Pre-Study Visits and Site Initiation Visits

Clinops toolkit study monitoring visits and site initiation

Pre-Study Visits

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).

Objectives of a Pre-Study Visit

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.

Clinops toolkit prepares for investigator meeting
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.

Site Initiation Visit Complete at an Investigator Meeting

The initiation of a site can sometimes occur at an Investigator Meeting (IM) where all the potential investigators are brought together in (a typically quite fancy) hotel or other conference arena to receive group training on the new study. More often, however, this will actually take place – on-site. This is usually a 4-8 hour visit and you may be accompanied by a Project Leader, Medical Monitor, or even Data Management personnel just depending on the desire of the sponsor. Before your visit, you will coordinate a convenient time for the study site and confirm your visit with a letter informing them when you will arrive and what the objectives of the visit will be. It is important to physically be at the site so, as a monitor, you can visit the labs, pharmacies, and other areas where the research will be conducted to ensure they are adequate. For example, both labs and pharmacies should have restricted access and the site should know where it will store the Investigational Medicine/Product (IP) and this location should be locked. If the site will be storing blood or tissue samples, you will inspect their freezers and ensure that they maintain adequate temperature logs and have standardized sample handling protocols and training.

Training and Study Overview

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:

Introduction to Monitoring
Home from the Investigator's Meeting
About The Author

The Lead CRA

Nadia started The Lead CRA blog in 2007. She is now lead author for ClinOps Toolkit. Nadia is currently working as a Clinical Program Manager at a small specialty pharmaceutical company in the San Francisco Bay Area. You can reach Nadia via email at leadcra@clinopstoolkit.com anytime.

24 Comments

  • Dhoundiyal

    September 12, 2015

    IF Phase IV is being conducted , post market clinical study with an FDA-approved drug. One of the sites that participated in the Phase III clinical study for the investigational drug feels that they don’t need to redo the Site Initiation Visit (SIV), since the last study ended less than six months ago. Plz answer whether the site would be exempt from the SIV, with specific references to drug accountability, IRB/IEC approval, and monitoring.

  • Kadi

    July 8, 2015

    I am taking a class at UC Berkely. The questions I ask is ” if I am conducting a phase IV post marketing clinical study with an FDA approved drug. One of the sites that participated in phase III refuse to redo a SIV cos the last one was less than 6months. Can they be exempted from the SIV ?

  • Anonymous

    April 14, 2014

    Thank you for helping me understand better the Clinical Associate role. I gained a lot coming to this site.

    Tai

  • Stamatis Pantsios

    November 29, 2013

    1.Is it possible to start the close out visit even though the recruitment period has not been finished and the number of patients needed for the study has been gathered and they have finished their visits?
    2. What are the essential docs that hat should be ready in order to conduct an initiation visit?
    3. Is it obligatory the medication to be on site during the Initiation visit?

    Thank you for your reply!

  • sarosh kamal

    April 10, 2013

    Hello, Can I get a resource to a sample questionnaire to ask the PI, in a clinical investigator selection and qualification visit

  • Jennifer

    February 20, 2013

    I’m sorry SIV…Thank you, Jennifer

  • Anonymous

    February 20, 2013

    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.

    • The Lead CRA

      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.

  • Iuliia

    October 23, 2012

    Hi Nadia, could you please clarify if there is general requirement that SIV report should be filed in ISF. Thank you in advance Iuliia

    • The Lead CRA

      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.

  • claudia

    February 16, 2012

    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)?

    • The Lead CRA

      The Lead CRA

      February 24, 2012

      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.

  • The Lead CRA

    The Lead CRA

    September 12, 2011

    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.

  • Melissa

    September 9, 2011

    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?

  • Anonymous

    April 30, 2011

    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.

  • The Lead CRA

    The Lead CRA

    November 27, 2010

    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!

  • Anonymous

    November 26, 2010

    Post SIV can site share ICF with pre-identified patients prior to IMP recept at the site?

    • Anonymous

      February 19, 2012

      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?

    • The Lead CRA

      The Lead CRA

      February 24, 2012

      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.

  • Anonymous

    April 26, 2010

    Thanks for a great job 🙂

  • Anonymous

    January 5, 2010

    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!

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    November 7, 2009

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  • Kat

    February 13, 2009

    Cool blog, will visit more!

  • Anonymous

    June 22, 2008

    Nice review of PSVs and SIVs!

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