It is now several months since Bellberry updated its procedures and we are pleased to report that there has been a significant drop in start-up times for additional sites.
The table beneath is a comparator of Jan/Mar 2020 to 2021. These months have been chosen as Jan/Mar may pre-date any COVID related issues sites may have, and in December 2020, the grace period ceased.
|Approval-Month||Count of Applications||Average of Bellberry Days|
Amendments are tracking at the same turnaround time in Bellberry days (3.8 days). The updated model’s difference is we now ensure all sites are listed on the one approval letter, as appropriate.
We appreciate the teething issues as sites, sponsors, and our administration tackle the changes together. If you have any questions or you would like to schedule a call with the quality team to discuss the practicality of the changes at your site, please email email@example.com.
We recently made some minor changes to some of our documents and guidance for researchers. A summary of the changes can be found here.
FAQs relating to the process changes rolled out in late 2020
Typically, we get sites to submit a radiation report from their local physicists that will contain their site-specific radiation wording for the PICF. Under the new set up, does Bellberry want the actual radiation report to still be submitted, or can sites just use the Site-Specific Clauses form for their site-specific radiation wording?
The Committee will want to see the radiation report (if above standard of care) and the wording from that report placed in the site-specific wording doc. The HREC notes the radiation report, whereas they approve the site-specific wording.
If the lead has already imbedded the radiation report wording of multiple sites into the Master PICF, then it would not need to be put in the site-specific doc.
Does every participating site need to submit a site-specific clauses document, even if they have no changes to the Bellberry Master PICF? If every site must submit this document, even if there are no changes, hasn’t this process created another document for sites to complete rather than just submitting the Site Specific PICF?
Yes, if the lead selects pathway 2.
It is for the following reasons:
- The sites are submitting it to confirm they aren’t making changes.
- If there are ethical changes, then the RGO/other institutional representative has a point of reference that the HREC has reviewed the wording, and it is OK for inclusion. We hope that it can help with making the line clear between what is ethics and what is governance. Governance is then about adding administrative items (headers, footers, logos, local site complaints).
- The real value in the document is post-approval. If the site is not changing any site-specific content, they are free to create a site-specific PICF on the same day as the Master is approved. Historically, they may have created it, but they would then need to submit it to the HREC and await approval. In discussion with sites, we found our former approach caused issues when a Master PICF had urgent safety updates, and sites were then waiting for their site-specific PICFs to be approved post Master.
When we audit a study, if we find ethical changes to the site-specific PICF that were not submitted in the site-specific clauses document, we will bring it to the PI’s attention. We recognise there is no clauses document for historical studies, so we would go by the previously approved site-specific PICF.
Does the Master PICF version & date have to be referenced in the site-specific clauses document? This won’t be possible if the site-specific clauses document is submitted at the same time as the draft Bellberry Master PICF.
No, the site does not reference the version and date. The site only needs to reference which document their wording is going into (e.g. Master Main, Master Pregnancy).
If the lead has chosen pathway two, and each site has submitted a site-specific clauses document, if they never wish to change any ethical content in their site-specific PICF, we will never receive an update to that document for the rest of the study.
The clauses document is approved, and each time the Master is updated, they include their approved clauses in their site-specific version, which is approved via whatever mechanism they choose for their own site (e.g. Clin Trial Manager go-ahead, CRO sign off etc).
The naming convention for the site-specific clauses document is not listed in BA G12. Can this be added? Our suggestion is that it should be “Protocol Number_MyHospitalAcronym_Site Specific Clauses_Version#_DD/MMM/YYYY”
Great suggestion – the change has been made and the document has been republished on our website.
Our Master PICFs can have optional wording in the body of the PICFs so sites can select the relevant statement for their site and delete the other e.g. 2 radiation statements. Which of the 2 options below is correct?
- Does not need to be listed in site-specific clauses document as the wording has been ethically approved in the Master PICF, so site deleting the not applicable section would be a known admin change.
- Copy and paste the deleted wording into the site-specific clauses template stating that it is not applicable and therefore deleted.
The correct answer is option 1.
Another scenario: There are 4 sites as part of a multi-centre study, and the lead site has chosen PICF pathway 2 and submitted the Master PICF + their site-specific clauses. All other sites have submitted their site-specific clauses prior to EC approval. EC has queries about Site 2 and Site 3’s site specific clauses document. Does this hold up the initial EC approval letter for the Lead Site and Site 4?
