Depending on the company you work for and the Standard Operating Procedures (SOPs), you may be required to complete an in-person Pre-Study Visit (PSV) before an investigator is initiated to join a clinical trial. In some cases, you may even be able to perform this via telephone, web-conference, or it might be waived altogether (say, for example, an investigator your firm has collaborated with in the past 18 mos or so).
The objectives of a pre-study visit are to review the adequacy of the site, the training and experience of the study staff, the access to the right patient population, and the site's interest in the study. If the site isn't motivated or if they are already participating in studies that would compete for the patient pool, they may not be a good recruiter. It is expensive to start up a site, monitor them, and supply them with all the study materials and training. Ideally, you would only open sites that would perform well but in reality, there are always 'dud' sites in every study (Read my related post on Selecting Qualified Investigators). This is typically a 2-4 hour visit. After your visit, you will likely need to complete a report template or assessment and send a follow-up letter to thank the site for hosting you and inform them whether or not they have been chosen to participate in the study.
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| At an Investigator Meeting there may be presentations and break out sessions to answer questions and train study staff with the skills required to properly execute the protocol. |
During your initiation visit you will probably spend a great deal of time training or reviewing the study protocol design and answering questions from the site personnel. You will also want the Principal Investigator (PI) to be available for specific parts of your presentation. Specifically, you will need to discuss the Investigator's Responsibilities as related to the regulations to ensure there is agreement and understanding (The investigator may choose to delegate some of his/her responsibilities but ultimately, they will be responsible for all actions and conduct of the study. Specific study related activities can only be delegated to those who posses adequate training and experience -- a secretary cannot perform a Physical Exam, etc.); You will explain publication policies and documentation responsibilities; You will inform the PI that you will need timely access to subject's records and the acceptable time frame for completing patient data case report forms (CRFs) and answering queries regarding the data). Document everything that is discussed so you can add it to your report and if there are any questions that are unresolved at the end of your visit, you can include resolution for those in your follow-up letter after the visit.
Email me if you have more specific questions. Now that our study is underway, next time I will discuss how and why we complete routine monitoring visits throughout the study conduct period.
You may also like...from The Lead CRA archives:
- Selecting Qualified Investigators April 2010
- Routine Monitoring Visits March 2008
- Close-Out Visits July 2008
19 comments:
Nice review of PSVs and SIVs!
Cool blog, will visit more!
Your blog keeps getting better and better! Your older articles are not as good as newer ones you have a lot more creativity and originality now keep it up!
Thanks for a great job :)
Post SIV can site share ICF with pre-identified patients prior to IMP recept at the site?
Hi and thanks for your question. In my current trial all of our sites consent and screen prior to receipt of Investigational Product. We are keeping the inventory really tight and first shipment is only triggered after a second qualifying screening visit (4 week screening window with up to 40% screen failure rate).
In order to consent, our SOP requires that the site is authorized for drug shipment, rather than drug actually physically on site. In order to authorize drug shipment the site must have 1) completed the SIV 2) received IRB approval for protocol, ICF, Investigator's Brochure (IB), and all PRO instruments 3) Submitted complete regulatory document package to sponsor (1572, signed/dated w/i 1 year CVs for all personnel on 1572, Financial disclosures, Protocol signature page, IB signature page, etc. (some of this package goes to the FDA before the trial is initiated at the site) 4) fully executed contract and budget 5) written activation letter from sponsor. At that point the site can begin distributing ICFs for signature. Hope that clarifies!
This is an amazing site. I have often looked for a resource like this to refresh my memory on several salient aspects of my CRA duties. Thank you.
Do sites HAVE to have an SIV? Especially for a simple data collection study? Or is a web training sufficient for sites that have done research with us before?
Hi Melissa, it sounds like you may be working on a non-interventional observational study (so no medication or any special assessments or survey instruments are given. For your study, perhaps you are just reviewing standard data that would be collected in the course of normal clinical conduct). In that instance, you may be able to do a web training for sites that you know and have worked with recently. Without an in-person visit, however, how will you be sure that the facility remains adequate and that the study can be conducted there feasibly? As sponsors, we are obligated to ensure that the people working on our studies are qualified by education and experience. You could do that remotely by reviewing CVs and monitor reports for other studies. I hope this addresses your question. certainly there is a trend to not have expensive Investigator Meetings and I have worked on many studies where the PSV is combined with an SIV. It is more rare for me though to work on a study where there is no SIV at all. If you won't be performing SIVs definitely document at the sponsor level TMF how you determined the sites were qualified and trained.
Hi Nadia,
Thanks for all the effort you put into this amazing educational blog.
Question...You mentioned above that at the SIV the monitor needs to be at the site to visit the labs, pharmacies and other areas where the reearch will be conducted. Wouldn't the monitor do this during the PSV (qualifying visit)?
Hi Nadia, I am very great full for such a amazing site. i am regularly reviwing your site to know more about CRA responsiblities. i have one question regarding the patient consent form.
as per GCP can the patient sign the consent form in home and then doctor can sign the form?
