DD 05 Exam 41 Questions with Answer Latest
Phase 2 Studies - CORRECT ANSWER Conducted to gather preliminary efficacy data and additional safety
... [Show More] data. Primary goal of phase 2 is to identify the therapies that warrant further investigation based on acceptable toxicity and efficacy. They provide additional safety data, refine research questions, develop research methods, and design phase 3 research protocols. Phase 2 studies are often controlled (placebo controlled). Phase 2 studies evaluate efficacy of a drug for a specific indication (no more than several hundred sick people). Phase 2 studies may reveal short-term side effects and risks. The length of phase 2 studies varies from months to 2 years. Note: only 33% of phase 2 drugs make it to phase 3.
Phase 2 Study Design - CORRECT ANSWER Uses the dose and method found safest and most efficacious in phase 1 studies. Randomized controlled trials are the preferred method, where comparison allows optimization of dose and the study is controlled by a placebo. Note: noncomparative studies are not-preferred unless there is a compelling reason not to use a placebo control (deadly disease).
Phase 2 Single-Stage Design - CORRECT ANSWER Simplest method. Defined sample number of patients who all receive the same dose or a placebo control. Outcomes are then assessed after completion. Allows assessment of response rate with precision. The weakness of a single-stage phase 2 design is that it may expose sick patients to inferior or toxic therapies. Note: phase 2 single stage design is best used for rapidly accruing studies.
Phase 2 Multi-Stage Study - CORRECT ANSWER Uses 2 stages. Stage 1 involves a minimal efficacy that must be achieved to proceed to stage 2. If patients don't reach the desired efficacy, the study is discontinued. If patients however reach the desired efficacy, stage 2 can be started. Stage 2 enrolls more patients. This is advantageous because it allows for early termination of the study if toxicity/lack of efficacy is found. The drawback in multi-stage studies is that it may cause numerous study suspensions and reassessment - prolonging the study.
Phase 2 Study Randomized Control Trial - CORRECT ANSWER Method involves an active drug and placebo control. Randomized with stratification. Uses multiple arms of the study (with multiple doses) where patients are randomly assigned. If one arm fails, discontinue that arm and reassign patients to a different arm. The successful arm(s) are selected for further analysis. Note: unlike phase 3, randomized control studies are not powered to determine true clinical improvement, only to reinforce potential efficacy data and warrant further study (phase 3).
Phase 2a / 2b Study - CORRECT ANSWER Don't refer to study designs but rather a stage of phase 2 trials. Refer to early and late phase 2 studies. Phase 2a refers to the pilot clinical trial to evaluate efficacy and safety. Phase 2b refers to late phase 2 clinical trials where the scale is smaller and more closely resembles a phase 3 study.
Phase 2/3 Study Design - CORRECT ANSWER Randomized controlled trials. Efficacy without notable toxicity permits full advancement to phase 3 trials. Allows phase 2 data to be published in final analysis. Tends to shorten the time of trial completion and decreases the number of required patients. Note: requires additional preplanning in that both phase 2 and phase 3 portions are designed simultaneously.
General Phase 2 Study Design Principles - CORRECT ANSWER Define biomarkers predictive of efficacy or toxicity. Predefine the study population (who is being treated). Larger phase 2 studies may be powered to detect an effect in a trial population. Adaptations commonly seen in phase 2 studies as they are progressing include: stopping early, continuing longer than expected, dropping/adding arms, focusing on patient subsets. Note: adaptations are far less allowable in stage 3 studies.
Phase 2 Study Endpoints - CORRECT ANSWER Looking for specific endpoints to evaluate efficacy (clinical importance). Choice of the primary endpoint is critical in the design of phase 2 studies. Phase 2 is tailored to the disease and drug under investigation. Common endpoints include: response rate (cure, tumor response, etc), subjective measures (pain, improvement, etc), surrogate markers / biomarkers, and time to event analysis (exacerbation or hospitalization). Note: FDA must be consulted to see if the endpoints will support approval.
Phase 2 Patient Selection Criteria - CORRECT ANSWER Define a specific patient population using inclusion and inclusion criteria that the drug is most likely to work in. Define the disease in this population that the drug is supposed to work in. Assess disease severity. Note: it is important to be specific in patient selection to ease phase 3 trials but not too specific to exclude too many patients.
