Evidence based medicine involves integrating clinical expertise with the best available external evidence from systematic research. Clinical trials generate safety and efficacy data on treatments and are conducted in multiple phases. Randomized controlled trials are considered the gold standard for clinical research as they minimize bias through randomization and use of control groups. Statistical considerations like sample size, endpoints, and interim analyses are important for clinical trial design.
In clinical trials and other scientific studies, an interim analysis is an analysis of data that is conducted before data collection has been completed. If a treatment is particularly beneficial or harmful compared to the concurrent placebo group while the study is on-going, the investigators are ethically obliged to assess that difference using the data at hand and to make a deliberate consideration of terminating the study earlier than planned.
In interim analysis, whenever a new drug shows adverse effect on human being while testing the effectiveness of several drugs, we immediately stop the trial by taking into account the fact that maximum number of patients receive most effective treatment at the earliest stage. Interim analysis is also used to possibly reduce the expected number of patients and to shorten the follow-up time needed to make a conclusion. One wouldn't have to spend extra money if he/she already have enough evidence about the outcome. In this presentation, the total sample size is divided into four equal parts to perform the analysis and decision is made based on each individual step.
Health outcomes research is seen as a cost-effective investment in measuring and defining value of new innovations in health care. We provide an overview of field and its applications
Introduction to meta-analysis (1612_MA_workshop)Ahmed Negida
Chapter 1: Introduction to Meta-analysis
- From the 1612 MA Workshop that will be held on 11th, December, 2016 at Dokki, Giza, Egypt
- Workshop instructor: Mr. Ahmed Negida, MBBCh candidate
Choice of control group in clinical trialsNagendra SR
To describe the general principles involved in choosing a control group for clinical trials intended to demonstrate the efficacy of a treatment and to discuss related trial design and conduct issues.
An Introductory Presentation to Clinical Research. A go through from this presentation will give you a brief and clear introduction about Clinical Research.
Steps in conducting a RCT
1. Drawing up a protocol
2. Selecting Reference & Experimental population
3. Randomization
4. Manipulation or Intervention
5. Follow up
6. Assessment of outcome
1. Drawing up a protocol
Aims and objectives of the study
Questions to be answered
Criteria for the selection of study and control groups
Size of the sample & allocation of subjects in both groups
Treatment to be applied - when, where, how
Standardization of working procedures and
Schedules as well as responsibilities of persons involved in the trial up to the stage of evaluation of outcome of the study.
2. Selecting Reference and Experimental Populations
Reference or target population - Population to which the findings of the trial, if found successful, are expected to be applicable (Eg: drugs, vaccines, etc.)
Experimental or Study population
Derived from the Reference population
Has same characteristics as the Reference population
Actual population that participates in the experimental study
Must give informed consent - Should be qualified or eligible for the trial
3. Randomization
Heart of the control trial
Procedure:
Participants are allocated into study and control groups
Eliminates bias and allows comparability
By random allocation every individual gets an equal chance for being allocated in to either groups.
4. Manipulation/ Intervention
Having formed the study and control group, the next step is to intervene or manipulate the study (experimental) group by deliberate application or withdrawal or reduction of a suspected causal factor
Eg: Drug, Vaccine, Dietary component, a habit
5. Follow up
Implies examination of the experimental and control group subjects at defined intervals of time in a standard manner, with equal intensity, under the same given circumstances in the same time frame till final assessment of outcome.
Attrition:
Inevitable losses to follow up (death, migration, loss of interest)
6. Assessment
a. Positive results:
Reduced incidence or severity of disease
Reduced cost to health service
Appropriate outcome in the study
b. Negative results:
Increased severity or frequency of side effects
Complications
Deaths
BIAS:
Any systematic error in the determination of association and outcome.
Bias may arise from errors of assessment of outcome due to human element
Subjective bias
Observer bias
Evaluation bias
1. Subjective Bias:
Participants, subjectively feel better or report improvement if they knew they were receiving a new form of treatment. This is known as “Subject variation”.
2. Observer Bias:
Investigator measuring the outcome of a therapeutic trial may be influenced if he knows beforehand the particular procedure or therapy to which the patient has been subjected.
3. Evaluation Bias:
Investigator may subconsciously give a favorable report of the outcome of the trial.
