Randomized controlled trials (RCTs) are considered the gold standard for evaluating the efficacy of therapeutic, preventive, and other measures. There are different types of RCT designs, including stratified, crossover, factorial, and cluster RCTs. Key steps in conducting an RCT include developing a protocol, selecting and randomizing a study population, implementing the intervention, following up participants, and assessing outcomes. RCTs aim to reduce biases by creating comparable intervention and control groups through randomization. While powerful, RCTs also have limitations such as cost, time requirements, and lack of applicability to entire populations. Reporting guidelines like CONSORT provide guidance on transparently reporting RCT methods and results.
An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups to receive and not receive an experimental preventive or therapetuic procedure, maneuver, or intervention .
An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups to receive and not receive an experimental preventive or therapetuic procedure, maneuver, or intervention .
Methods of randomisation in clinical trialsAmy Mehaboob
Randomization is the process by which allocation of subjects to treatment groups is done by chance, without the ability to predict who is in what group. A randomized clinical trial is a clinical trial in which participants are randomly assigned to separate groups that compare different treatments.
Randomized trials are gold standard of study designs because the potential for bias (selection into treatment groups) is avoided.
This document includes the purpose, types, advantages and disadvantages of each type of randomisation.
Methods of randomisation in clinical trialsAmy Mehaboob
Randomization is the process by which allocation of subjects to treatment groups is done by chance, without the ability to predict who is in what group. A randomized clinical trial is a clinical trial in which participants are randomly assigned to separate groups that compare different treatments.
Randomized trials are gold standard of study designs because the potential for bias (selection into treatment groups) is avoided.
This document includes the purpose, types, advantages and disadvantages of each type of randomisation.
Traditional RCT
Quasi-experiments
Cohort studies
Case Control Studies
Pragmatic trials
Non-inferiority trials
Complex interventions
The Trend statement
Randomized Control Trials
Enigma of Blinding Unraveled
Introduction
RCT
Steps in a RCT
Allocation Concealment
Bias in RCT
Phases in RCT
Types of RCT
Study Designs of RCT
Blinding
Methods of Blinding in different trials
Assessment of Blinding
Un-blinding
Current Scenario of Blinding
CONSORT
Conclusion
References
Clinical Research Regulation:
Various types of Clinical Study, Phases of Clinical Trial, Clinical Trial Protocol..
Drug discovery and development together are the complete process of identifying a new drug and bringing it to market.
Discovery may involve
Screening of chemical libraries
Identification of the active ingredient from a natural remedy.
Design resulting from an understanding of the target.
Development includes 0
Studies on microorganisms and animals.
Analytical method development and validation
Clinical trials and ultimately regulatory approval.
Drug Development/Approval Process..
Types of Clinical Study: Descriptive and Analytical..
Difference between Case Control and Cohort Study
Phases of Clinical Study
Phase 0: Phase 0 includes exploratory, first-in-human (FIH) trials that are carried out in accordance with FDA regulations.
The single subtherapeutic doses are administered to 10 to 15 volunteers in phase 0 trials, which are also known as human micro dose studies. These trials provide pharmacokinetic data or aid in the imaging of certain targets without causing pharmacological effects.
Phase 1: The initial evaluation of a medicine is done in phase I studies, which use fewer healthy human participants.
Phase 1 typically involves 20 to 80 healthy volunteers who have the illness or condition. Patients are often only utilized when a drug's mechanism of action indicates that healthy individuals will not tolerate it.
Nonetheless, researchers carry out Phase 1 studies in patients with that particular form of diabetes if a new medication is recommended for use in diabetic patients.
Phase 2: The purpose of phase II studies, which involve larger patient populations (a few hundreds), is to confirm the results of phase I safety evaluations and examine the drug's efficacy.
These tests are insufficient to determine whether the medicine will be effective in treating patients.
Phase 3: Researchers plan Phase 3 studies to prove whether a product deals an action benefit to a specific people or not.
Sometimes known as pivotal studies/ pilot, these studies comprise 300 to 3,000 volunteers.
Phase 3 studies deliver most of the safety data.
Phase 4: Phase 4 trials are conducted when the drug or device has been approved by FDA.
