame to randomly and, from the study’s perspective, blindly select the required number of participants at Wave 1 (McCarron et al., 2011). Overall, the application process for approval by the host academic institution at Wave 1 took two months from the formal application to granting of approval. The preparation of the application and supporting documentation took approximately six months prior to this, meaning an application period of up to eight months in total for approval within the academic institution.

Given that the NIDD is a register of people with intellectual disabilities who are supported and reported to NIDD by disability services in Ireland, recruitment of participants required engagement with those organisations, and this would include obtaining their ethical approval for the study. At Wave 1, a total of 138 individual service locations were involved in the study. As some IRBs managed ethical approval for multiple service locations, the study team was required to obtain separate ethical approval from 45 individual and regional IRBs. For example, approval by the IRB of one national service provider covered approval across 18 of its service locations. The subsequent approval process took a total of 18 months to complete (McCarron et al., 2011).

Having received ethical approval for Wave 1, for each subsequent Wave there was a requirement to complete a new ethics application for full review and approval by the host institution ethics committee (TCD REC). Following this approval re-affirmation was sought of the approval from the individual disability organisation IRBs who originally approved the study at Wave 1. For Wave 2 and 3, there was a willingness by individual organisation IRBs to consider the new written approval granted by the TCD REC for the next Wave, along with a letter from the Principal Investigator (PI) summarising changes between the Waves and requesting confirmation of continued support for the study. As such, a new full application for ethical approval from each individual IRB was not always required, greatly expediting the process at Waves 2 and 3. However, in some cases additional materials were requested and re-affirmation of approval was delayed particularly when requests had the potential to be inconsistent with the host institution approval terms for that Wave. At Wave 3, the overall process of obtaining reaffirmation lasted for six months. In some cases, the time needed to meet these local conditions delayed completion of data collection in those providers even though ultimately they were no major changes to what was approved by the TCD REC.

The ethical review process for Wave 4

This section provides a detailed description of the process for ethical approval at Wave 4 of IDS-TILDA

Initial Step: Application for ethical approval in the supporting academic institution. A formal application for ethical approval of Wave 4 was made to the TCD REC. Consistent with what was submitted in prior waves, the application included the completed REC application form along with 37 supporting documents, comprising different versions of letters to prospective participants, Participant Information Leaflets, consent forms, data collection tools, and other documents. There was significant prior work in reviewing existing and potential new measures and scales to include in the protocol, engagement with internal and external stakeholders including the Scientific Advisory Board and Steering Committee, and with individuals with intellectual disabilities to develop and review the protocol and accessible materials. Feedback from the TCD REC on the initial application required only minor amendments. A revised application addressing these points was submitted to the REC and full ethical approval was granted. The process was completed in two months.

A significant change at Wave 4 was the need to consider new regulations addressing the newly enforced GDPR regulations (European Union, 2016) and the related Health Research Regulations (Government of Ireland, 2021) guiding implementation of GDPR for health research:

While not a requirement when the application for ethical approval was originally submitted to the TCD REC, a DPIA and a number of DPAs were subsequently developed and approved by the TCD Data Protection Officer (DPO) ahead of the start of W4 recruitment and data collection. Similarly, a Consent Declaration was obtained from the HRCDC to facilitate data collection with participants who did not have the capacity to give explicit consent.

Application for ethical approval at supporting disability services. Following confirmation of approval by the TCD REC in January 2019, preparations for ethical review by the supporting disability services across the country began in February 2019 with administrative support and communications to advance the process. The number of individual IRBs approached had increased from 45 in Wave 1 to 48 in Wave 4 with the addition of new services participating in the study. As with Wave 1, some of these IRBs managed ethical approval for multiple service locations, with the total number of study sites at 101 for Wave 4.

Process and timeframe for ethical approval by supporting disability services:

Beginning at the end of January 2019, initial contacts were made by phone and email to establish and re-establish contacts with key personnel at each site, and to alert them of the pending application for ethical approval. Formal requests for the affirmation of ethical approval were issued to all 48 supporting organisations by May 2019. Ethical approval from these individual organisations was sought on the basis of the approval already granted by the TCD REC, as well as the organisations’ established knowledge of and relationship with the study, which had been built through previous ethical approval and engagement in Waves 1–3 of the longitudinal study. A copy of the TCD approval was sent to each organisation along with a letter from the PI outlining changes to the protocol since the previous Wave, and seeking renewed affirmation from the organisation for the current Wave. A letter from the TCD Data Protection Officer stating that the study adhered to GDPR and HRR requirements was also provided.

Table 1 summarises the ethical application requirements utilised by participating organisations in Wave 4 and the length of time needed to obtain approval. Of the 48 individual organisations supporting the study, 43 (90%) granted ethical approval on the basis of the received TCD REC approval and the clarification of changes summarised in the letter from the PI. Two organisations required a full application for ethical approval be submitted using their own application/proposal form. One organisation required a full application (as if this was a new study) using a Standard Application Form (SAF) alone – the SAF is a standard ethics form developed by the Health Service Executive (HSE) in Ireland and used by a number of organisations nationally. One organisation required a completed SAF and a DPIA completed. And one organisation required a completed SAF with a DPIA and (following review and requests for changes) specific participant documents (e.g., PILs and consent forms) and other documents tailored to the requirements of the organisation.

For the large majority of organisations, therefore, approval was obtained on the basis of prior TCD approval and a supporting letter requesting affirmation. Among these 43 organisations, the majority (60%, 26/43) gave approval within four weeks, while a quarter (23%) took longer than eight weeks to approve. The average period to approve among organisations who accepted the affirmation letter was just 7 weeks. However, this was enabled by the significant amount of time not included in this figure that was spent by the Project Manager liaising with services and IRBs prior to the formal request for approval. Additionally, there was a wide range within this 7-week average – from same-day approval by some organisations, up to 44 weeks for others. The five organisations who took longest to approve using the affirmation letter took between 21 and 44 weeks to grant approval.

For the organisations which required more than the affirmation letter:

Level of engagement and follow-up with supporting disability services:

Table 1 also outlines the number of contacts with organisations throughout the ethics review process. Contact included emails and phone calls throughout the process. This shows that there was an average of seven contacts made with each organisation to achieve ethical approval, with a total of 326 contacts for the 48 organisations.

Outcomes/impact of ethical review by multiple IRBs

Almost 9 in 10 organisations/IRBs granted approval within 13 weeks, facilitating the commencement of data collection with individuals supported by their services within the planned study timeframe (September 2019). For six organisations/IRBs who took longer to formally approve (21–47 weeks), the commencement of data collection with individuals they supported was delayed between one and eight months. Despite the time taken to grant ethical approval, 47 of 48 organisations/IRBs (98%) were satisfied to proceed without any changes to the study documentation, including four of the five IRBs who required that new applications be made at Wave 4. There were no changes requested to the study protocol. In one case there was a need to change the study PILs and consent forms to meet their specific requirements but not in ways that had any impact on the study and its processes beyond the delayed start of data collection. Therefore, a critical impact of the process was the delay to the commencement of data collection within a small number of organisations. In the case of one organisation, the extent of the delay in their approval process resulted in the involvement in only part of the study by existing research subjects, as well as no recruitment of new participants from the organisation during Wave 4.