Blinding:
1. Single Blind Trial: Participant
2. Double Blind: Partcipant + Investigator
3. Triple Blind: Participant + Investigator + Data Analyzer
In clinical trials and other scientific studies, an interim analysis is an analysis of data that is conducted before data collection has been completed. If a treatment is particularly beneficial or harmful compared to the concurrent placebo group while the study is on-going, the investigators are ethically obliged to assess that difference using the data at hand and to make a deliberate consideration of terminating the study earlier than planned.
In interim analysis, whenever a new drug shows adverse effect on human being while testing the effectiveness of several drugs, we immediately stop the trial by taking into account the fact that maximum number of patients receive most effective treatment at the earliest stage. Interim analysis is also used to possibly reduce the expected number of patients and to shorten the follow-up time needed to make a conclusion. One wouldn't have to spend extra money if he/she already have enough evidence about the outcome. In this presentation, the total sample size is divided into four equal parts to perform the analysis and decision is made based on each individual step.
Health outcomes research is seen as a cost-effective investment in measuring and defining value of new innovations in health care. We provide an overview of field and its applications
Introduction to meta-analysis (1612_MA_workshop)Ahmed Negida
Chapter 1: Introduction to Meta-analysis
- From the 1612 MA Workshop that will be held on 11th, December, 2016 at Dokki, Giza, Egypt
- Workshop instructor: Mr. Ahmed Negida, MBBCh candidate
Choice of control group in clinical trialsNagendra SR
To describe the general principles involved in choosing a control group for clinical trials intended to demonstrate the efficacy of a treatment and to discuss related trial design and conduct issues.
An Introductory Presentation to Clinical Research. A go through from this presentation will give you a brief and clear introduction about Clinical Research.
Steps in conducting a RCT
1. Drawing up a protocol
2. Selecting Reference & Experimental population
3. Randomization
4. Manipulation or Intervention
5. Follow up
6. Assessment of outcome
1. Drawing up a protocol
Aims and objectives of the study
Questions to be answered
Criteria for the selection of study and control groups
Size of the sample & allocation of subjects in both groups
Treatment to be applied - when, where, how
Standardization of working procedures and
Schedules as well as responsibilities of persons involved in the trial up to the stage of evaluation of outcome of the study.
2. Selecting Reference and Experimental Populations
Reference or target population - Population to which the findings of the trial, if found successful, are expected to be applicable (Eg: drugs, vaccines, etc.)
Experimental or Study population
Derived from the Reference population
Has same characteristics as the Reference population
Actual population that participates in the experimental study
Must give informed consent - Should be qualified or eligible for the trial
3. Randomization
Heart of the control trial
Procedure:
Participants are allocated into study and control groups
Eliminates bias and allows comparability
By random allocation every individual gets an equal chance for being allocated in to either groups.
4. Manipulation/ Intervention
Having formed the study and control group, the next step is to intervene or manipulate the study (experimental) group by deliberate application or withdrawal or reduction of a suspected causal factor
Eg: Drug, Vaccine, Dietary component, a habit
5. Follow up
Implies examination of the experimental and control group subjects at defined intervals of time in a standard manner, with equal intensity, under the same given circumstances in the same time frame till final assessment of outcome.
Attrition:
Inevitable losses to follow up (death, migration, loss of interest)
6. Assessment
a. Positive results:
Reduced incidence or severity of disease
Reduced cost to health service
Appropriate outcome in the study
b. Negative results:
Increased severity or frequency of side effects
Complications
Deaths
BIAS:
Any systematic error in the determination of association and outcome.
Bias may arise from errors of assessment of outcome due to human element
Subjective bias
Observer bias
Evaluation bias
1. Subjective Bias:
Participants, subjectively feel better or report improvement if they knew they were receiving a new form of treatment. This is known as “Subject variation”.
2. Observer Bias:
Investigator measuring the outcome of a therapeutic trial may be influenced if he knows beforehand the particular procedure or therapy to which the patient has been subjected.
3. Evaluation Bias:
Investigator may subconsciously give a favorable report of the outcome of the trial.
Blinding:
1. Single Blind Trial: Participant
2. Double Blind: Partcipant + Investigator
3. Triple Blind: Participant + Investigator + Data Analyzer
Randomized control trial is so called because the patients who constitute the unit of study are allocated into ‘study group’ and ‘control group’ at random depending upon whether they receive or do not receive the intervention.
