Clinical trial The Way We Make Progress Against Disease Prof. Ashry Gad Mohamed Prof. of Epidemiology College of Medicine & KKUH

Definition a clinical trial is defined as a planned experiment on humans. the setting is in health institutions environment and it usually involves patients. Rationale Before a new treatment method is made available to the public it must be studied and tested for safety and effectiveness.

Treatment Trials What new treatments can help people with a particular disease? What is the most effective treatment for people with that disease?

Basic terms in clinical trial Investigators Participants Intervention Outcome

Steps of clinical trial 1-Formulation of the hypothesis. Hormone replacement treatment (HRT) and Breast cancer. Trial of Vitamin D and calcium supplementation and hip fracture. Use of statins for the prevention of Myocardial Infarction. Use of the oral contraceptive pill and deep vein thrombosis (DVT).

2-Definition of Reference population. Experimental population. Necessary sample size. inclusion criteria. exclusion criteria.

3- Informed consent A process by which a subject voluntarily confirms his/her willingness to participate in a particular trial after having been informed of all aspects of the trial that are relevant the subjects decision to participate.

Protecting Patients’ Safety Informed Consent Before agreeing to take part, patients have the right to understand all that is involved in a clinical trial: Procedures and treatments Tests Possible risks and benefits

Protecting Patients’ Safety Institutional Review Board Committee made up of experts

4-Allocation of regimens Intervention versus Placebo Current treatment Nothing Randomization Aim Methods

Variants of clinical trials: 1-Parallel design: Parallel groups design: each patient receives only one treatment. Follow up Ref. Pop. Sample Intervention Control OUTCOMEOUTCOME

Clinical trial & number of participants 1-Mega Trial Thousands of patients Multiple centers Statistical power Generalization 2-Sequential trial No specified sample size Continuous recruitment Clear benefit / no difference

3- Fixed size trial Most common Study power 4- N of one Every physician Routine work

Blinding One or more of the people involved in the trial is unaware of the intervention. 1- Open trial 2- Single- blind trial 3- Double blind trial 4-Double blind double dummy trial 5- Triple and quadruple blind

Collection of baseline data Disease, medical & demographic characteristics. Similarity in all aspect except intervention. Follow up Quantity Quality Compliance

Outcome Objective Vs subjective. Surrogate Vs hard outcome.

Analysis Intension to treat analysis. 15/ 60 =0.25 =25% Protocol analysis. 15/45 = 0.33 =33%

Relative Risk TotaloutcomeGroup Negativepositive a +bbaIntervention c +ddcControl

Measures of effect size 1-Relative risk (RR) – Is the ratio of the risk of a given event in one group of subjects compared to another group Experimental Event Rate (EER) Control Event Rate (CER ) EER: The percentage of intervention group who experienced outcome in question. ( a/(a + b)) CER: The percentage of control group who experienced outcome in question. (c /( c + d))

RR=(18/64) / (29/65) = 0.281/0.446 =0.63 =63% 95% CI= 0.39 – 1.01 Source: N Engl J Med 1992; 326: InterventionOutcomeTotal Deathsurvival Ligation sclerotherapy293665