These trials are also recognized as post-marketing surveillance involving pharmacovigilance and continuing technical support after approval.
There are numerous observational strategies and assessment patterns used in Phase 4 trials to evaluate the efficacy, cost-effectiveness, and safety of an involvement in real-world settings.
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
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Types of rct concepts and application
1. TYPES OF RCT-CONCEPTS AND
APPLICATION
DR.SHIBASISH BANERJEE
MD(PGT) COMMUNITY MEDICINE
SESSION:2014-2017
BURDWAN MEDICAL COLLEGE AND
HOSPITAL
MODERATOR-DR.SIMA ROY
1
3. History
• Ambroise pare (1510-1590) –Unintentional
unplanned trial during treatment of wound
with burning oil one group and digestive made
of oil of rose, turpentine oil and egg yolk
another group.
• James Lind- A planned trial of scurvy at 1747
over 12 sailors
• 47 year later he repeated this on entire ship
and the Admiralty made lemon juice a
required part of the standard diet of British
seamen 3
4. The Quasi-Experimental Design
• Experimental design
• Random allocation not done due to ethical
problem and practical feasibility
• Two types Non randomized concurrent trial
Trial using historical control
4
5. Continued….
• Non-Randomized Concurrent trial-
The subjects keep entering the study and are
divided into the two groups, not by random
allocation by the investigator but by various
other circumstances
Example- patients of IHD may automatically
get divided (depending on their clinical
condition, ability to pay etc.) into a group who
would continue on medical management and
another who would go up for surgical
treatment 5
6. Continued….
• Before and After trial using Historical control:
The results of a new medical procedure can be
compared with the results that used to come
up before the procedure was available.
Example: the results of selective vagotomy
may be compared with the earlier results
when truncal (and not selective) vagotomy
was used.
6
7. The Disadvantages of Quasi -
Experimental Design
• Intervention and control group may not be
comparable
• “Selection” factors may be operating; e.g.
patients who are taken into surgical treatment
group for IHD may be in a much better state of
cardiovascular function as compared to
medical treatment group.
7
8. Continued….
• Improvement noticed in a ‘before and after
trial’ may simply be because other patient
management techniques may also have
improved recently; or else because the data
collected earlier was incomplete or erroneous.
8
9. So what to do?
• To know the efficacy of any preventive
,therapeutic or public health policy it is
necessary to maintain non-predictibility in
group allocation which is not possible in quasi
experimental design.
• That is why in modern epidemiology RCT is
preferred experimental design.
9
10. Definition of RCT
• A randomized controlled trial is an
epidemiological experiment designed to study
the effects of a particular intervention(
therapeutic, preventive or public health policy
)in which study population are randomly (i.e.
by chance)allocated to intervention and
control equivalent groups and the results are
assessed by comparing outcomes.(Bonita 2nd
edition)
10
11. Objective of RCT
• To eliminate the possibility of predictability .
• To eliminate bias
11
16. Bias in RCT
• Subject Variation
• Observer Bias
• Bias in evaluation
• Publication bias
16
17. Blinding
• overcome these errors and bias
• Single Blind Trial
• Double Blind Trial- Most preferred
• Triple Blind Trial
17
18. Different designs of RCT
• Stratified RCT
• Cross over design
• Factorial design
• Cluster RCT
• Non-inferiority or Equivalence RCT
• Superiority RCT
18
19. Stratified Randomization
• In stratified randomization, we first
stratify(stratum = layer) our study population
by each variable that we consider important,
and then randomize participants to treatment
groups within each stratum.
• Can be done with most important prognostic
indicator eg. Age,sex
19
21. Cross over Design
• Planned Crossover-
Each patient can serve
as his or her own
control, holding
constant the variation
between individuals in
many characteristics
that could potentially
affect a comparison of
the effectiveness of
two agents in same
disease
• Unplanned crossover-
Here some study
subjects of one group
may be allocated to
other group due to
deterioration of
condition or refusal of
taking one group of
treatment in same
disease
21
22. Advantage of Planned Crossover
• Each subject serves as his or her own control
• Less sample size
• Improves on the ethical considerations since
all subjects are exposed to both therapies,
thus nobody is denied of the potential
advantages of
a particular therapy
• Efficacy of different doses of same drug can be
compared
22
23. Drawback of Planned Crossover
• Carryover effect and wash out period
• order in which the therapies are given may
elicit psychological responses
• Not possible if the new therapy is surgical or if
the new therapy cures the disease.