RANDOMIZED CONTROL trials
an assessment method
questions validity and applicability of many preventive and therapeutic procedures
reference Park's Preventive and social medicine
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. EVIDENCE BASED MEDICINE
• Definition:
“Evidence based medicine is the conscientious, explicit, and
judicious use of current best evidence in making decisions
about the care of individual patients.
The practice of evidence- based medicine means integrating
individual clinical expertise with the best available external
clinical evidence from systematic research”.
5. LEVELS OF EVIDENCE
• The levels of evidence outlined by Sackett and his colleagues in
2000:
• 1A = Systematic Review of Randomized Controlled Trials (RCTs)
• 1B = RCTs with Narrow Confidence Interval
• 1C = All or None Case Series
• 2A = Systematic Review Cohort Studies
• 2B = Cohort Study/Low Quality RCT
• 2C = Outcomes Research
• 3A = Systematic Review of Case-Controlled Studies
• 3B = Case-controlled Study
• 4 = Case Series, Case Reports
• 5 = Expert Opinion
6. SYSTEMATIC REVIEW
• Systematic review is usually restricted to review of RCTs
• A group of reviewers search the available literature via bibliographic
databases and retrieve copies of all the articles written on a specific topic
• Critical evaluation of the methodologies and content
• The final product is a synthesis of the properly completed and
meaningful research into information that is relevant to practicing
medical practitioners/clinicians
• Meta-analysis:
- A subset of systematic reviews that use statistical methods to combine
analyze multiple investigations
9. RANDOMIZED CONTROL TRIALS
• Study involves the randomization procedure
• Subjects in the study are randomly allocated to each group included
in the study
• Each subject has an equal chance of being assigned into an
intervention group, a control group, a placebo group
• Eliminates the over-representation of any one characteristic in one
group
• It eliminates any bias in the assignments of individuals
• Randomized controlled trials are known to be the ‘GoldStandard’
for establishing the effects of a treatment
11. CASE CONTROL STUDIES
• This design involves choosing 2 patients or 2 groups of
patients who were exposed to 2 different interventions
• The investigator retrospectively looks back to which group
or patient achieved a better outcome
12. COHORT STUDIES
• This design is also called a prospective study, or a longitudinal
study
• It involves the selection of a large population of people who
have the same condition and/or receive a specific intervention
• They are followed over time and compared to a group not
affected by the condition
• This study employs observation as the research methodology
• The interventions are not manipulated
13. CASE SERIES & CASE REPORTS
• Case series:
-Reports on a series of patients with a pre- identified
problem
• Case reports:
-This involves a report on the intervention and outcome
for a single patient
14. BOTTOM OF THE EVIDENCE PYRAMID
• Guyatt et al. label one type “physiological studies.”
• Oxford Center for Evidence-Based Medicine identifies these studies as
bench research and animal research.
• The other type is identified as unsystematic clinical observations,
unpublished evidence, or unpublished clinical observations.
• Conclusions drawn from bench (that is, basic) science and animal
research cannot be generalized directly to human patients.
15.
16. CLINICAL TRIALS
• Clinical trials are sets of tests in medical research and drug
development that generate safety and efficacy data
• Generate information about adverse drug reactions and
adverse effects of other treatments for health interventions
e.g.,
- drugs
- diagnostics
- device
- therapy protocols
17. WHY THEY ARE DONE?
1. As they provide better evidence of the effect or the outcome
that cannot be obtained with any other observational
method.
2. The variation is minimized and bias is controlled , hence
more valid and their results speak truth.
3. Providing maximum amount of assurance
4. Fastest and safest way to find treatments that work in
people and ways to improve health
18. WHEN THEY ARE DONE
• When the laboratory and animal studies yield the most promising
results of the intervention, those results are tested by clinical trials
• When the margin of the expected benefit or the outcome of an
intervention is doubtful or very narrow (10 to30% only).
• When the margin is large, obvious and beyond doubt, it will be
unnecessary to conduct clinical trials.
