MODULE 10: SOURCE DOCUMENT VERIFICATION, DATA

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MODULE 10: SOURCE DOCUMENT VERIFICATION, DATA

MANAGEMENT AND THE TRIAL CLOSE-OUT VISIT EXAM

QUESTIONS

Actual Qs and Ans Expert-Verified Explanation

This Exam contains:

-Guarantee passing score -25 Questions and Answers -format set of multiple-choice -Expert-Verified Explanation

Question 1: CRA approaches to source verification - first review CRFs

Answer:

Review one patient's CRF for missing data, blank fields, inconsistencies, logical errors and consistency of data between visits. Advantages: a quick scan of the CRF allows the CRA to be familiar with the patient, to be on the lookout for SAEs, concomitant meds, etc. It enables the CRA to project the time needed to review additional cases.

Question 2: Study close out visits - final monitoring activities

Answer:

CRA does final accounting for IP. Retrieval of study supplies. Reconciliation of the essential documents (reg binder) to assure completeness. Review ongoing obligations of investigators, (e.g., final IRB reports, records retention). Clarify any remaining sponsor commitments (e.g., grant payments, publication rights, future studies).

Question 3: SDV FDA guidelines

Answer:

Adequate records of subject identification, clinical observations, laboratory tests and drug receipt and disposition are maintained by the investigator and reports submitted by the investigator in support of the safety and/or effectiveness of the IP are timely , adequate and accurate.

Not specifically required in the FDA regulations, the FDA considers data verification against source documents one effective way to ensure the accuracy of clinical data, along with centralized monitoring techniques.

Question 4: Authenticating the data

Answer:

Most cases of questionable data are merely the product of carelessness and are not criminal intent, although cases of data fabrication do exist.

Question 5: Reasons for study closure

Answer:

• trial completed as planned 2.) trial discontinuation (e.g. analysis of the data indicates safety problems

or drug/device proven effective and trial no longer necessary. Site specific problems - little or no enrollment, protocol/regulatory compliance issues, etc. Ethical issues - the sponsor may halt a study due to a change in the overall risk/benefit ratio of a drug/device (based on new information)

Question 6: To ensure accuracy of clinical data

Answer:

The CRA is expected to review a representative number of the CRFs and compare them with the investigator's original source documents. The amount of source document verification to be performed is usually defined by the sponsor, prior to study initiation, in study specific guidelines (e.g. sponsor monitoring plan)

Question 7: Sponsor approaches to source verification - 100% approach

Answer:

The CRA verifies 100% of all data fields on every page. Advantage: close to full assurance of accuracy

of all data. Limitation: very time consuming/expensive to verify all data.

Question 8: Study close-out visits - objectives

Answer:

To bring closure to the study at a given site and to discuss with site personnel their continuing obligations.

Question 9: Study close-out visits - timing

Answer:

Ideally conducted after all data has been submitted and all queries resolved. Does not generally occur immediately after the last patient completes his/her study obligations; because all data should first be reviewed.

Question 10: Overview of the role of clinical data management

Answer:

To organize clinical trial data into a computerized database that completely and accurately reflects the findings and events of the trial.

Question 11: Study close out visits - CRA review w/ investigator

Answer:

The possibility of an audit (sponsor QA or the FDA). Grants/payment status (outstanding).Report/publications (as per sponsor SOPs and contract).Review investigator obligations: the investigator must send a final study report to the IRB and sponsor.This report should include the overall study status, a list of the SAEs that occurred at the site and a brief safety/efficacy summary [21 CFR 812.50 & 21 CFR 312.64] Reminder to file updated information to the financial disclosure forms if any information changes within one year of study completion

Question 12: Traditional source data process

Answer:

1.) patient visit source data 2.) Site completes case report form (CRF) 3.) CRA visits every 4-6 weeks 4.) CRF submitted to data management 5.) data entry generates discrepancies 6. clear CRF

Question 13: Study close-out visits - investigational product reconciliation

Answer:

The CRA should conduct a final accountability of study drug/device during the visit. The CRA should collect the following: all unused and returned medication/devices, or oversee destruction of the unused drug/device locally; all required documentation (copies of accountability logs, randomization envelopes/binding codes, etc.)

Question 14: Electronic Data Capture (EDC)

Answer:

This is the process of "paperless" CRF. A personal computer or laptop is installed at each investigative site; eCRFs may also reside on an internet server. Site personnel enter data into protocol-specific databases.

Question 15: Documentation of the visit

Answer:

As with all visits, the CRA provides a letter to the investigator after the visit to document activities, discussions and ongoing obligations. The CRA also completes a monitoring visit report, which is reviewed by sponsor personnel. Sample documents can be found in the workbook.

Question 16: Correcting CRFs during visit

Answer:

Coordinator availability: meet with the study coordinator at pre-arranged times to review the requested changes. Either side by side with the study coordinator or by leaving the requested changes with the study coordinator and rechecking the entires once all corrections have been made.

Question 17: Substantiating inclusion/exclusion criteria

Answer:

in most cases, the investigator is obliged to seek past medical history records from other physicians who may have treated a subj or who referred a subj to the investigator. The medical history taken when a subj enters the study should demonstrate that the subj meets all inclusion criteria. The investigator, not the sponsor, is responsible for the accuracy and completeness of his/her records, as well as any discrepancies found in these records during an inspection.

Question 18: Query flow process

Answer:

Queries are GENERATED after the original CRF data have been collected. Either the sponsor internally generates data queries (from data management, clinical or the medical monitor) or the CRA while at the research site generates data queries for the site. The CRC REVIEWS the queries to determine who is appropriate to answer the query. The query is ANSWERED by the site. The CRA or other sponsor representative source verifies the answered query. RE-QUERYING may occur. Once the sponsor determines the query has been answered appropriately the query is CLOSED.Question 19: CRA approaches to source verification - first review of course documents

Answer:

Read source documents "like a good book" flagging important areas such as AEs, identifying trends, etc. Match each CCRF to the source documents to make sure that all data has been entered, and vice versa. This method assures an unbiased review.

Question 20: Requesting data corrections

Answer:

Best practice: use of monitoring clarification form and "stickies" for identifying what areas have questions. Cons of only "stickies (in paper world): if queries aren't logged on a separate sheet, the stickies may get lost and the casebook will have to be re-monitored. A study coordinator can remove stickies prematurely once the corrections are done, leaving the CRA with nothing to crosscheck. The use of a clarification log prevents the problems listed above, however, query logs often take longer to write.