Phase 2 Statistics - CORRECT ANSWER Statistics are required in phase 2 (as opposed to phase 1). Sample size must be adequate. Number enrolled and analyzed must be defined. Type of analysis must be defined (intent to treat, etc). Expected results must also be defined ahead of time. Must also include stopping rules.
clinicaltrials.gov - CORRECT ANSWER FDA repository and registry of all clinical trials. Includes phase 1 only if they are studying efficacy. All phase 2 and phase 3 are included on clinicaltrials.gov (with some phase 1). Note: all studies used to support an application for a new drug or new indication must be submitted to this registry prior to study initiation.
Clinical Hold - CORRECT ANSWER Order issued by FDA to sponsor of IND application to delay or stop the trial. Can happen at any time in any phase. Prevents the trial from proceeding until the FDA lifts the hold. Phase 1 holds can be caused by unreasonable risk/injury, investigators are unqualified to do the trial (training/education), erroneous or misleading information in the IND, or IND does not have complete risk information. Phase 2 and 3 holds can be caused by any condition that would cause a phase 1 hold and/or plan/protocols of the study are clearly deficient in meeting stated objectives.
Reasons for Clinical Holds - CORRECT ANSWER Product quality (impurities cause health hazards, product not stable throughout testing program), pharmacology/toxicology (data from animals insufficient to warrant human exposure or poor toxicology studies with a poor safety marker), or clinical (previously observed toxicity of the product has not been addressed in the protocol, unpredictable acute toxicity protocol not executed properly - patients should have staggered administration to look for toxicity rather than just giving it to all patients at once).
Expedited Programs - CORRECT ANSWER FDA programs to expedite drug approval, especially for new drugs that address an unmet medical need. More common recently than in the past. For example, of the 22 drugs approved by the FDA, 36% were fast-tracked and 32% were breakthrough. 68% of drugs approved in 2016 had some sort of priority review by the FDA.
Fast-Track Designation - CORRECT ANSWER FDA special treatment. Can submitted for and possibly granted any time after IND approval through phase 2 studies. Provides advantaged to manufacturer that can speed the development process. Can include more FDA meetings, accelerated approval (uses only a surrogate or biomarker to show efficacy), priority 6 month review, or a rolling review (allows for submission of approval as the study is progressing). A drug is eligible for fast track only if it meets an unmet need, shows superior efficacy/toxicity to other available agents if applicable.
Qualified Infectious Disease Product - CORRECT ANSWER "QIDP". Special type of fast track designation that adds 5 years of market exclusivity. Qualified if submitted to FDA and meets qualifications for fast-track designation.
Breakthrough Therapy Designation - CORRECT ANSWER Can be granted by FDA any time after IND. Used for products that are believed to cause a substantial improvement over other therapies for life-threatening conditions. Can be granted with only preliminary studies (even animal studies). Recieves all the same advantages of a fast-track designation, however drug development process guidance by the FDA is more personalized.
Drug Naming - CORRECT ANSWER During preclinical studies, the drug is often identified by their chemical/code name. Phase 1 is often also using the chemical/code name. Phase 2 or 3 starts the process for developing a generic and brand name.
Code Name - CORRECT ANSWER Internal name given to a drug by manufacturer. Often has some sort of initials of the manufacturer combined with the chemical designation.
Chemical Name - CORRECT ANSWER Early studies generally only use the chemical IUPAC designation of the chemical. Can be later code named by the manufacturer.
Generic Name - CORRECT ANSWER Nonproprietary name given to the drug during phase 2 or 3 trials
Brand Name - CORRECT ANSWER Name that is picked by the manufacturer any time they want during the development process. Often trademarked ahead of time with the US Patents and Trademarks Office. Even though the manufacturer assigns the brand name, the FDA reserves the right for final approval of that name.
USAN - CORRECT ANSWER United States Adoptive Name counsel. Governing body that assigns generic names. In order to get a generic name, the drug must have gone through IND and approved. Generally USAN application occurs in phase 1 or phase 2, and is generally approved in phase 3. The USAN is responsible for coining the names for new drugs, but the manufacturer can submit desired names. Rules: Must include the "stem" that denotes the pharmacology of the drug. Certain letters are avoided in new drug names.
OPDP - CORRECT ANSWER Office of prescription drug promotion. Department within the FDA. Reviews the brand name of a drug to determine if the name implies some sort of efficacy, minimize risks, or make some sort of other implication on indications or superiority. "prevents names like cancerkill".