19. TYPES OF CLINICAL TRIAL
• Treatment trials
• Prevention trials
• Diagnostic trials
• Screening trials
• Quality of life trials
20. TREATMENT TRIALS
• New treatments
• New combination of drugs
• New approaches to Surgery
• New Radiation therapy
21. PREVENTION TRIALS
They try to find better ways to prevent disease in people and to prevent
disease recurrence using
Medicines
Vaccines
Vitamins
Minerals
Life style changes
22. DIAGNOSTIC TRIALS
To find better tests for diagnosis of a disease
To find better procedures for diagnosis of a disease
24. LIFE STYLE TRIALS
• Also called Supportive care trials
• Often employed for the chronically ill patients
• They explore the ways to improve comfort and
• to improve the quality of life
25. PURPOSE OF TRIALS
• Assess the safety and effectiveness of a
• new medication or device on a specific kind of patient
• different dose of a medication than is commonly used
• already marketed medication or device for a new indication
• Compare the effectiveness in patients with a specific disease of
two or more already approved or common interventions for that
disease
26.
27. RESEARCH QUESTION
• Start with a hypothesis
must be in the form of a statement
Null Hypothesis
Alternative hypothesis
• Then turn it into a specific question
the question must be “answerable”
this forms the basis of the study “Objectives”
28. PHASES OF TRIALS
• Phase 0:
• Phase 1:
• Phase 2:
• Phase 3:
• Phase 4:
Pharmacodynamics and
Pharmacokinetics
Screening for safety
Establishing the efficacy of the drug,
usually against a placebo
Final confirmation of safety and
efficacy
Sentry studies during sales
29. PHASES OF TRIALS
- 20-80
- Evaluate-
- Safety
- Determine a safe dose
- Identify side side effect
- First-in-human trials
-Single sub-therapeutic doses of
the study drug are given
-10 to 15
-preliminary data on the agent's
pharmacodynamics and
pharmacokinetics
Phase 0 Phase 1
30. PHASES OF TRIALS
- 100-300
- see if it is effective and to
further evaluate its safety
- 1,000-3,000)
- Effectiveness
- Collect information that will
allow it to be used safely
- Compare it to commonly
used treatments
- Postmarketing studies
- including the treatment's
risks
- Benefits
- Optimal use
Phase 4
Phase 3
Phase 2
31. MINIMIZING VARIATION
• The larger the variation, the more difficult it is to identify
treatment effects.
• Thus minimizing variation is a fundamental element of clinical
trial design.
• Inclusion Criteria
• Exclusion Criteria
32. RANDOMIZATION
• People are allocated at random to the treatment groups in the trial,
usually by using a computer program.
• This is done so that each group has a similar mix of people of
different ages, sex and state of health.
• If the people are allocated to the treatment groups at random, like
will be compared with like.
• If one group does better than the other, it is likely to be because of
the treatment, as the two groups are very similar in every other
way.
33. SIMPLE RANDOMIZATION
Think of tossing a coin each time a subject is eligible to be
randomized
HEADS: Treatment A
TAILS: Treatment B
Approximately ½ will be assigned to treatments A and B
Randomization usually done using a randomization schedule or
a computerized random number generator
May result in substantial imbalance in either
an important baseline factor and/or
the number of subjects assigned to each group
Solution: Use blocking and/or stratified randomization
34. BLOCKING
If we have two treatment groups (A and B) equal allocation, and a
block size of 4, random assignments would be chosen from the
blocks
1) AABB 4) BABA
2) ABAB 5) BAAB
3) ABBA 6) BABA
Blocking ensures balance after every 4th assignment
35. STRATIFICATION
• To ensure balance on an important baseline factor, create strata
and set up separate randomization schedules within each
stratum
• Example: if we want prevent an imbalance on age in a study,
first create the strata “< 75 years” and “ 75 years”
then randomize within each stratum separately
• Blocking should be also be used within each stratum
36. BLINDING
• Blinding is a fundamental tool in clinical trial design and a powerful
method for preventing and reducing bias
• Blinding refers to keeping study participants, investigators, or
assessors unaware of the assigned intervention so that this
knowledge will not affect their behavior, noting that a change in
behavior can be subtle, unnoticeable, and unintentional
• Single blind
• Double blind
• Triple blind
Single
blind
Double
blind
Triple blind
Outcome
assessor
X X X
Participant X X
Data
interpreter
X
37. SELECTION OF GROUP
Active Treatment Group
Group which is undergoing the research
Control group
provides data about what would have happened to participants if they
were not treated or had received a different intervention.