• Blinding sometimes not possible e.g. one
therapy oral and another parenteral
23
25. Drawback of Unplanned crossover
• Pose a serious challenge in analyzing the data
• Current practice is to perform the primary
analysis by “ intention to treat” or analyse as
you randomize
• “ per protocol analysis” reduce the benefit of
randomization
• Too many crossover difficult to interpret
• No of crossover should be kept minimum
25
26. Unplanned crossover in a study of cardiac bypass surgery and
the use of intention to treat analysis. A, Original study design. B-
D, Unplanned crossovers. E, Use of intention to treat analysis 26
27. Factorial Design
• Two testing drug of independent mechanism
can be tested simultaneously
• Economical
• Time consuming
• Less sample size
• Efficacy of two drugs can be analysed
separately
• Termination of trial can be done separately
27
32. Cluster RCT
Cluster randomization trials are experiments in
which intact social units or clusters of
individuals rather than independent
individuals are randomly allocated to
intervention groups
32
33. Example of CRT
• Medical practices selected as the
randomization unit
• Communities selected as the randomization
unit
• Hospitals selected as the randomization unit
in trials
33
34. Reasons for Adopting Cluster
Randomization
• Intervention naturally applied at the cluster
level
• Administrative convenience
• To avoid treatment group contamination
• To obtain cooperation of investigators
• To enhance subject compliance
34
35. Challenges of CRTs
• Unit of Randomization vs. Unit of Analysis
• Critical design
• Large no of sample and multiple cluster
• Analysis depends on design
• Blinding not possible always
• More chance of Post randomization
recruitment bias( Zelen design)
• Selecting unit of inference
35
36. Name of Some CRTS
• Control of sexually transmitted diseases for
AIDS prevention in
Uganda: a randomized community trial
• Promotion of Breastfeeding
Intervention Trial (PROBIT)
A Randomized Trial in the Republic of Belarus
• Effect of a participatory intervention with
women’s groups on birth outcomes in Nepal:
cluster-randomized controlled trial
36
38. Equivalence Study
• Also called non-inferiority study
• Efficacy of new cheaper therapies are
compared with existing expensive treatment
• Specially HIV drug
38
40. Types of RCT
• Clinical Trial
• Field Trial
• Risk Factor Trial
• Health Services Evaluations Trials
• Cessation Experiment
• Trial of Etiological agent
40
41. Clinical Trial
• The “unit of study” in a clinical trial are
“patients” suffering with a given disease, the
therapy of which is to be studied.
• Examples are drug trials, trials of surgical
procedures or other medical therapeutic
procedures concerned with individual patient
care.
41
42. Field Trial
• The unit of study are healthy individuals,
usually in the community.
• The trial is usually undertaken in respect of a
preventive procedure as a vaccine, sera,
chemoprophylaxis, personal protective
measures, etc.
• For example, the trial of injectable polio
vaccine
42
43. Risk Factor Trial
• Same as preventive trial except intervention is
a “conceptual” procedure
• e.g. asking a group of subjects (randomly
selected, of course) to start “regular physical
exercise”, Here, regular physical exercise is the
“intervention” of interest which is not
physically administrated (like a vaccine or
drug) but is rather a “conceptual” procedure
43
44. Health Services Evaluations Trials
• Basically, the architecture is the same as that
of community intervention trials, with an
added element of health economic analysis
• e.g. “whether to provide 10 Doctors or 100
Multipurpose health workers within the same
budget” or “whether to provide free oral
rehydration salt packets or else to provide
health education to mothers” etc
44
45. Cessation Experiment
• A harmful factor is “removed” from the
intervention group
• contemporary of “risk factor trial”
• e.g. a group of smokers, free of IHD, may be
randomly divided into two groups, and one
group may be asked to give up smoking, while
the other group continues to smoke; the two
groups are then followed up for development
of IHD
45
46. Trial of Etiological agent
• To confirm an etiological hypothesis
• Example-Trial for Retrolental Fibroplasia in
preterm newborn
46
47. Sample Size of RCT
• The difference in response rates to be detected
• An estimate of the response rate in one of the
groups
• Level of statistical significance (α)
• The value of the power desired (1 − β)
• Whether the test should be one-sided or two-
sided
47
50. Noncompliance
• Overt or Covert
• Dropouts
• Drop-ins
• Reduce the observed differnce between two
group
• Can be checked by urine test of
metabolites,providing detailed list of OTC drug
• Piloting and include compliers only?????!!!!
