Chiltern Interview questions – Flashcards

Started clinical research as a coordinator. Obtained alot of oncology experience b/c was mainly focused on oncology clinical trials. From there became a cra with PPD. Talk about studies and phases. Talk about current protocols, and phases and number of sites. Several years of oncology experience, both as a CRA and as a coordinator.

Yes. The version I currently use is version 1.1. With RECIST there are 4 responses to rate how the patient is doing. Complete response, partial response, stable disease and progressive disease. Within complete response, it's considered the best result with all of the lesions disappearing. Within the progressive disease, this is the worst, with target lesion increasing in size by 20%. Patient also has progression if physician makes subjective assessment that non-target lesions has progressed or if there are any new lesions that have been found. Within partial response, if the sum of the longest diameter has reduced by 30%. This is a positive response, but not as positive as the complete response. Stable disease- the sum of the longest diameter doesn't meet the criteria for the progressive disease or partial response. When a response is being assigned to a visit, the non-target lesion and any new lesions are considered with the results from the target lesions.

Yes. I also have experience with radiation therapy. One of the studies I was on used radiation therapy. They used high-energy radiation to shrink the tumors and hopefully kill the cancer cells.

I've worked with a good number of difficult sites. MD Anderson is a current site. We had an upcoming datalock in the month of April. However, the site was not allowing for any monitoring visits b/c they had a change in their EMR system. They were transitioning over to EPIC. Therefore, they weren't allowing any monitors to come out in the month of April. However the deadline for the datalock was scheduled for the second week of May. So what I did was to schedule my monitoring visits immediately with them for the first week of May. I was there the entire week, and made sure we had everything ready for the datalock. They were ready and were able to meet the deadline for the datalock. With any site, I see myself as a partner to the site. I'm a one-stop shop for all of their study related solutions. I'm a resource personnel that they can turn to with any questions, problems and/or challenges relating to the study. Where I lack an immediate answer, I make sure to quickly find an answer or solution to the sites problem. Or point them in the direction where they can find the correct answer/solution.

Whenever I'm out of the office, I make sure that my email notifies people of that. However, I still try to respond to emails within 24 hours. I communicate with sites and study teams via email and phone. I like to set up weekly meetings with sites, in order to go over any issues or actions or questions that they may have. I'm in constant communication, via phone and email, with my sites on a weekly basis. Same goes with my team. Everything is documented on a telephone contact report here at PPD (just what was discussed with the site staff), and then it's uploaded to the trial master file for the study.

I've worked in phases 1, 2, and 3 oncology trials. I've done studies in solid tumors, which is what I'm on now. I've also done studies on breast cancer, and prostrate cancer. The oncology study that I'm currently on is a phase 1 and 2 first in human dose escalation study in patients that have advanced solid tumor. There's also an expansion phase in patients with ALK+ non-small cell lung cancer.

It's a phase 1 study, so the frequency of monitoring visits is a bit more relative to the other phases. Larger amount of SAE's. Lots of AE's. Typical of oncology studies though. Con-medications are a lot with a lot of the subjects.

There aren't neccessarily any challenges. It's really important for a CRA to understand what RESIST criteria are and how to utilize it correctly. It's good to know what it is, and to know what stage a patient is at. Are they at the progression stage, are they stabilizing, responding, etc.

I have seen a similar situation. The patient did have a partial response, there was a 30% decrease in the sum of the LD of the target lesion. PI didn't catch it for some reason. We had to retrain the PI and the entire site staff. They were retrained on RECIST criteria.

I am currently employed at PPD. I'm a home-based CRA. I've been with PPD for quite some time now. I have over 6 years of research experience. I've worked in several therapeutic areas... CNS, oncology, and infectious diseases. Within oncology in particular, I have over 4 years experience working in oncology. I've worked on phases 1, 2, and 3 clinical trials across all studies. Currenlty, at the moment, I'm working on 2 oncology studies, and a study on schizophrenia. The oncology studies are in phases 1 and 2.

Phase 1

That study is a phase 1 study. It's a multi-center, dose-escalation and expansion safety study. It's a pharmacokinetic, pharmacodynamic, clinical activity study of an early administered drug in patients that have lymphoma and advanced solid tumors also including gliomas within IBH1 and IBH2 mutations.

