randomised controlled trial
- 1. Dr Sridevi NH MBBS (MD) Community medicine Chikmagalur
- 2. Introduction Different study designs. The basic steps with an example Number needed to treat Types of RCTs Blinding and contamination Summary References
- 3. The randomized controlled trial (RCT) is one of the simplest, most powerful tools of research. The RCT is a study in which people are allocated ‘at random’ to receive one of several interventions. The intervention is controlled by the investigator
- 4. Interventions include varied actions such as preventive strategies, diagnostic tests, screening programs, and treatments.
- 7. Simple, two arm RCT. Cross over RCT design. Factorial RCT design.
- 10. HWilliams & Wilkins, 2001 ulley et al. Designing Clinical Research. 2ndEdition. Lippincott
- 11. Drawing up a protocol Selecting reference and experimental populations Randomization Manipulation or intervention Follow up Assessment of outcome
- 12. The protocol specifies the aims and objectives of the study. Criteria for the selection of study and control groups, sample size, procedure for allocation. The exposure variable, outcome variable, confounding variable and co interventions should be defined clearly. Inclusion and exclusion criteria should be enumerated. The protocol aims at preventing bias and to reduce the sources of error in the study.
- 13. Objective: To evaluate effect of stand-alone Care for Child Development, stand-alone Enhanced Nutrition, and Combined Care for Child Development and Enhanced Nutrition. All children aged birth to 2.5 months were enrolled and followed to age 2 years.
- 14. Reference/target population: population to which the findings of the trial, if found successful, are expected to be applicable. Experimental population: actual population that participates in the experimental study. ◦ Representative of the population ◦ Qualified or eligible for the trial. ◦ Informed consent.
- 15. Experimental population :children less than two years in Naushero Feroze district of Sindh Province, Pakistan. Reference population is children less than two years in other places of Pakistan
- 16. It is a statistical procedure. Assignment is predetermined Each individual has an equal chance of being allocated to all groups Best way to allocate participants to different intervention groups Ensures that the only difference between the two intervention groups is the intervention
- 17. Makes the Study and Control groups comparable Minimizes chance of confounding even against unknown confounders Selection Bias minimized Facilitates blinding / masking of treatment from participants and investigators
- 18. Unrestricted randomization: Simplest method – is tossing a coin, Use random number tables, Can use computers to generate random numbers. Restricted randomization Also called block randomization or balanced randomization
- 19. Randomization is done in blocks – each block will have equal number of subjects assigned to each group at the end of the block
- 20. Stratified randomization Block randomization may not protect against obtaining different distributions of important risk factors for the outcome in the study groups Used only when the results of the trial are thought to be related to a particular factor Ensures that different subgroups are balanced between treatment groups
- 21. Matched pair randomization: It can be used when the experiment has only two treatment conditions. Subjects are grouped into pairs based on some variable and then are randomly assigned to different intervention Cluster randomization: All the methods can be applied to either individuals or communities All individuals belonging to a specific group (village, ethnic, school etc.) communities are allocated intervention/placebo
- 22. The Trial was a cluster randomized controlled trial. 80 LHW catchment areas were selected for the study. Stand-alone Care for Child Development Stand-alone Enhanced Nutrition Combined Care for Child Development and Enhanced Nutrition Control group
- 23. Introduce the Intervention and Placebo Control Modalities. Deliberate application or withdrawal or reduction of the suspected causal factor as laid down in the protocol.
- 28. Examination of both the group subjects at defined intervals of time, under the same given circumstances, in the same time frame till final assessment of outcome. Follow up may be short or may require many years depending upon the study undertaken.
- 29. The study team undertook in-depth assessments when enrolled children were 6, 12, 18 and 24 months old.
- 30. The incidence of positive and negative results is rigorously compared in both the groups, if any differences are found: tested for statistical significance.
- 31. Child development: Measured at 12 and 24 months using the Bayley Scales of Infant and Toddler Development Four scales were used: ◦ the cognitive scale, ◦ the communication scale, ◦ the motor scale and ◦ the social-emotional scale
- 32. Child growth and nutrition status was measured by data collectors using multiple tools. Anthropometry (length/height, weight, mid-upper-arm circumference and head circumference) was taken at baseline (when each child was enrolled) and when children were 6, 12, 18 and 24 months old
- 35. Subject variation: participants may feel better or report improvement if they knew they were receiving a new form of treatment Observer bias: Investigator measuring the outcome of a trial may be influenced if he knows beforehand the particular procedure to which the subject has been subjected Bias in evaluation: Investigator may subconciously give a favourable report of the outcome of the trial.
- 36. Number of patients that need to be treated/ receive intervention in order to have an impact on one person For example, if 80% of patients in the control group got better and 90% of patients in a treatment group got better, the absolute risk of not getting better if denied the more effective treatment is 10%. NNT = 1/ (IE - INE) (where IE and INE are measured as proportions out of 1) For every 10 patients who get this treatment, 1 more would get better compared to the control group.
- 38. Number of patients that need to be treated/ receive intervention to in order to have one adverse outcome NNH = 1/ARI Absolute risk Increase Drug to decrease tumour size in colorectal cancer EER = 55/75=0.73 (Experimental Event Rate) CER=35/75=0.47 (Control Event Rate) ARI = 0.73 – 0.47 = 0.26 NNH= 1/ ARR = 1/ 0.26 = 4 Every four patients treated one will die
- 39. Clinical trials: aspirin on cardiovascular mortality Preventive trials:vaccines and chemo prophylactic drugs Risk factor trials :on CHD Cessation experiments: cigarette smoking and lung cancer Trial of etiological agents: oxygen for retrolental fibroplasia Evaluation of health services: domiciliary treatment for TB
- 40. Single Blind – Participant does not know which treatment received Double Blind – Doctor and Participant, both do not know which treatment received Triple Blind – Person analyzing the data, Doctor and Participant, all do not know which treatment received.
- 41. Study participants do not receive their allocated intervention / placebo Study participants receive the intervention even though they were in control group Tends to weaken the observed association
- 42. In summary, RCTs are quantitative comparative controlled experiments in which a group of investigators study two or more interventions in a series of individuals who are randomly ‘allocated’ to receive them.
- 43. Thank you
- 44. 1. Park K. Randomized contolled trials . Parks text book of Preventive and social medicine. 23rd edition. Jabalpur, M/S Banarsidas Bhanot Publishers. January 2015 page 80-87 2. Leon Gordis. Epidemiology 4th edition. Elsevier. 2009 page 131-163. 3. Roger detels. Oxford textbook of public health. 5th edition. Oxford 2009 page 527-556 4. Textbook of public health and community medicine 1st edition 2009. AFMC page 151-158 5. Hulley et al. Designing Clinical Research. 2ndEdition. Lippincott Williams & Wilkins, 2001
Editor's Notes
- #14: The PEDS Trial tested the effects on child development and growth of two intervention packages, Care for Child Development and Enhanced Nutrition, along with a third package that combined both interventions The Pakistan Early Development Scale-up (PEDS) Trial was implemented in Naushero Feroze district in Sindh Province, Pakistan from June 2009 through March 2012.