50
54. Generalizability of Results
• Internal validity
• External validity (Generalizability)
• To generalize the results information of what
extent of study population are representative
of defined population is necessary
• Generalization can also be done to total
population if sample size is large enough and
trial is multicentric
• Characterize non-participants and identify the
differences from participants
54
55. Advantages of RCT
• Gold standard for evaluating the efficacy of
therapeutic, preventive and other measures in
both clinical medicine and public health
• Removes biases
• Create two comparable groups
• Ensures temporal relationship between
exposure and outcome
• Builds up “faith” in the findings of the study.
55
56. Disadvantages of RCT
• Study of “risk factors” or “prognostic factors”,
one can not “randomly” allocate human
beings into two groups
• Sometimes it may not be ethical to randomly
divide, thus exposing the ‘exposed’ group to a
potentially harmful treatment or procedure;
or to deprive the ‘non exposed’ group of a
potentially useful measures
56
57. Continued…
• Unfortunately, most randomized trials do not
provide the information the physician would
need to characterize an individual patient
sufficiently to predict what responses his/her
patient might have to the therapies available
• Participants in randomized trials are usually
not representative of the general population
every time
57
59. Some Example of RCT
• The Hypertension Detection and Follow-up
Program
• The Multiple Risk Factor Intervention Trial
• Trial of Arthroscopy to Placebo
• Breast cancer and tamoxifen
• UKPDS(United kingdom Prospective Diabetic
Study
59
60. .Design of the Hypertension Detection and Follow-up
Program (HDFP). DBP, diastolic blood pressure.
60
62. CONSORT
• The CONSORT statement (Consolidated
Standards of Reporting Trials) comprises a
checklist of essential items that should be
included in reports of RCTs and a diagram for
documenting the flow of participants through
a trial.
• It is aimed at primary reports of RCTs with
two group, parallel designs.
62
63. Continued…
• The objective of CONSORT is to provide
guidance to authors about how to improve
the reporting of their trials.
• Trial reports need be clear, complete, and
transparent
• focuses on items related to the internal and
external validity of trials.
63
64. Continued…
• Report should include information about
approval by an ethics committee, obtaining
informed consent from participants, and,
where relevant, existence of a data safety and
monitoring committee.
64
65. Flow diagram of the progress through the phases
of a parallel randomised trial of two groups (that is,
enrolment, intervention allocation, follow-up, and
data analysis)
65
68. Sources
• Epidemiology Leon Gordis 5th Edition
• Jekel’s Epidemiology 4th Edition
• MODERN Epidemiology Rothman 3Rd Edition
• Basic Epidemiology Bonita 2nd Edition
• Who Afmc Book
• JAMA THE JOURNAL OF THE AMERICAN
MEDICAL ASSOCIATION · JANUARY 2001
• www.consort-statement.org.
68
69. Continued…
• American Journal of Public Health > March
2004 > Design and Analysis of Group-
Randomized Trials
• Current Issues in the Design of Cluster
Randomization Trials by Allan Donner, PhD,
FRSC Department of Epidemiology and
Biostatistics
The University of Western Ontario
London, Canada
69
70. Continued…
Journal of Evaluation in Clinical Practice, 11 ,
5, 479–483 Cluster randomized controlled
trials
Suezann Puffer BSc,1 David J. Torgerson PhD2
and Judith Watson PhD3
1Research Assistant, 2Director, 3Research
Fellow, York Trials Unit, Department of Health
Sciences, University of York,
York, UK
70