DMEPA - CORRECT ANSWER Division of medication error prevention analysis. Department within the FDA. Searches drug databases, computational methods, or prescription simulator studies to determine if a drug name will be confusing. Compares the drug name to existing drugs to help prevent mistakes in look/alike - sound/alike. Scrutinizes spelling, appearance, pronunciation, etc.
Phase 3 Studies - CORRECT ANSWER Primary goal is to assess the efficacy and safety of a drug and its value in a desired population. Confirms preliminary evidence accumulated in phase 2 that a drug is safe and efficacious in a recipient population. Provides and adequate basis for potential market approval.
Phase 3 Study Characteristics - CORRECT ANSWER Randomized, controlled, multiple arm trials. Enrolls a large number of patients (hundreds to thousands). Assesses the drug effectiveness in comparison to placebo or current "gold standard" drug. Most expensive and time consuming trial to conduct.
Phase 3a Trial - CORRECT ANSWER Conducted after efficacy of the medicine is demonstrated, but prior to the NDA. Generates additional safety/efficacy data on a large number of patients or special subgroups of patients.
Phase 3b Trial - CORRECT ANSWER Conducted after NDA submission but prior to official approval and launch.
Study Randomization - CORRECT ANSWER Process in which eligible study subjects are randomly allocated to receive one of several predetermined interventions such as placebo, drug, or other drug. Randomization eliminates bias, stratification of recruitment (such as patient risk factors), and enabling a blinded study.
Phase 3 Study Objectives / Outcomes - CORRECT ANSWER The medical questions that need to be answered should be clearly formulated so the necessary resources can be applied such as: number of subjects, study duration, endpoint evaluations, facility/equipment, personnel. Includes primary outcome measures and secondary outcome measures.
LEADER Study - CORRECT ANSWER Primary outcome: time from randomization to first occurrence of cardiovascular death, non-fatal MI, or non-fatal stroke. Secondary outcome: time from randomization to expanded composite cardiovascular events.
Phase 3 Participant Selection - CORRECT ANSWER Defined patient population using inclusion and exclusion principles. Disease must be clearly defined and the disease status (severity).
Phase 3 Statistics - CORRECT ANSWER Very important in phase 3. Uses a power requirement for results. Number of participants must be specified. Type of analysis must be done (intent to treat, etc). Dropouts or withdrawal of consent. Expected results.
IRB - CORRECT ANSWER Institutional Review Board. A committee of physicians, statisticians, researchers, and community advocates. Ensure the clinical trial is safe, ethical, and that the rights of participants are protected. All clinical trials in the US must be approved from an accredited IRB prior to initiation. IRB reviews all consent forms and ensures they are complete (provides a seal of approval). Note: every institution that conducts or supports research involving human participants must have an active IRB that initially approved and periodically reviews research to protect participants rights.
CITI Training - CORRECT ANSWER Certificate training program for basic biological safety and studies. Involves ethics modules and good lab practices, etc. Required for involvement in clinical research.
NDA - CORRECT ANSWER New Drug Application. Application submitted by the sponsor to the FDA after the requisite clinical trials have been completed. Provides a license to market the drug for a specific indication. Goals of the NDA are to provide the FDA with enough information to allow marketing to the public. Questions that should be answered by phase 3 include: is the drug safe and effective in the proposed use? Do the benefits outweigh the risks? Is the drug label comprehensive? Are the manufacturing methods appropriate and quality? FDA may refuse a NDA and ask for more data before reevaluating an NDA.
CDM - CORRECT ANSWER Clinical Data Management. CDM is needed to ensure validity, quality, and integrity of data obtained from trial subjects in phase 3. Involves case report forms (CRF), databases, data entry, quality assurance, and archiving. Is a continuum process where protocols are completed and entered on a CRF. The CRF is then added to an electronic database that is later reviewed. Reviewed databases may then be analyzed, then locked.
Protocol Deviation - CORRECT ANSWER Some occurence happens during the trial that violates the protocol. Must be reported to the sponsor to see if they want to accept that data or not. Must also involved the IRB so that all the circumstances of the deviation are looked at.
Phase 3 Facility - CORRECT ANSWER Site feasibility assessment is done in accordance with the sponsor and IRB. Equipment, data management plans, and source documents are done. Training and education of investigators is done. Storage of IP must be appropriate and documented. Participant screening, consent, and questioning must be appropriate. Contingency plans for deviations must be in place. [Show Less]