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Clinical trials its types and designs

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clinical trials- definition
types of clinical trials
various designs of clinical trials such as observational design and intervention design.

Published in: Health & Medicine
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  • DOWNLOAD THIS BOOKS INTO AVAILABLE FORMAT (2019 Update) ......................................................................................................................... ......................................................................................................................... Download Full PDF EBOOK here { https://soo.gd/irt2 } ......................................................................................................................... Download Full EPUB Ebook here { https://soo.gd/irt2 } ......................................................................................................................... Download Full doc Ebook here { https://soo.gd/irt2 } ......................................................................................................................... Download PDF EBOOK here { https://soo.gd/irt2 } ......................................................................................................................... Download EPUB Ebook here { https://soo.gd/irt2 } ......................................................................................................................... Download doc Ebook here { https://soo.gd/irt2 } ......................................................................................................................... ......................................................................................................................... ................................................................................................................................... eBook is an electronic version of a traditional print book THIS can be read by using a personal computer or by using an eBook reader. (An eBook reader can be a software application for use on a computer such as Microsoft's free Reader application, or a book-sized computer THIS is used solely as a reading device such as Nuvomedia's Rocket eBook.) Users can purchase an eBook on diskette or CD, but the most popular method of getting an eBook is to purchase a downloadable file of the eBook (or other reading material) from a Web site (such as Barnes and Noble) to be read from the user's computer or reading device. Generally, an eBook can be downloaded in five minutes or less ......................................................................................................................... .............. Browse by Genre Available eBooks .............................................................................................................................. Art, Biography, Business, Chick Lit, Children's, Christian, Classics, Comics, Contemporary, Cookbooks, Manga, Memoir, Music, Mystery, Non Fiction, Paranormal, Philosophy, Poetry, Psychology, Religion, Romance, Science, Science Fiction, Self Help, Suspense, Spirituality, Sports, Thriller, Travel, Young Adult, Crime, Ebooks, Fantasy, Fiction, Graphic Novels, Historical Fiction, History, Horror, Humor And Comedy, ......................................................................................................................... ......................................................................................................................... .....BEST SELLER FOR EBOOK RECOMMEND............................................................. ......................................................................................................................... Blowout: Corrupted Democracy, Rogue State Russia, and the Richest, Most Destructive Industry on Earth,-- The Ride of a Lifetime: Lessons Learned from 15 Years as CEO of the Walt Disney Company,-- Call Sign Chaos: Learning to Lead,-- StrengthsFinder 2.0,-- Stillness Is the Key,-- She Said: Breaking the Sexual Harassment Story THIS Helped Ignite a Movement,-- Atomic Habits: An Easy & Proven Way to Build Good Habits & Break Bad Ones,-- Everything Is Figureoutable,-- What It Takes: Lessons in the Pursuit of Excellence,-- Rich Dad Poor Dad: What the Rich Teach Their Kids About Money THIS the Poor and Middle Class Do Not!,-- The Total Money Makeover: Classic Edition: A Proven Plan for Financial Fitness,-- Shut Up and Listen!: Hard Business Truths THIS Will Help You Succeed, ......................................................................................................................... .........................................................................................................................
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Clinical trials its types and designs

  1. 1. Clinical Trials: Its types and designs From Devesh Aggarwal M.Pharmacy Department of Pharmacology ISF College of Pharmacy. Moga,Punjab
  2. 2. * 1. Introduction 2. Brief history 3. Types of clinical trials 4. Design of clinical trials a) Observational designs i. Cohort design ii. Cross sectional design iii. Case control study design b) Experimental designs i. RCT ii. NON RCT
  3. 3. * *Definition given by WHO *A clinical trial is any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. *Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc.
  4. 4. * *The concepts behind clinical trials are ancient. *The first proper clinical trial was conducted by the physician James Lind in 1747. *he included diet with acidic food at crew members of ship affected with scurvy. Crew divided in 6 groups including control group.
  5. 5. *Dates *In 1863, physician Austin Flint gave patients a fake remedy, for rheumatism later known as placebo effect. *1927 – The Bureau of Chemistry was renamed the Food, Drug, and Insecticide Administration (later known as the FDA ). This government division oversaw clinical research and eventually had to approve all drugs sold in the U.S. *1964 – After World War II, the research community saw a need for ethical codes. The Declaration of Helsinki created by the World Medical Association offered guidelines to physicians who used human subjects in their research.
