# 1st lect 1 intro to interventional research
- 1. Dr. Eman M. Mortada Professor In public health and preventive medicine Introduction To intervention research A Real World Application of the Scientific Method
- 2. Define basic concepts Revise Hierarchy of evidence and different designs Identify components of The Classical Experiment Characteristics of experimental research Enumerate Types Of Clinical Trials List The major ethical principals in clinical trials Lecture Outline
- 4. Virtually every medical treatment available to human use, from drugs, devices, surgical procedures to diagnostic technology, stems from a single source: Research Medical Treatment Why do we need clinical trials?
- 5. How do you know if the medicines you take are safe? All medical drugs, treatments, preventions and even medical devices have to go through a process before they are available to you This process is called a Clinical Trial. Dr. Eman Mortada http://publichealth.columbus.gov/uploadedImages/Public_Health/Cont ent_Editors/Infectious_Diseases/Immunizations/preschooler%20getting %20a%20shot.JPG
- 6. I have discovered a new drug My objective now is to market it to gain money ☺ Dr. Eman Mortada
- 7. ☺ But the FDA will not let you do so What is the FDA??????????????????????? why??????????????????????? Dr. Eman Mortada
- 8. FDA (Food and Drug Administration) FDA is the main consumer watchdog for numerous products: Drugs and biologics (prescription and over-the counter) Food Medical devices Animal feed and drugs Cosmetics Radiation-emitting products (such as cell phones and pagers) Dr. Eman Mortada
- 9. ☺ Because the FDA is not sure If your drug is safe and effective Dr. Eman Mortada
- 10. ☺ How can I convince them that the drug is safe and effective? By bringing evidence through clinical trials Dr. Eman Mortada
- 11. Hierarchy of evidence from clinical research 2nd
- 13. Hypothetical example A researcher tried jalapenos on a stomach ulcer patient, and the ulcer went away. The researcher published an article: “Jalapenos Cure Stomach Ulcers.” The next patient subjected to the same treatment died. The researcher published a follow-up article: “More Detailed Study Reveals That Jalapenos Cures 50% of Stomach Ulcers.”
- 14. Research is a collection of methodology used systematically to produce knowledge about something. What is research? Definition
- 15. Research design It can be defined as a blue print of research study, which enables the researcher to know: ❖ what, ❖ when, ❖ where, ❖ on whom, ❖ and how the study will be conducted. Definition
- 16. Types of research deigns Several different study designs are used in epidemiology. Each research design is suited for different objectives and purposes, and each has its own advantages and disadvantages. There are 2 main categories of research methods: Descriptive or analytic Dr/ Eman Mortada
- 17. Is there a comparison group? Descriptive studies Analytical studies Does investigator intervene? Observational study Experimental study YES NO NO YES Study Designs
- 19. Types of Descriptive studies Population Ecological Individuals Cross sectional Case report Case series
- 21. Definition Experimental research design According to Riley, experimental research design is a Best research methodology & powerful design for testing hypotheses of causal relationship among variables.
- 23. The Classical Experiment Experiments involve: Taking action Observing consequences of that action Major Components 1. Independent and Dependent Variables 2. Experimental and Control Groups 3. Pre-testing and Post-testing IV DV Experimen tal group Control group Pretesting posttesting
- 24. Independent Variables Dependent Variables This variable is manipulated (controlled) by the experimenter Known factor “The Cause” Treatment or intervention 1.Independent vs dependent Variables Does I.V. → D.V.???? This variable is measured” is used to determine the effect of the independent variable Unknown factor “The outcomes ” Responses or Endpoints
- 25. Independent Variable “The Cause” Dependent Variable “The Effect” Experimental or Treatment Variable Criterion or Outcome Variable Independent Variable influences the dependent Variable
- 26. Dr/ Eman Mortada
- 27. e.g. A randomized trial of breast cancer risk counseling: the impact on self-reported mammography use. What is the IV & DV in this study? ❖ IV is type of counseling (with 2 or more levels, risk counseling and no counseling or standard care). ❖ DV is self-reported mammography use.
- 28. A study conducted to assess Impact of smoking status on long-term mortality in patients with acute myocardial infarction What is the IV & DV in this study? • IV is smoking status. • DV would be long-term mortality.
- 29. 2. Experimental vs Control Groups • Experimental group: receives treatment • Control group: does not receive treatment
- 30. 3. Pretesting vs Posttesting ❑ Subjects are initially measured in terms of the Dependent Variable prior to association with the Independent Variable (pretested) ❑ Then, they are exposed to the Independent Variable ❑ Then, they are re-measured in terms of the Dependent Variable (posttested) ❑ Differences noted between the measurements on the Dependent Variable are attributed to influence of the Independent Variable Pretest Posttest
- 31. Notation for experimental designs X = Exposure of a group to an experimental treatment ❖ X1=treatment group ❖ X0=control/comparison group (no treatment) O=Observation or measurement of the dependent variable (pretest, posttest, etc.) ❖ O1= pre-test (measurement) ❖ O2= post-test (measurement) X is An independent variable & may be a: A particular medication A particular exercise regimen O is the Observation, that is, the measure for the dependent variable The researchers are looking to see if these measures change because of the treatment Details are on the 8th lecture R =Random assignment to the treatment or the comparison group
- 34. •Subjects are randomly assigned to groups. •Random assignment: -individual participants have the chance of being assigned to any of the two groups -eliminates extraneous variables Randomization
- 35. True Experimental Research Quasi-experimentalResearch Pre-experimental Research Types Of Experimental Research Details are on the 8th lecture
- 36. Types of experimental Designs Randomized or True experiment Yes No Is random assignment used? Is there a control group or multiple measures? Yes No Quasi-experiment Pre-experiment Details are on the 8th lecture
- 37. Dr: Eman Mortada Community trials The community is the unit of study Field trials Healthy people are the unit of study Clinical trials Patients are the unit of study Types of Experimental Studies Depending on Unit of Study Details are on the 2nd lecture
- 38. 1- assess a new line of treatment (a new drug for example) In a study of the treatment of acute diarrhea, children with acute diarrhea were randomly allocated to receive either rice- based oral-rehydration fluid or the standard treatment (glucose-based oral rehydration fluid). The average duration of the diarrhea in each group was then compared between the two groups.
