ACRP CCRC QUESTIONS AND ANSWERS Latest | 100% CORRECT

Audit Correct Answer: Reviews how the research was conducted; takes into account SOPs, IRB requirements & GCP (ensures compliance) Audit Certificate Correct Answer: Confirmation audit took place Audit Report Correct Answer: Written Evaluation - not regularly made available to regulatory body; only when serious evidence exists concerning non-compliance Audit Trail Correct Answer: Documentation of audit events Single Blind Study Correct Answer: Subjects Unaware Double Blind Study Correct Answer: Subjects & Researchers are unaware Comparator Correct Answer: Item used as an active control references in a clinical trail Coordinating Committee Correct Answer: Group a sponsor comprises to coordinate multi-center trials Coordinating Investigator Correct Answer: An investigator who oversees multiple sites of a clinical trial (multicenter) IDMC Correct Answer: Independent Data Monitoring Committee, Data & Safety Monitoring Board (DSMB), Data Monitoring Committee: Oversee safety & progress; make recommendations to continue, modify or stop IEC Correct Answer: Independent Ethics Committee; group who oversees protection, rights, safety & well-being of human subjects Investigator's Brochure Correct Answer: Compilation of data on an investigational product used in human subjects Legally acceptable representative Correct Answer: person whom is lawfully able to consent on behalf of another SAE Correct Answer: Serious Adverse Event - Results in death, is life-threatening, requires long-term hospitalization, results in long term disability/hospitalization incapacitation or is a congenital birth defect Source data Correct Answer: original clinical information from source documents (medical record information) Vulnerable subjects Correct Answer: *Hierarchical structure employees *armed forces *detainees *incurable disease pts *homeless *poor *those in nursing home *minors *those unable to give consent ICH Correct Answer: International Conference on Harmonization Principles of ICH & GCP Correct Answer: *Protect research subjects *conduct research as it has been approved *research should be clear, organized & approved by an IRB/IEC IRB / IEC Responsibilities Correct Answer: *Oversee principles of ICH/GCP *Make sure the PI / Co-Is are qualified * Review studies at least once a year Requirements of an IRB Correct Answer: * at least 5 members * one non-scientific member * one non-institute member What needs reported to the IRB? Correct Answer: *Changes / deviations from protocol due to unforeseen hazard * changes to subject risk * adverse events * new info that may impact subject safety Payment to subjects must be.... Correct Answer: prorated & not contingent on subject completing study Investigator Responsibilities Correct Answer: *Maintain delegation long *Ensure staff are trained/informed about the protocol (give delegated tasks) * Ascertain reason study participant withdraws consent while respecting their privacy & rights * Adhere to approved protocol *Document & explain any deviations from approved protocol * Process protocol amendments according to GCP *Manage proper storage & care for trial devices/drugs. (PI can delegate this task to trained professional - PharmD, etc) Protocol amendments should be submitted to Correct Answer: 1. IRB 2. Sponsor 3. Regulatory Authority Changes in risk to subjects... Correct Answer: should be included & approved on an updated ICF - patients enrolled should be re-consented Consenting illiterate subjects Correct Answer: is okay, but must have impartial witness present Necessary aspects of ICF Correct Answer: *Trial involves research *Trial purposes *Treatments - randomization aspect if applicable * Procedures *Subject responsibilities *Experimental Aspects of trial *Risks *Benefits *Alternatives to participating *Compensation * Compensation for trial related outcomes *Voluntary nature of trial *Who has access to direct records *Confidentiality of research records *New information will be made available to subject *Who to Contact *Involuntary termination *Trial Duration *Subjects to be enrolled Non-therapeutic trials can be conducted with consent from legal rep IF Correct Answer: *trial objectives cannot be met by personal subject consent *low risk *trial is not prohibited by law *IRB has approved such inclusion How long must documents be retained per GCP? Correct Answer: At least 2 years after last approved marketing application (organizations/sponsors, etc usually set a longer required period of 5-7 years) When to submit SAE to sponsor? Correct Answer: Immediately (usually within 24 hours) Sponsors role Correct Answer: *Complete & ensure SOPs are followed *seeks agreements from all parties *may use CRO to oversee; however, the sponsor is ultimately responsible CRO Correct Answer: Contract Research Organization Sponsor/Investigator agreement should contain Correct