  6. 6. *
  7. 7. Phase I Phase II Phase III Phase IV Objectives Determine the metabolic and pharmacological actions and the maximally tolerated dose Evaluate effectiveness, determine the short- term side effects and identify common risks for a specific population and disease Obtain additional information about the effectiveness on clinical outcomes and evaluate the overall risk-benefit ratio in a demographically diverse sample Monitor ongoing safety in large populations and identify additional uses of the agent that might be approved by the FDA Factors to be identified: • Bioavailability • Bioequivalence • Dose proportionality • Metabolism • Pharmacodynamics • Pharmacokinetics • Bioavailability • Drug-disease interactions • Drug-drug interactions • Efficacy at various doses • Pharmacodynamics' • Pharmacokinetics • Patient safety • Drug-disease interactions • Drug-drug interactions • Dosage intervals • Risk-benefit information • Efficacy and safety for subgroups • Epidemiological data • Efficacy and safety within large, diverse populations • Pharmacoecono mics Data focus: • Vital signs • Plasma and serum levels • Adverse events • Dose response and tolerance • Adverse events • Efficacy • Laboratory data • Efficacy • Adverse events • Efficacy • Pharmacoecono mics • Epidemiology • Adverse events
  8. 8. Phase I Phase II Phase III Phase IV Design features: • Single, ascending dose tiers • Unblinded • uncontrolled • Placebo controlled comparisons • active controlled comparisons • well-defined entry criteria • Randomized • Controlled • 2-3 treatment arms • broader eligibility criteria • Uncontrolled • observational Duration Up to 1 month Several months Several years Ongoing (following FDA approval) Population: Healthy volunteers or individuals with the target disease (such as cancer or HIV) Individuals with target disease Individuals with target disease Individuals with target disease, as well as new age groups, genders, etc. Sample size: 20 to 80 200 to 300 Hundreds to thousands Thousands Example: • Study of a single dose of drug X in normal subjects • Double-blind study evaluating safety and efficacy of drug X vs. Placebo in patients with hypertension • Study of drug X vs. Standard treatment in hypertension study • Study of economic benefit of newly- approved drug X vs. Standard treatment for hypertension
  9. 9. *
  10. 10. * Observational (non experimental) cohort Case control cross- sectional Experimental RCT Non RCT
  11. 11. * *A population at risk for the disease events is followed over time for the occurrence of disease and events. *This study used to estimate how often disease or life events happen in a certain population. *These are the best method for determining the incidence and natural history of a condition. Population (Sample) Exposed (smoking) Disease (Lung cancer) No disease Unexposed Disease (Lung cancer) No disease
  12. 12. * • A group of people is chosen who do not have the outcome of interest (for example, myocardial infarction). • The investigator then measures a variety of Variables that might be relevant to the Development of the condition. Prospective • These use data already collected for other purposes. The methodology is the same but the study is performed. • Outcome is already developed. Retrospective
  13. 13. * *Prospective *Studies carried out from present time to future *Can be tailored to collect specific exposure rate *But long wait for events to occur *Expensive *Prone to high dropout rates * Retrospective * Look at medical events from past to present * Information is available immediately * Difficulty in tracing subjects and doubt on quality of recorded information
  14. 14. * *Is a type of observational study that are primarily used to determine prevalence. *Prevalence equals the number of cases in a population at a given point in time. *All the measurements on each person are made at one point in time. Cohort Cross sectional Study group Population at risk Entire population Common measures Risks and rates Prevalence
  15. 15. * *The prevalence of a health outcome is simply the proportion of individuals with the health outcome in a population. Example *P1= a/a+b= 50/250 = 20.0% prevalence of CHD among people who are not active. *P0= c/c+d = 50/750 = 6.7% prevalence of CHD among people who are active. Prevalence Cases Total Population Present CHD Absent CHD Total Not active 50a 200b 250 Active 50c 700d 750 Total 100 900 1000
  16. 16. * *An observational study that compares patients who have a disease or outcome of interest (cases) with patients who do not have the disease or outcome (controls), and looks back retrospectively to compare how frequently the exposure to a risk factor is present in each group Study base Cases 50 exposed 40 unexposed 10 Controls 50 exposed 15 unexposed 35 Odds ratio (no of exposed cases)/(no of unexposed cases) (no of exposed control)/(no of unexposed controls)
  17. 17. * *Case control studies are usually retrospective. *In this study the only outcome is presence or absence of the disease or whatever criteria was chosen to select the cases. *Aim to identify predictors of an outcome *Permit assessment of the influence of predictors on outcome via calculation of an odds ratio *Can only look at one outcome *Bias is an major problem Odds Ratio : 40/10x35/15 = 4 x 2.33= 9.33odds of exposure for cases is 9.33 times that of controls Exposure is associated with 9x greater chance of disease.
  18. 18. • Efficient- saves time and energy • Used for rare diseases, small sample sizes • Can generate hypothesis for future study • Susceptible to bias-recall, reporting • Prone to methodological errors • Selection of an appropriate comparison group may be difficult * *
  19. 19. * *Interventional study (clinical trial) A type of clinical study in which participants are assigned to groups that receive one or more intervention/treatment (or no intervention) so that researchers can evaluate the effects of the interventions on health-related outcomes. Interventional study True experimental designs Quasi-experimental designs
  20. 20. * Also called nonrandomized interventional study design *In non randomly assigned control group studies, at least two separate groups are evaluated— *One of which receives the intervention of interest and another that serves as a control or comparison group. That means it is used to estimate the causal impact of an intervention on its target population without random assignment.