5. Sara Cannon in Nashville, TN, MD Anderson in Houston, MSK in New York and Mass Gen, and Dana Farber

With MSK, most of these sites, when it comes to the pharmacy, they are really strict. Before the visit, you have to schedule an appointment with the pharmacy at least 2 weeks in advance. For instance, with MSK, you have to take the shuttle, and sometimes there is traffic, and that will can sometimes result in a delay. But if you show up late, they will cancel your visit. With MD Anderson, they tend to hire a lot of new data coordinators and new study coordinators that are new to clinical research. So a lot of errors are made in the clinical trials that they're working on. Talk about datalock with MD Anderson and how you worked through it. With new site staff that are new to clinical research, I have to work very closely with them to make sure that I'm answering all of their questions correctly to prevent errors from being made. I also have to make sure to work closely with them so that protocol deviations are not being made.

Some of the measuring tools that I've been using are MRI's, spiral CT's, incremental CT's, computerized tomography CT scans, as well as the PET scans and fusion scans.

To evaluate how well the patient is doing, we use RECIST. With RECIST, there is usually 4 responses that would rate how well the patient is doing. There is a complete response, progressive disease, stable disease, and partial response. With the complete response, that's the best result with all of the target lesions disappearing. The progressive disease is the worst response, with the target lesion increasing by 20% in size. With partial response, it's when the sum of longest diameter of the target lesion has reduced by 30%. This is also a positive response, though it's not as good as a complete response. With the stable disease, this is when the sum of the longest diameter of the target lesions doesn't meet the criteria for progressive disease or for a partial response. So whenever a response is being assigned to a visit, the non-target lesions and any new lesions are considered with the results from the target lesions. The current version we're using is version 1.1

Yes

No, most of my experience is with RECIST criteria.

Prior to working in oncology, I had no oncology experience other than coordinator experience. But that was just 1 year, and it wasn't as a CRA. I was given a protocol, but I decided to take a barnett oncology clinical trial training. It was about a 7 to 8 week program, and this really helped me out a lot in oncology. I learned so much. I also took additional training on RECIST criteria, and watched a myriad of medical school lectures in oncology on youtube. I also read a lot of books on oncology. So I go about learning something new by immersing myself in that subject completely until I have reached a level of mastery that is satisfactory to me.

In the next 3 years, I hope to be a lead CRA in order to get some management experience. In the next 5 years I would like to transition into a role as a CTM, and eventually into pharmacovigilance.

I would definitely need to develop a great relationship with my sites, be extremely knowledgeable about the protocol. I would need to learn about the role itself, take trainings on the role. The way management performs is not the same as the way a CRA would normally perform.

It's used specifically to grade AE's in oncology. It runs from grades 1 through 5. The current version is 4.0. Each grade has a unique clinical description for the severity of each adverse event. For example, if a subject has an adverse event that's a grade 5, that means the adverse event is death or is related to death. A grade 4 would be considered to be an adverse event that is life threatening or whereby there has been an urgent intervention. A grade 3 is an AE that is severe or that's medically significant but is not really life threatening. There maybe hospitalization, or prolongation of hospitalization has been indicated. Grade 2 is a moderate, minimal, local, or non-invasive intervention indicated; limiting age-appropriate instrumental activities for daily living. Grade 1 is when symptoms are mild or asymptomatic. Intervention is not indicated and only clincial or diagnostic observations are being made.

