Clinical Trials

What are the 8 elements of informed consent?

1. Purpose of the research, duration of participation, description of procedures 2. Foreseeable risks or discomforts 3. Benefits to the subject 4. Alternative procedures or courses of treatment, if any 5. Extent to which confidentiality of records will be maintained 6. Research involving more than minimal risk - any compensation & medical treatments available if injury occurs 7. Who to contact with questions about research & rights, & who to contact in event of a research related injury 8. Statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which subject is entitled, & that the subject may discontinue participation any time without penalty or loss of benefits to which subject is entitled.

How long should a sponsor wait for the Investigational New Drug (IND) Application from the FDA?

30 days

What key dates must be observed on clinicaltrials.gov?

Clinical trial must be registered in clinicaltrials.gov; register within 21 calendar days after enrollment of first patient; results must be reported no later than 1 yr. after the trial's primary completion date.

What is the definition of a Clinical Trial?

Clinical trial: research study in which one or more human subjects are assigned to one or more interventions to evaluate effects on health related biomedical or behavioral outcomes.

Name the web-based resource that provides patients, their family members, health care professionals, researchers, & the public with easy access to info on publicly & privately supported clinical studies on a wide range of diseases & conditions.

Clinicaltrials.gov

Whose responsibility is it to manage the clinicaltrials.gov profile?

If the sponsor of the clinical trial is industry, the onus falls on sponsor to manage clinicaltrials.gov profile; Otherwise, PI would have to manage it if it's an investigator initiated study where PI owns the IP of the study.

What form must be completed to the FDA for a significant risk device study?

Investigational Device Exception (IDE)

What are the means through which the sponsor obtains exemption from FDA to ship a drug to clinical investigators in many states.

Investigational New Drug (IND) Application

What indicates approval of an Investigational New Drug (IND) Application from the FDA?

No response indicates approval

Describe the four phases of a clinical trial

Phase 1 - First in human study; healthy volunteers (usually 20-80 people); short duration of time; determine safety; how drug moves through the body (pharmacokinetics). Phase 2 - randomized, placebo controlled study in patients with disease or condition (several hundred people); longer study & more patients; establish dose range that yields efficacy; safety & side effect profile. Phase 3 - large randomized (several hundred to several thousand people), placebo controlled trial across multiple clinical sites for an extended period of time; generally double blinded (neither the participants nor the experimenters know who is receiving a particular treatment); performed to demonstrate that a statistically significant effect for a primary endpoint can be determined; provides data to gain regulatory approval for intended indication. NIH phase 3 aim is to provide scientific evidence that would support a change in health policy or standard of care. Phase 4 - drug has been approved by the FDA; post marketing studies; may be voluntarily conducted by company or mandated by a regulatory agency; used to explore new indications; increase safety & side effect database; monitor effectiveness & adverse effects in general population.

What are the steps of protocol design in a clinical trial?

a. Establish primary outcome (study design & execution) b. Draft an informed consent form (ICF) c. Establish inclusion & exclusion criteria d. Determine feasibility & budget e. Secure clearance to access protected human info f. Establish data management work stream g. Complete necessary education requirements for your institution

Who regulates clinical trials?

a. FDA - adherence to principles of good clinical practices (GCPs), including adequate human subject protection (HSP). b. Office of Human Research Protections (OHRP) - provides leadership in protection of the rights, welfare, & wellbeing of human subjects involved in research conducted or sponsored by DHHS. c. Sponsor - may require additional regulatory requirements for sites conducting clinical trials & often have separate requirements for reporting subject data & adverse event info.

What are the basic steps of a clinical trial?

a. Recruiting & screening - when informed consent is obtained. b. Baseline visit c. Randomization - coin toss for what patient is receiving. d. Intervention(s) - when they receive the treatment, device, etc. e. Follow up visits f. Data collection g. Adverse event tracking - PI will try to determine if study drug is causing the adverse event. h. Data lock & study completion

What constitutes research misconduct in a clinical trial?

fabrication, falsification, and/or plagiarism

What needs to be demonstrated in an Investigational Device Exception (IDE)?

must demonstrate that anticipated benefits outweigh risks to human subjects & that there is reason to believe device as proposed for use will be effective.

Describe the hallmarks of Good Clinical Practice (GCP)

protect the rights, safety, & wellbeing of human participants; assure quality, reliability & integrity of data collected; provide standards & guidelines for the conduct of clinical research.

Briefly describe what is involved in informed consent

provide adequate info to allow informed decision & obtain voluntary agreement to participate (voluntary, comprehension, & disclosure/benefits). Explains the study to patients, risks & benefits, that the study is voluntary, & can withdraw participation at any time.

What are the roles of the Clinical Research Coordinator (or Study coordinator)?

recruits study subjects; explains research study & obtains informed consent; oversees the study visits; monitors patient well-being; records adverse events; may dispense, track, or store study material; & manages day to day aspects of the study.

What is the definition of Clinical Research?

research conducted with human subjects in which an investigator or other personnel directly interact with human subjects or on material of human origin (e.g. tissues & biospecimens).

Outline the Significant Risk process for a clinical trial

sponsor submits IDE application to FDA; FDA approves, approves with conditions, or disapproves the IDE within 30 days; sponsor obtains IRB approval; investigation may begin after both the FDA & IRB approvals are in place.

Outline the Non-significant risk process for a clinical trial

sponsor submits to IRB including a statement of why an NSR classification is requested; if IRB approves as NSR then investigation may begin; abbreviated IDE requirements are handled locally with no IDE submission to FDA needed.