PHASES OF CT Flashcards
what do you need to do before CT?
sponsor must file an IND with the FDA
- IND must include results from pre-clinical studies
- must wait 30 days before starting studies in human
- INDs must be updated manually
what is the purpose of phase 1?
first-in-human study purpose :
- to determine the metabolic and pharmacologic action (ADME) of the drug in humans
- asses the adverse effects associated with different doses
- get an indication of the efficacy of the IP
- PRIMARY CONCERN : safety and not efficacy of IP
- permit designing safe, well-controlled, sceintifically sound phase 2?
characteristics of phase 1?
- short duration
- small group of healthy volunteers
- very closely monitored
- not randomized ; everybody receives the active compound
- often done in special testing facilities
what is randomisation?
The process of assigning trial subjects to treatment or control groups using an element of chance to determine the assignments in order to reduce bias
- include control group and treatment groupS
what is stratification?
Categorizing subjects into subgroups by
specific characteristics
what is the purpose of Phase 2?
- To determine whether or not the IP demonstrates efficacy for the indication within the safe dose range established in phase I
- asses the risks and short term adverse effects
- safety will still be the primary concern
PHASE IIA : asses dosing requirements
PHASE IIB : study efficacy - dose ranging finding ; establish a min and max effective dose
characteristics of Phase 2?
- rigid and well-controlled studies
- small patient population ; less than a few hundreds
- subjects have the targeted disease but no other illnesses
- consists of double-blind studies using a placebo or comparator drug or both
what is binding?
aka masking :
A procedure in which one or more parties to the
trial are kept unaware of the treatment
assignment
SINGLE-BLIND : Subjects being unaware of the treatment assignment
DOUBLE-BLIND : subjects, invs, monitor/CRA being unaware of the assignments
what is control?
used as a reference aka comparator
- Active compound : another market drug or diff dose of drug under the study
Placebo : A preparation which is pharmacologically inert but do not have any therapeutic effect
when does phase 3 starts?
data generated in phase 1 and 2 must show satisfactory safety profile and have sufficient evidence of efficacy
what is the purpose of phase 3?
- demonstrate the long-term safety and efficacy needed to assess the risk/benefit relationship of the drug and to provide adequate data for the product package insert
- compare new treatment against standard
treatment
characteristics of phase 3?
- expanded, randomized, controlled studies
- large patient populations
- The patient population represent the types of patients the compound is intended to treat after it is marketed
- may extend to several years
Phase 3a?
Phase 3a : conducted after efficacy of the drug
is demonstrated but prior to regulatory
submission
- patients with targeted disease
- generate additional safety and efficacy data
- may conduct in special patient groups
- provide info needed for the package insert and labelling of the medicine
Phase 3b?
conducted after regulatory submission but before approval and launch of drugs
- gather additional safety data, additional indications for the drug or to assess it’s use in special patient populations
when does phase 4 starts?
Done after the approval of NDA (Post-Marketing Trial)
- to determine additional information about the safety or efficacy profile of the compound
what is included in phase 4?
- studies required as a condition of approval by the FDA
- long term safety studies required by FDA
- studies comparing ip with other marketed drugs
- studies designed to familiarise physician with the compound
- provide further detail about the medicine’s efficacy and safety profile
- diff formulations, dosages, duration of treatment and drug interaction may be evaluated
what happens if a marketed medicine is to be evaluated for a new indication?
trials will be considered phase 2 trials
key things?
- Phase I studies are small safety studies, usually done in healthy volunteers
- Phase II studies are usually the first studies in patients with the disease or condition of interest
- Phase III studies are large, comprehensive safety and efficacy trials
- Phase IIIB studies are those being done during the time the compound is in the FDA review cycle
- Phase IV studies are done after approval of approval of the compound
what is randomized control trials?
Are comparative studies with an intervention group and a control group
- most rigorous way of determining whether cause-effect relation exists and the cost effectiveness of a treatment
advantages of RCT?
- removes the potential of bias in the allocation of participants to the intervention group or control group
- the variables and other characteristics of the participants will be evenly balanced between the intervention and control group
- Validity of statistical tests of significance is
guaranteed
impt features in RCT?
- random allocation to intervention groups
- All intervention groups are treated identically except for the experimental treatment
- Patients and trialists should remain unaware of which treatment was given until the study is completed
attributes of a proper randomisation scheme?
- Assignment remains unknown to the patient, doctor and the clinic staff until it is needed for treatment initiation
- future assignments cannot be predicted from past assignment
- order of allocation is reproducible
- method of generation is documented
- method of generations provides clear audit tracking
disadvantages of RCT?
- limited by ethical and practical concerns
- more costly and time consuming