Prior to the visit I would make sure that I prepare a confirmation letter to send to the site, that confirms my visit, and the time of my arrival to the site. It would also detail times for any meetings that will occur on the visit. I would document the visit in the CTMS within 2 business days of the visit. Then I would sure that when I do draft the confirmation letter, that it's going to be addressed to the investigator and study coordinator, and it will have the agreed upon arrival or start time. It will also include any activities I will be performing, outstanding actions from the previous visit and the estimated length of the visit. When I send the confirmation letter, I'll post it to the CTMS system. Then make all of my travel arrangements for the visit. 48 hours before the visit, I'll reconfirm with the site that I'm going to the site. I'll then prepare any supplies I need and update my outlook calendar with the visit details and the site contact information. I'll make sure that I activate my out of office email notification. Then I'll review previous trip reports from the site and if possible, try to remotely address any outstanding actions and items before the COV. Anything that can't be done remotely will have to be addressed on site. Site supplies and drug return: One of the major objectives at the COV is to assist the site with any in dealing with any unneeded study materials or supplies. Disposing of or retrieving all unused lab or study supplies (patient handouts, electronic diaries, etc). I would have the site generate a file note or similar documentation so there's a record indicating that study supplies were disposed of or moved offsite. I'll also ensure that the study drug logs are complete and that all study drugs are returned to the sponsor per instructions or destroyed on site according to the sites SOP. Then I'll ensure that copies of the return and destruction records are filed in the sites regulatory binder and that the copies are collected for the investigator site file. Essential documents: I would have the PI sign off on any tracking logs that were used during the study. The original goes in the sites regulatory binder, and I retain a copy for the TMF. A subject identity list needs to be created that lists the contact info for all the subjects that were treated (this stays at the site only as it has personal info on it). During the visit I'll make sure to ensure that regulatory documents at the site match the in house file. Documents to make copies of include site visit log, subject screening and enrollment log, delegation of authority log, proof of drug receipt, subject specific investigational product (IP) accountability logs, copies of temp/freezer logs, site initiation statement, training docs, overall site IP log, protocol/amendment signature pages, any updated 1572's, medical licenses or CV's, site communications to the IRB/IEC, and the IRB final status doc. Subject record: Check to see that appropriate versions of signed and dated informed consent forms are on file for every subject. You will also check that all source is complete (all lab reports and ECGs have been signed and dated with Clinical Significance assessed by the PI/Sub-I) and that all AEs/SAEs have been signed off by the PI/Sub-I and that they were followed to resolution as specified by the protocol. Finally, check that all significant Protocol Deviations (study procedures not conducted according to protocol, enrollment of inappropriate subjects, dosing errors, consenting errors, unblinding, subjects developing withdrawal criteria yet continuing in study, etc.) have been properly recorded and the sponsor/IRB has been notified as appropriate.I'll ensure that all CRF's are complete and submitted to the sponsor. All queries will need to be addressed. I'll also make sure that AE/SAE follow up is complete and that all signed informed consent forms (ICF's) are filed. I'll ensure that the investigator brochure and study materials are filed together. I'll also review long term storage. The final report is then completed and submitted to the IRB and sponsor (usually a form provided by the IRB). I would also address certain items with the PI and the site staff. Discuss with the PI his/her responsibilities including: query/data collection following the close-out visit, essential document retention, publication rights, and the necessity to update the Financial Disclosure statement if there are changes in their financial interest for up to one year following completion of the study. Finally, explain to the PI the potential for regulatory agency inspection and the requirement that the site notify the CRO/sponsor immediately if contacted for an audit/inspection.These items would be to outline the remaining investigator responsibilities that follow the site closure. Ensure that the IRB and ethics committees are notified of study closure. Do regulatory authority inspection, readiness reminder and procedure. The ICH/GCP regulation requirement of the updated FDF. I would remind them of the responsibilities concerning data queries that are issued after the COV. I would remind them of the record retention requirements, and I would explain to them about the sponsor publication policy and the notification procedure for a change of address. A final review of the IP accountablility, the destruction return, and the regulatory binder is going to be performed during the visit. While performing the final inventory of the study product, I'm going to be confirming that the study product received the disposition, return, and the destruction records, making sure they're accurate and that they've been complete.

A description of the study, a statement of the subjects privacy and confidentiality, and expected AE's or what the subject can reasonably expect as side effects.

The business draft is due in 5 business days, and the final report is due in 5 business days. I usually start my report when I'm at the site. I usually get a good amount of it done while I'm at the site, and then once I've left the site, I usually have the first draft prepped within 1 to 2 business days.

I don't really receive any major comments. For example, the last report that I submitted, I forgot to put an update on one of the issues and actions that were still open. But I don't get too many comments. Early in my CRA career, I was getting feedback about lack of detail in my reports.