Answer: 1. Agreement to comply w/ GCP (adhere to protocol & IRB) 2. Agree to comply with data recording 3. Agree to permit monitoring 4. Agree to retain documents for specified length of time *Agreement should be signed by both parties Purpose of Trial monitoring Correct Answer: *Ensure rights & safety of subjects are protected *Report on accuracy of trial data *Ensure trial is compliant (protocol, GCP, etc) How is a monitor selected? Correct Answer: *Appointed by sponsor *Adequately trained & qualified *familiar with protocol, ICF, etc Responsibilities of monitor Correct Answer: *Main line of communication b/w investigator & sponsor *Verify investigator qualifications *Verify product *Verify product storage *Verify dosing & who is receiving it *Subjects receive direction on product use *Products are accounted for appropriately *Verify protocol is being followed *verify written consent on each subject *ensure investigator has investigator brochure *ensure all staff are informed about the trial *verify only eligible subjects are being enrolled *report recruitment rate *verify source documents (CRFs match) *patient withdrawal or missed visits are reported on CRFs *notify PI of any missing data or signed edits to data *monitor reporting of AEs *report on deviations Auditors vs Monitors vs inspectors Correct Answer: *Monitors - address data, storage of drug, & report to sponsor/investigator. They can be internal *Auditors - focused on compliance which is separate from routine monitoring - they should not be part of trial; independent committee reviewing data *Inspectors - IRB or regulatory body reviewing data Audit Plans Correct Answer: differ based upon study design, complexity, number of subjects on trial, etc Required essential documents provided before study opens Correct Answer: *IB *signed protocol & amendments *CRFS *ICF *ads to promote study *financial aspects of study *agreements (signed) *Approved by IRB study materials *Composition of IRB *Signed CVs of PIs *Storing & Handling of device/drug *shipping information *Emergency decoding procedures for blinded study *Master randomization list * Pre-trial monitoring report Required essential documents provided during study Correct Answer: *updates to IB *updates to protocol / CRF, etc *approvals from IRB of updated materials *updates to any procedures / tests / shipping *records of any monitoring visits *signed ICF *completed CRFs, signed & dated *documentation of edited CRFs *source docs for completing CRFs *documentation of AEs/SAEs *subjects screening log *Subject enrollment log *subject ID code list * investigational product accountability *signature sheet (KSP) *record of samples Required essential documents at completion of trial Correct Answer: *Investigational product accountability at site (ensures products were used appropriate ensures which products were used/returned *device construction list *ID code list *audit certificate *final monitoring report *decoding document returned *final report of trial by PI *clinical study report (interpret trial) Serious vs Severe events Correct Answer: Severe = degree of event (mild/moderate, etc) Serious = overall event outcome; dictates regulatory documentation & reporting Events that should be reported expeditiously Correct Answer: Events that are BOTH serious and unexpected (does not include events that are not study related, non-serious events and serious, but expected events) Reporting time frame for events Correct Answer: Fatal/Life threatening unexpected = ASAP; no more than 7 days after event Non fatal/Life threatening = 15 days *ok if not all info is available -- submit what you have Reporting for blinded studies Correct Answer: *when SAE occurs, it is generally suggested to break the blind for the patient unless *PI doesn't do this, the sponsor should *Blind should be maintained for research personnel, even if subject is told Phase I Trials Correct Answer: Human Pharmacology; assess safety & tolerability *usually non-therapeutic in nature *may use healthy volunteers unless its cancer *PKs & PDs 15-30 patients Goals: figure out if its safe and best administration Population: normal, healthy adults; if cancer -- end stage Phase II Trials Correct Answer: Therapeutic exploratory; explore medications - establish dose for phase III *begin to test drug therapeutically *Typically enrolls a very specific criteria on patients *may help lay groundwork for endpoints in phase III Fewer than 100 patients Goals: determines short term risks, examine preliminary effectiveness Population: controlled study with limited population Phase III Correct Answer: Therapeutic Confirmatory; confirm early findings; *establish efficacy *establish drug as beneficial to treat condition *set stage for marketing approval 100-1000's of patients Goals: confirm drug works, control & investigational group, double-blinded controlled studies Phase IV Correct Answer: Therapeutic use; outcomes of use, multiple endpoints, large trials *comes after drug approval (Think LINX PAS but for meds) *Basically confirms dosing, safety & effectiveness Note about Phase IV trials Correct Answer: Therapeutic use is never in phase I, II or II, but others can fall into continuum. Primary Variable Correct Answer: typically should only be 1 primary variable safety should be considered & sometimes can be included Secondary Variable Correct Answer: should relate to trial primary variable and be limited in number Global Variables Correct Answer: These assess the overall outcomes in objective terms. The PI may give impressions regarding the study Surrogate variable Correct Answer: kind of fill in for other variables and are pretty general Methods to avoid bias Correct Answer: blinding randomization Parallel Trial Design Correct Answer: Study Group ---------------- END Control Group -------------- END Crossover Trial Design Correct Answer: Study Group ---------- Control Group ------ END Control Group -------- Study Group ------ END *main issue is ample wash out time b/w crossovers Factorial Design Correct Answer: Evaluates two or more treatments simultaneously *Drug A *Drug B *Drug A & B *Neither Drug A or B Blood pressure Correct Answer: Systolic/Diastolic LFTs Correct Answer: Liver Function Tests Total Protein Albumin Bilirubin ALP (Alk Phos) AST/ALT Peak Correct Answer: Varies, but usually around 30 mins to several hours after dosing, depends on administration Kidney Function Correct Answer: BUN (urea nitrogen) Creatinine Nuremburg Code Correct Answer: The voluntary consent of the human subject is absolutely essential Date/time on ICF Correct Answer: only date is required; time is generally preferred by PIs A witness signature is required on ICF when Correct Answer: *using a non-English language short-form ICF *someone who can comprehend the language, but is unable to read, write, talk or who is blind *witness MUST be impartial Advocate Correct Answer: Is a witness assigned as a monitor to attest to consenting process Pre-Clinical Trials Correct Answer: Animal/Translational Research - 4.5 years Double Dummy Correct Answer: both groups of patients in a placebo controlled study take Who is ultimately responsible for staff training? Correct Answer: PI Can PI share study enrollment w/ PCP overseeing care? Correct Answer: yes, if subject agrees/consents Who gives IB to investigator? Correct Answer: sponsor Who gives IB to IRB? Correct Answer: investigator Does the PI need to notify sponsor of administrative changes to protocol, ICF, etc Correct Answer: No Who has responsibility for investigational product accountability? Correct Answer: PI/Site If unblinding occurs who reports & to whom? Correct Answer: PI to sponsor only LARs may sign for a subject if what conditions exist? Correct Answer: -non-therapeutic studies only -low risk to subject - cannot be conducted otherwise -IRB approves it -trial is not illegal by law Who reports change of risks to subjects & to whom? Correct Answer: PI to sponsor & IRB & site Who reports AEs & SAEs / to whom & in what order? Correct Answer: PI to 1. sponsor and then 2. IRB Premature trial termination should be reported using what schematic? Correct Answer: Termination Vortex Termination Vortex Correct Answer: PI ----- Subjects Below is a triangle of communication - two way streets with all parties PI ------ Sponsor PI ----- IRB IRB ------Sponsor Who creates SOPs Correct Answer: sponsor Who initiates and secures the agreement? Correct Answer: sponsor A CRO has been enlisted to oversee a study, who is primarily responsible for integrity of trial data? Correct Answer: sponsor Expedited reporting of AEs is necessary when what 2 things exist? Correct Answer: Serious & unexpected Who appoints a monitor? Correct Answer: sponsor Who acts as main point of contact b/w the PI & sponsor? Correct Answer: monitor Monitor should conduct monitoring visits according to what, created by whom? Correct Answer: SOPs / monitoring specifics, by the sponsor Audits differ from monitoring visits because Correct Answer: monitoring visits assess safety of subjects and day to day data collection & source documents. audits look for compliance with approved protocols Monitors & Auditors differ in what major way? Correct Answer: monitors are supplied by sponsor as part of sponsor team. Auditors are independent. An untoward event in a patient or clinical investigational subject administered a pharmaceutical product which does not necessarily have a causal relationship is what? Correct Answer: Adverse event an adverse drug reaction requires what level of causality? Correct Answer: reasonable possibility ADRs should be expeditiously reported when what two factors are present? Correct Answer: serious/unexpected fatal / life threatening ADRs should be submitted in what time frame? Correct Answer: no later than 7 days, but ASAP