No. It only holds up the site/s in question. Suppose it is something minor that could be dealt with swiftly. In that case, we will encourage our team to rectify the issue so approval for all sites can occur on the same day. If it appears that is not likely, sites 1 & 4 would be approved. Then, sites 2&3 would be approved when they have resolved their issues. Sites 2&3 are then provided with any approval letters that have been issued for the other sites if there are documents on there that are relevant to them (e.g. protocol, IB, Master PICF).
Can you please clarify if the statement “submit a full application” is still correct under this new process? I thought only the submitting site (which is no longer limited to the lead site) has to submit the full application and now BB will be helping link additional sites to that full application.
The BB website lists the FAQ below:
“If the lead site has yet to be approved please submit your site application via eProtocol, however you do not need to attach any study documentation on page 7 of your application. If your lead site has already received HREC approval you will need to submit a full application including all your site’s study documentation on page 7”
In this context, we define ‘full application’ to mean each site must complete an application in eProtocol and answer all questions. We don’t wish for the definition of ‘full application’ to relate to the uploading of core study documents such as the protocol, IB etc.
The additional sites are only responsible for uploading documents relating to them. The sort of items we would expect to see uploaded:
- CV if not current within 12 months.
- A site-specific form – if applicable.
- Any other site-specific documentation that is not relevant to other sites – e.g. social media plan or local advertising.
Local procedure for document management. Our internal quality team and some sites are interpreting the statement below to mean that sites need a SOP of some form for their site-specific documentation. This is not always going to be the case, especially with very small private clinics. I don’t know if this is the intention of the statement so I would like to understand from your perspective.
“Sites are no longer required to submit tracked and clean site-specific PICFs and other site-specific participant facing documentation to Bellberry. This change allows sites with research governance offices (or other formal institutional arrangements for reviewing site-specific documentation) to go ahead without the need for further HREC review. Sites that do not have a formal institutional arrangement will be responsible for developing a local procedure for document management.”
Best practice would have sites documenting their procedures, but how each organisation manages its documentation is their decision. Individual organisations will be held accountable for adherence or non-compliance with whatever process they put in place. For example, if a site consents a participant on a superseded version of a PICF, a Sponsor may analyse the sites internal process to identify gaps.
The lead site at the initial submission has chosen pathway 2. One of the additional sites submits a protocol amendment during the study and their documentation is aligned with pathway 3. They have now re-aligned the PICF pathway. Is that possible?
The HREC administration keeps a record of the lead site’s PICF pathway at the initial submission. If a site tries to change the pathway, the HREC administration will return the documentation, along with an explanation that it does not match the study pathway. The only exception to this would be when a single centre study on PICF pathway 1 has changed to a multi-centre study. The Sponsor needs to determine who is responsible for unpacking the PICF and moving the study to PICF pathway 2 or 3. In this case, the submitting site should also explain the change in the pathway to the HREC. Providing as much information as possible will help the administrator understand why the documentation change is being submitted.
My site is ready to submit in 2021, but the lead site and other additional sites were approved in August 2020. No other sites have been added since Bellberry updated its submission process. How do I know what pathway I should follow?
Please contact the Sponsor and get them to confirm with the site that submitted the initial application (lead) which pathway they would like the study to follow. Once you have confirmation, please attach any email correspondence that confirms the pathway and upload it with your application. If there is no correspondence, the HREC administrator will need to contact the lead site and ask which will potentially delay approval for the additional site.
If the lead site was approved before the submission changes, do they need to submit anything when a new site is added?
The lead site only needs to choose a pathway. There may be some situations where updated documentation is required, but it should be rare.
For example, if they pick pathway 2, they do not need to send in site-specific clauses documents if we have already approved their site-specific PICF. Sites approved before the PICF pathways only need update the HREC with a site-specific clauses document if they are changing the wording from an already HREC approved site-specific PICF.
If the lead site chooses pathway 3, the only update required is if the Master PICF does not cover the requirements of the additional site that is being added. E.g. the radiation statement has two options, but the new additional site has different wording that isn’t already covered. The lead site would then need to submit an amendment with an update to the Master PICF. The amendment can come either before or after the additional site is approved. If it comes post-approval, the additional site will be delayed in creating its site-specific PICF. This is a matter for Sponsors and sites to work out what suits them best.
Can I submit an electronic indemnity listing all sites even if those sites are yet to submit to Bellberry?
Please only submit electronic indemnities listing sites that have applied or are due to apply in the coming days. Bellberry will not execute indemnities that list sites that have not applied eProtocol.
If the indemnity is on paper, Bellberry will strike through the sites that haven’t applied in eProtocol.