- 39. 2- to compare two types of treatments: surgical or medical A study that evaluate two treatments for breast cancer. Women with stage 1 breast cancer are randomized to receive to 2 groups, one treated surgically only and the 2nd group treated both surgically and take doses of radiotherapy. Women are followed for 5 years to determine if there are any differences in breast cancer recurrence and survival.
- 40. It is usually used to: 1- assess a new line of treatment (a new drug for example) or 2- to compare two types of treatments: surgical or medical Dr: Eman Mortada Clinical trials ❑ Clinical trials have the objective of finding the best intervention to prevent, and treat diseases Clinical trials are ”Gold standard” in epidemiological research & the best epidemiological study design to prove causation.
- 41. Randomized Trial Design Time Defined Population New Treatment Current Treatment Improved Not Improved Improved Not Improved R A N D O M I Z E D
- 42. Core Components of Clinical Trials Involve human subjects Move forward in time Most have a comparison CONTROL group Must have method to measure intervention Focus on unknowns: effect of medication Must be done before medication is part of standard of care Conducted early in the development of therapies
- 43. Clinical Trial Phases Phase I trials Phase II trials Phase III trials Phase IV trials Phase 1: Healthy volunteers Phase 2: Focus on efficacy Still Evaluating safety Phase 3: Effectiveness trials Mostly RCTs Phase 4: Post marketing Monitor possible adverse events Traditionally, clinical trials of new therapies or devices pass through the following phases: Details are on the 2nd lecture
- 44. Trials are useful for evaluating: New drug or other treatment for disease New medical/health care technology Methods of prevention Methods of health promotion Programs for screening and diagnosis Methods of providing health care New health care policies Randomized trials are ideal design to evaluate effectiveness and side effects of new forms of intervention
- 45. Types Of Clinical Trials Lecture Outline
- 46. Treatment Trial Preventive Trials ScreeningTrial Diagnostic Trials Quality of life trials Types Of Clinical Trials Based On Purpose and uses of the trial: Details are on the 2nd lecture
- 47. Types Of Clinical Trials Based On =According to the Number of Participants: N-of-one trials: with only one participant Megatrials: 1000+ patients, worldwide, multicenter Sequential trials: Number of participants is not specified Fixed trials: Pre-defined sample size
- 48. Types Of Clinical Trials Based On Number of participating centres: Single centre vs Multicentre • A Multicenter research trial is a clinical trial conducted at more than one medical center or clinic. • Reasons for Multi-center Trials : 1. To recruit necessary number of subjects within a reasonable time. 2. May assure a more representative sample of the study or target population 3. Enables investigators with similar interest and skills to work together on a common problem
- 49. Types Of Clinical Trials Based On Randomization Randomized controlled trials Non Randomized controlled trials Simple Randomization BlockedRandomization Stratified Randomization Cluster Randomization Types Of Randomization Details are on the 5th lecture
- 50. Types Of Clinical Trials Based On Presence of Control group: Controlled trials: Concurrent Control Historical control Uncontrolled/ Open: The same group / individual is compared before and after treatment/ vaccination 1. Uncontrolled/ Open: The same group / individual is compared before and after treatment/ vaccination. 1. Controlled trials: Treatment and Control groups are always there. • Concurrent Control • Historical control Details are on the 5th lecture
- 51. Types Of Clinical Trials Based on Blinding (Masking): Open label or non- blinded trial: Everyone involved in trial knows Single blind trials: Blinding of patients Double blind trails: Blinding of patients and treating physicians Triple blind trials: blinding of patients, treating physicians, and study investigators Details are on the 5th lecture
- 52. Types Of Clinical Trials Based On Study Designs Parallel design: each group of participants is exposed to only one of the study interventions Crossover design: each of the participants is given all of the study interventions in successive periods. Factorial design: when two or more experimental interventions are not only evaluated separately but also in combination and against a control. Traditional designs for clinical trials Details are on the 6th lecture
- 53. Special Design issues for small clinical trials A. Cluster randomized design B. Sequential design C. Adaptive design Details are on the 6th lecture
- 54. "superiority trials" (most) statistically significant "noninferiority trials” new treatment no worse than existing Rx "equivalence trials“ - x2 Rx indistiguishable Types Of Clinical Trials Based On hypothesis (superiority vs. noninferiority vs. equivalence) Details are on the 6th lecture
- 55. Other Types Of Clinical Trials By Outcome Of Interest (Efficacy Vs. Effectiveness) Test efficacy Highly selected participants Highly Controlled conditions Test effectiveness in every day practice Unselected Participants Flexible Conditions Give informed decisions about practice Explanatory RCTs Pragmatic RCTs Efficacy: Investigates the benefits of an intervention under ideal and highly controlled conditions Effectiveness: Examine the outcomes of interventions under circumstances that more closely approximate the real world
- 57. The major ethical principals in clinical trials Lecture Outline
- 58. Clinical trials should follow 3 principles: 1. Beneficence: which require that good should result, harm should be avoided, or that benefits should justify the expected risk or harm 2. Respect for rights: including the free choice of the subject and protection for those diminished autonomy 3. Justice: which require an equal distribution of burden and benefits Ethical Issues In Clinical Trials Details are on the 3rd lecture