I always like to make sure that I'm very professional as a CRA. I serve as a motivational force to enable my sites to exceed their expectations of the project team, and with that I'm able to develop a good relationship with them. I make sure that I'm able to answer all of their questions in a timely manner, serve as their one-stop shop for any questions, or study related problems that they may have. I want to make sure that they are able to come to me with any questions or challenges pertaining to the study. Whenever I can't give them an immediate answer, I try to answer as soon as possible or point them in a direction in which they can find the solution they are looking for. With this type of perspective of being a site manager to your sites, it has enabled me to forge strong relationships with my sites. I also make sure to compliment my sites when they are doing are a great job and to try to motivate them when things are running slowly by encouraging them.

I'm making sure that the records of receipt are on file for the drug. I go into the IBRF system and print out the report for the IP for when I will be on site. However, if the study is not utilizing an IBRF system, I would make sure to verify that the records of receipt are on file and that they've been signed appropriately. I would then submit the signed copies to the TMF system. I'm also going to verify the IP against the site shipment records, and verify accuracy of the dispensing of the products as well as the subjects site accountability records. I would make sure to perform subject dosing at 100% and make sure no subject has been over or under dosed. That would include dosing records and investigational product accountability. I would confirm that all subject-specific IP dispensing and return has been documented in the IP accountability log or the site comparable log. If the site has an SOP for destruction, and it hasn't already been filed in the TMF, I would make sure that it's filed in the TMF system as well.

Firstly, I would check the delegation of authority log to see if there is a back-up coordinator. If there is a back-up coordinator, and she is on site, I would try and work with her. If not, I would have to go about my visit completing as much as I can without the coordinator being present. I would perform my regular RMV without the coordinator being there. I would make sure my team is aware that she is no longer at the site. If I don't have a site visit the next day, and there is a possibility that a back-up coordinator can be on site the next day, I would ask my team if I could stay an additional day on site, and also see if the site staff can accomodate me for the next day. However, if I do have a site visit the next day, I would try and rearrange that visit, so that I can have an additional day on the present site, and arrange with the back-up coordinator to work the following day. With the coordinator that quit her job and left the site, I would ensure that all copies in the regulatory binder have been updated, and if there are any new site staff, I would ensure that they have been added to the delegation of authority log, and that all training has also been applied.

What do you think would be crucial for my success at chiltern? What do you enjoy most about working with chiltern? What should I expect after this interview?

So far only 1 in oncology and that was a solid tumors study.

Yes, it is a phase 1 study. It's a first in human dose escalation study in patients that have advanced solid tumors. It also has an expansion phase. The investigational product has a 25mg capsule and 100 mg capsule. The doses are from 25 to 250 mg. Basically, there are a lot of drug related AE's. There has been a fluid overload. A lot of patients have experienced rash and TMA's of grade 4. The efficacy results of the study were responses observed in patients that had CNS metastasis. 7 of the 12 responders remained on the treatment and there was a median duration on the treatment of 8 cycles. There's up to 100 patients, about 12 sites. The end-dose escalation, there was advanced solid tumor malignancy. In the expansion study, there are patients with ALK+ genomic alterations.

Patients had to have an NSCLC with ALK genomic alterations. They had to be positive by fish, and they also had to have the ability to swallow and retain oral medications. They had to have an adequate organ system function. There was an operationally defined definition for that in the protocol. They also had to have an ECOG performance score of 0 or 1.

It was part of the inclusion criteria, but the study staff were somewhat lenient on their references for the patients ability to conduct their activities of daily living, though this depended on the patient.

It was used to measure the cancer. There were 4 responses to measure how the patient was doing. The 4 responses were the complete response (CR), partial response, stable disease, and progressive disease. A complete response was given if all of the lesions disappeared. Progressive disease was the worst response and was given if the target lesions increased by 20%. The patient was also said to have progression if the physician made a subjective assessment indicating that the nont-target lesions had progressed or if any new lesions had been discovered. The partial response was given if the sum of the longest diameter of the target lesion reduced by 30%. Now if criteria for partial response or progressive disease was not met, then the response of stable disease was given. When a response was assigned to a visit, the non-target lesion or any new lesions were considered with the results of the target lesions. In this study in particular, confirmed responses are really called for, and that was just required at 2 consecutive visits before the patient was assigned that response.