There are three primary types of control groups:
1) historical controls
2) placebo/sham controls
3) active controls
38. SELECTION OF GROUP
• Historical controls are obtained from studies that have already
been conducted and are often published in the medical literature
• placebo-controls he experimental intervention is compared with
intervention with a placebo
• active control is an active intervention that has often shown
effectiveness to treat the disease under study
39. PLACEBO CONTROL GROUP
• Participants are randomized to receive either the new intervention or a
placebo.
• Most placebo-controlled trials are also double blind
• Placebo-controlled trials also allow a distinction between adverse events
due to the intervention and those due to the underlying disease or other
potential interference
40. SELECTION OF A POPULATION
• In selecting a population to enroll into a trial, researchers must consider
the target use of the intervention since it will be desirable to generalize the
results of the trial to the target population.
• The selection of a population can depend on the trial phase since different
phases have different objectives.
• Early phase trials tend to select populations that are more homogenous
since it is easier to reduce response variation and thus isolate effects.
• Later phase trials tend to target more heterogeneous populations since it
is desirable to have the results of such trials to be generalizable to the
population in which the intervention will be utilized in practice.
41. SELECTION OF ENTRY CRITERIA
• consider the appropriateness of recruiting participants with various
conditions into the trial.
• Consider restricting entry criteria to reduce variation and potential
for bias.
• Entry criteria may need to be relaxed so that enrollment can be
completed within a reasonable time frame
42. SELECTION OF ENDPOINTS
• Selection of endpoints in a clinical trial is extremely important and
requires a marriage of clinical relevance with statistical reasoning
• Endpoints can generally be categorized by their scale of measurement.
• The three most common types of endpoints in clinical trials are
1. continuous endpoints (e.g., pain on a visual analogue scale)
2. categorical (including binary, e.g., response vs. no response) endpoints
3. event-time endpoints (e.g., time to death).
• Endpoints can be classified as being objective or subjective.
Objective endpoints- those that can be measured without prejudice
or favor..
Subjective endpoints - more susceptible to individual interpretation.
43. STATISTICAL CONSIDERATION
• At the planning stage some statistical considerations regarding the
manner in which the data will be tabulated and analyzed at the end
of the study should carefully be considered.
• It includes
1. Efficacy and safety assessment
2. Sample size estimation
3. Possible interim analysis and data monitoring
4. Clinical inference.
44. SAMPLE SIZE ESTIMATION
• For assessment of the effectiveness and safety of a study drug, a
typical approach is first to show that the study drug is statistically
significant compared to a placebo control.
• Statistically significant difference- high probability of correctly
detecting a clinically meaningful difference.
• The probability of correctly detecting a clinically meaningful
difference is known as the statistical power of the trial.
• In clinical trials, for a given significance level, we can increase the
statistical power by increasing the sample size.
45. INTERIM ANALYSIS AND DATA MONITORING
• A process of examining and/or analyzing data accumulating in a
clinical trial, either formally or informally, during the conduct of the
clinical trial.
• Provides an administrative tool for terminating a trial during which
either a superior efficacy or an excessive safety risk in the
treatment presented to patients is observed.
• If no interim analysis is intended, the reasons why an interim
analysis is not necessary for the study are to be clearly stated in the
study protocol.
46. STATISTICAL AND CLINICAL INFERENCE
• Statistical inference is only a part of induction process for the
conclusions obtained from clinical trials, and it should not preclude
the possibility of a meaningful clinical inference.
• Clinical inference is rarely based on the results of a single clinical
trial.
• In order to investigate the effectiveness and safety of a therapeutic
agent or a class of therapeutic agents, a series of clinical trials with
the same design and concurrent control is usually conducted over
patients with similar but different characteristics.
47. REFERENCES
• Umscheid CA, Margolis DJ, Grossman CE. Key concepts of clinical trials: a
narrative review. Postgraduate medicine. 2011 Sep 1;123(5):194-204.
• Evans SR. Fundamentals of clinical trial design. Journal of experimental
stroke & translational medicine. 2010 Jan 1;3(1):19.
• Chow SC, Liu JP. Design and analysis of clinical trials: concepts and
methodologies. John Wiley & Sons; 2008 Dec 4.
• Daly, Jeanne, et al. "A hierarchy of evidence for assessing qualitative health
research." Journal of clinical epidemiology60.1 (2007): 43-49.
• Evans CH, Ildstad ST. Small Clinical Trials. Issues and Challenges. 2001.