INTRODUCTION TO CLINICAL TRIALS

1. PREPARED BY : AYSHA HUSSEIN

2. Clinical trials areconductedtoallow safety andefficacy data tobecollected for
health interventions (e.g.,drugs,diagnostics, devices, therapy protocols). These
trials cantake place onlyafter satisfactory information has beengathered onthe
quality ofthenon-clinical safety, andHealth Authority/Ethics Committee
approval is granted inthecountrywhere thetrial is taking place.
Dependingonthetypeofproduct andthestage ofits development, investigators
enroll healthy volunteers and/orpatients into small pilot studies initially, followed
bylarger scale studies inpatients that often compare thenewproductwith the
currently prescribed treatment. Aspositive safety andefficacy data aregathered,
thenumberofpatients is typically increased. Clinical trials canvaryinsize from a
single center inonecountryto multicenter trials in multiple countries.
CLINICAL TRIALS

3. clinical trial maybedesigned to:
1.Assess thesafety andeffectiveness ofa newmedication ordevice onaspecific
kind ofpatient (e.g., patients whohave beendiagnosed with Alzheimer's disease)
2.Assess thesafety andeffectiveness ofa different doseofamedication than is
commonly used (e.g.,10mgdoseinstead of5mgdose)
3.Assess thesafety andeffectiveness ofan already marketed medication or
device foranewindication, i.e.adisease forwhichthedrugis notspecifically
approved
CLINICAL TRIALS

4. clinical trial maybedesigned to:
4.Assess whether thenewmedication ordevice ismore effective forthe
patient's condition thanthealready used,standard medication ordevice ("the
goldstandard" or"standard therapy")
5.Comparetheeffectiveness in patients with aspecific disease oftwoormore
already approved orcommoninterventions forthat disease (e.g.,Device Avs.
Device B,Therapy Avs.Therapy B)
CLINICAL TRIALS

5. Clinical Protocol
AClinical TrialProtocolisadocument thatdescribes theobjective(s), design, methodology,
statistical considerations, andorganization ofaclinical trial.
Theprotocol usually alsogivesthebackground andreasonthetrialisbeing conducted, but
thesecould beprovided inother documents referenced intheprotocol (such asan
Investigator's Brochure).
Theformatandcontent ofclinical trialprotocols sponsored bypharmaceutical,
biotechnology ormedical device companies intheUnited States,European Union, orJapan
hasbeenstandardized: theyarewritten tofollow theGoodclinical practice guidance issued
bytheInternational Conference onHarmonization ofTechnical Requirements for
Registration ofPharmaceuticals forHuman Use(ICH). Regulatory authorities inCanada and
Australia alsofollow theICHguidance.
CLINICAL TRIALS

6. Statistical power
Thenumberofpatients enrolled inastudy hasalarge bearing ontheability of
thestudytoreliably detect thesize of theeffect ofthestudyintervention. This is
described as the"power"ofthetrial. Thelarger thesample size ornumberof
participants inthetrial, thegreater thestatistical power.
CLINICAL TRIALS

7. Clinical Trials phases
Clinical trials are conducted in a series of steps called “phases.” Each
phase has a different purpose and helps researchers answer different
questions.
Phase I trials: Researchers test a drug or treatment in a small group of
people (20–80) for the first time. The purpose is to study the drug or
treatment to learn about safety and identify side effects.
Phase II trials: The new drug or treatment is given to a larger group of
people (100–300) to determine its effectiveness and to further study its
safety.
Phase III trials: The new drug or treatment is given to large groups of
people (1,000–3,000) to confirm its effectiveness, monitor side effects,
compare it with standard or similar treatments, and collect information that
will allow the new drug or treatment to be used safely.
Phase IV trials: After a drug is approved by the FDA and made available to
the public, researchers track its safety in the general population, seeking
more information about a drug or treatment’s benefits, and optimal use.
CLINICAL TRIAL

8. Clinical Trial Design
1.Randomized Clinical trials
Arandomized controlled trial is thestudydesign that canprovide themost
compelling evidence that thestudy treatment causes theexpected effect on
human health.
Randomized
Eachstudy subject israndomly assigned to receive either thestudytreatment or
aplacebo.
Blind
Thesubjects involved inthestudydonotknowwhichstudytreatment they
receive. Ifthestudy isdouble-blind, theresearchers also donotknowwhich
treatment is being given to anygiven subject.
CLINICAL TRIALS

9. Clinical Trial Design
This 'blinding' is toprevent biases, since if aphysician knewwhich patient was
getting thestudytreatment andwhich patient wasgetting theplacebo, he/she
might betempted togive the(presumably helpful) studydrugtoapatient who
couldmoreeasily benefit fromit.
Inaddition, aphysician might give extra careto onlythepatients whoreceive the
placebos tocompensate fortheir ineffectiveness.
Placebo-controlled
Theuseofaplacebo(fake treatment) allows theresearchers toisolate theeffect
ofthestudytreatment.
CLINICAL TRIALS

10. Clinical Trial Design
2.Observational trials
Anobservational studydrawsinferences about thepossible effect ofatreatment
onsubjects, where theassignment ofsubjects into atreated groupversus a
control groupisoutside thecontrol oftheinvestigator.
This is incontrast with controlled experiments, such asrandomized controlled
trials, where each subject israndomly assigned to atreated grouporacontrol
groupbeforethestart ofthetreatment.
CLINICAL TRIALS

11. Clinical Trial Design
3.Metanalysis
-A meta-analysis combines theresults ofseveral studies that address aset of
related research hypotheses.
-Inits simplest form,this isnormally byidentification ofacommonmeasure of
effect size, forwhich aweighted average might betheoutputofameta-analyses.
-Here theweighting might berelated to sample sizes within theindividual
studies.
CLINICAL TRIALS

12. Clinical Trial Design
3.Meta-analysis
-Moregenerally there are otherdifferences between thestudies that need tobe
allowed for,butthegeneral aim ofameta-analysis istomorepowerfully
estimate thetrue "effect size" asopposed toa smaller "effect size" derived ina
single study underagiven single set ofassumptions andconditions.
-Meta-analyses areoften, butnotalways, important components ofa systematic
reviewprocedure.
CLINICAL TRIALS

13. Clinical Trial Design
4.Systematic Review
-Asystematic review is aliterature review focusedonaresearch question that
tries toidentify, appraise, select andsynthesize all highquality research evidence
relevant tothatquestion.
-Systematic reviews ofhigh-quality randomized controlled trials are crucial to
evidence-based medicine.
-Anunderstanding ofsystematic reviews andhowto implement themin practice
is becomingmandatory forall professionals involved inthedelivery ofhealth
care.
-Systematic reviews arenot limited to medicine andare quitecommon inother
sciences such aspsychology,educational research andsociology.
CLINICAL TRIALS