That was used for the grading of the severity of AE's. It would display a grade of 1-5. Each grade had a unique description for the severity of the AE. A grade 1 was for mild symptoms, grade 2 was for moderate or minimal, grade 3 was for medically significant, but not immediately life-threatening, grade 4 is life-threatening, and grade 5 is death resulting from AE's. So this was used to grade the AE's. A lot of the sites struggled with this. They would grade some of the AE's a certain grade that the medical monitor would not agree with. So a lot of training had to be performed on criteria of that nature.

yes. For example, for some of my sites, they would give a subject a grade that the monitor disagreed with. For instance, if there was a rash or something of that nature, or let's say anemia. And the hemoglobin was from 10.0 to about 6.2. The site would give a grade of 2, and the medical monitor felt that the grade should be 1. So there was a lot of back and forth, involving the CRA having to go back to retrain the site staff and PI on how exactly to grade each AE properly.

No

There was a PI I was working with, and he was not showing proper oversight of the study, because he was not meeting with me during my monitoring visits. I would schedule these monitoring visits with him, he would accept the invitation, but wouldn't be present during the visit. So within 10 days, I would schedule a follow-up visit with him and he would accept the meeting invite and not call in. So basically, this continued to happen, and I felt maybe it was a communication error on my part, or it could be that he just wasn't cooperating. So I did my best to communicate to him effectively, the importance of him needing to maintain adequate oversight, and that him being able to meet with me during my monitoring visits would suggest that he has adequate oversight. But he still wasn't communicating effectively. So it got to a point where it was out of my hands, and I had to inform my team about the situation. I basically told them the PI has not been compliant, he's very unresponsive. They advised me to continue communication with him, and to see if he would meet with me at the next visit. I did as they suggested, and yet again, he wasn't present at the meeting. So my team escalated this situation to the sponsor. The sponsor had to reach out to the PI before he was willing to respond. Afterwards, he finally met with me during my visits, and fortunately for me, he was very apologetic. He explained that he had a very heavy workload, and I explained to him that I would arrange my visits based on his availability, to make things easier for him so that he can at least be present for every other monitoring visit. So going forward, things have been running smoothly with the site.

I would make sure my team is aware of the situation. If the IMV is going to be performed out of window, based on the sites availability, I would make sure my team is aware of this. Talk about data lock with MD Anderson example. This happened to me in the month of April. For that month, the site wasn't allowing any monitoring visits because they were undergoing a change in their EMR system. They were transitioning to EPIC. So, with that being said, the last visit was conducted in the first week of March, so that would def make it out of window if I couldn't go back to the site in April. So I made sure my team was aware of that. The sponsor approved of the out of window deviation, and during the first week of May, I made sure to be at the site for the monitoring visit.

With one site I was working with, they were having a lot of problems with the EDC system that the study was using because they weren't familiar with it. As a result, they were not following the data entry timeline requirement. They weren't putting data into the EDC within the 24 hour timeline. So I let the team know that the site wasn't familiar with the EDC from what I had observed (omnicon). So the team provided additional training. Although they were trained during the SIV, and the PSSV, we still went ahead and provided additional training for them to get them to be more familiar with the EDC system. We trained them on that, and I ensured that before any of my monitoring visits, I would go into the EDC and ensure that all queries were responded to and that all data had been entered. I created a tracker to document any outstanding queries and missing pages, and I continued to follow-up with them via phone and email. So this pushed them to start entering data into the EDC within the required timeline and to start responding to queries in a timely manner as well.

I'd like to travel less, and be with a company where I can be a valuable asset and expand and grow my career. I'm just another CRA at PPD, just another number. Also looking for better work-life balance.

At PPD, our draft is due in 5 business days and the final is due in an additional 5 business days.

I have a habit of writing my report at the site. I start a handful of the report at the site, and then complete it once I leave the site. So my reports are usually done within 3 business days. I review reports for CRA 1's, so it helps me to be on top of my reports.