Hi Claudia, you have a great point. If the monitor has already visited all of the facilities where the research will be conducted, they may not be required to go to them all at the SIV. This is going to be determined by your companies SOPs and the monitoring plan. Remember that the PSV can sometimes be waived or combined with the SIV. In that instance, especially if it is a site you are not familiar with, you are well-advised to visit each location. Thanks for a good question and I hope that I have clarified enough.
I have written a Q&A response post to provide additional guidance on the consent process here. Your question is specifically, can a patient bring in a signed consent and then the doctor could counter-sign. I don't think that the regulations prohibit this and I am aware that there is a trend for study sites to either let the patient take home a copy of the consent to think about and discuss with their family or to mail out a blank form in advance of an upcoming visit where the study will be offered. The investigator does have a responsibility to ensure that the subject has adequate time to ask questions and also that the consent process is a discussion, not just paperwork (GCP 4.8; 21 CFR part 50b & part 312.60).
If I were monitoring a site where the subjects have been instructed to sign the forms at home before the screening visit I would recommend to the PI that this process be revisited as it is not adequate.
Don't forget to remind your sites that there is a requirement in 21 CFR 312.62(b) that "the case history for each individual shall document that informed consent was obtained prior to participation in the study." So it doesn't say that you have to consent at the clinic, but remember an ICF form is a document that supports that the consenting process took place appropriately and in accordance with the law and regulations.
To re-state, shortcuts to the consenting process are a really bad idea and I would recommend you train your sites to demonstrate greater vigilance and attention to the ICF process.
Hi Nadia, could you please clarify if there is general requirement that SIV report should be filed in ISF.
Thank you in advance
Iuliia
Hi,
Does the PI/Co-investigators have to sign the investigator agreement and financial disclosure before or at the time of the pre-site monitoring visit? The IRB has already approved the site for the study.
I'm sorry SIV...Thank you, Jennifer
Hi Iuliaa, According to ICH E6 GCP Section 8.2.20 a copy of an initiation report should be filed in the Site Master File and Trial Master File.
I've worked at many CROs where we filed a memo/summary of findings, follow-up letter, or abbreviated SIV report to satisfy this guidance and at the sponsor's request. For many simple short trials, the PSSV is completed remotely or even combined with the SIV, and especially in these cases there may be subjective criteria evaluating a Pi's past performance in other trials; this is not something you would necessarily want to share with the site you are starting a relationship with. I hope that clarifies. The guidelines really just suggest that you document a) that the site is suitable to conduct the trial and b) that trial procedures were reviewed with the investigator and the
investigator’s trial staff prior to initiating the trial.
Hi Jennifer, thanks for clarifying that you intended to write SIV rather than PSSV. Just to elucidate for other readers typically, PSSVs occur as part of site feasibility and before an investigator agreement or IRB submission occurs (since these two activities consume time and resources that the study team would not necessarily devote to a site that has not yet been selected to join the trial).
In this case, you are saying an SIV is occurring after IRB approval and asking, is there a requirement that the Investigator agreement has been executed and Financial Disclosure Forms (FDF) have been collected?
In my experience, I have initiated sites where the investigator agreement is not yet fully executed. This is not a best practice but is sometimes necessary when site startup is time-constrained or extremely condensed and you are doing several start-up steps simultaneously.
Ideally, at the conclusion of an SIV, the Investigational Product should be on site, the IRB approval in place, and the site should be free to enroll. However, without a fully executed investigator agreement, it is absolutely not appropriate to consent subjects because legal issues such as privacy, indemnity, insurance, reimbursements, etc. are not yet fully defined and agreed upon.
So in short, you can perform an SIV without the signed investigator agreement but you should not fully "initiate" the site and allow them to begin the trial yet. I can think of many SIVs I performed where I actually collected the final contract during the visit. Again, completing the investigator agreement after an SIV is a bad and risky practice.
You also asked me about FDFs. I'll probably queue this up as a future blog post as this topic is very misunderstood. Financial Disclosures are only important in the context of a New Drug marketing Application (NDA) submission; we're talking years later after all the supporting trials are done -- not technically at the time of initiation for a particular study.
It is a sponsor's responsibility to assure the agency that investigators did not have undue influence in the trial because of financial interest. The FDF is a form the sponsor keeps to document that they satisfied this requirement and in the NDA they use another mechanism to confirm that it was done.
Example of some other FDF items commonly not understood: if you do a Phase I trial, large open-label safety study or clinical pharmacology trial, FDFs actually aren't technically required and for Phase II, if you read between the lines of CFR part 54.
The sponsor confirms FDF at the end of a study.
The Investigator has the obligation to update the FDF form for up to one year after the trial if anything changes, not the sponsor.
So this is per the regulations, but remember that your work is governed by your SOPs which are actually derived from the regs and guidelines. Always check with your study lead for your trial-specific requirements as they may be more conservative.
Hello, Can I get a resource to a sample questionnaire to ask the PI, in a clinical investigator selection and qualification visit
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