  21. 21. *When the act of random allocation may reduce the effectiveness of the intervention (occurs when the effectiveness of the intervention depends on the participant’s active participation which is influenced by their beliefs and preferences) *When it would be unethical to do random allocation *When it is impractical to do random allocation (e.g. Cost or convenience factors) *When there are legal or political obstacles to random allocation * When researchers can’t manipulate the independent variables * When researchers can’t randomly assign participants to groups. * Quasi independent variable is a naturally occurring variable and can’t be manipulated or eliminated. *
  22. 22. * • One group pre-test post-test design • Non equivalent control group design • Interrupted time series design
  23. 23. * * : Sample of violent adolescent women * : anger management class * : aggressive behaviour 1 year pre/post treatment If aggressive behaviour is lower at T2 than T1, can we conclude this decrease is caused by the treatment? Time 1 Intervention Time 2 01 X 02 Measures Treatment Example
  24. 24. * Target population selection Pre test Pre test Intervention X Activity as usual Post test Post test
  25. 25. * *Time series analysis is simply a set of measurements of a variable taken at various points in Time. *Essentially, the investigator measures the outcome of interest several times before initiating the experiment to establish a baseline value and trend in the data. After the intervention, the investigator will again measure the outcome several times to establish the impact of the intervention. : Mood of students during semester T1 T2 T3 T4 T5 T6 T7 T8 T9 A B C D X E F G H Example
  26. 26. * * An epidemiological experiment in which subjects in a population are randomly allocated into groups, usually called study and control groups, to receive or not receive an experimental preventive or therapeutic *Patients are randomly assigned to the study all groups that help in avoiding bias in patient Study population Intervention group Control group Outcome No outcome Outcome No outcome
  27. 27. * *Comparative *One treatment is directly compared to another to establish superiority. *Minimises bias *Randomisation minimises allocation bias and selection bias *Blinding minimises performance bias *Minimises confounding factors *Randomisation makes groups comparable according both known and unknown factors *Statistical reliability *Statistical test of significance is readily interpretable when the study is randomised
  28. 28. * *Might demand vast samples size, which require more resources from the investigators *Sometimes allocation of participants may be predictable and result in selection bias when the study groups are unmasked *Trials are of longer duration and more expensive *Results may not always mimic real life treatment situation (e.g. Inclusion / exclusion criteria; highly controlled setting) *Ethical limitations: some research cannot be ethically performed as an RCT (classically, RCT of the effects of parachutes on the survival of sky-divers)
  29. 29. *
  30. 30. Randomized Controlled Clinical Trial includes Diagnostic, Therapeutic, Prophylactic e.g. Evaluation of nitrates in reducing cardiovascular mortality Randomized Controlled Field Trial: It is similar to an Randomized Controlled Clinical Trial except that the intervention is preventive and not therapeutic. e.g. In this, the efficacy of a preventive intervention such as a new vaccine is tested in one study group and the other group receives a placebo or standard Preventive Trial: Trial of primary preventive measures e.g. Vaccines Risk Factor Trial: Investigator intervenes to interrupt the usual sequence in the development of disease for those individuals who have risk factor for developing the disease e.g. Primary prevention of CHD using simvastatin to lower serum cholesterol
  31. 31. * *According to level of blinding • In open RCT, everybody involved in the trial knows which intervention is given to each participant Open RCT • Patient or evaluator is blinded as to treatment, but not bothSingle blind • Neither patient nor outcome evaluator knows to which treatment patient was assigned Double blind • Patient, physician, and data analyst are blinded as to treatment identityTriple blind
  32. 32. * Parallel Cross-over Cluster Factorial
  33. 33. * *A parallel study is a type of clinical study where treatment and controls are allocated to different individuals. * In this two groups of treatments, a and b, are given so that one group receives only a while another group receives only b. Evaluation of outcomes Study population Treatment A Treatment B
  34. 34. * *This is unlike a crossover study where at first one group receives treatment A, followed by treatment B later, while the other group receives vice versa * Key element of this design is randomization *One treatment group, and one treatment-as-usual group. *Two active treatment groups. One of the groups might receive an active comparator (a treatment that’s known to be effective). ⁎ One treatment group, and one treatment-as-usual group. Two active treatment groups. One of the groups might receive an active comparator (a treatment that’s known to be effective). ⁎ However, these studies generally require large number of patients for the analysis *
  35. 35. * *In these types of studies each patient serves as his own control. Each patient gets both treatments. *Each patient receive first treatment then washout time is provided then other treatment is provided to the same. Study population Treatment A Treatment B Washout Period Treatment A Treatment B
  36. 36. * *Type of randomized controlled trial wherein groups of participants (as opposed to individual participants) are randomized and made into clusters. 10 hospitals Cluster randomisation (5xcluster of 2) Intervention 5 hospitals Control 5 hospitals Total study population, N=1000 Intervention, N=500 Control, N=500 Fig: flow chart representing cluster design
  37. 37. * *Studies involving two or more factors while randomizing are called factorial *Factorial design permits researchers to investigate the joint effect of two or more factors on a dependent variable. *Used when it is desired to study the influence of a number of factors on the treatments compared as well as their interaction with different treatments factors on a dependent variables l designs
  38. 38. * • An N of 1 trial is a clinical trial in which a single patient is the entire trial, a single case study. • In which one participant receives the experimental and the control interventions. 1. N-of-one trials • A massive clinical trial assessing the value of the therapeutic interventions by enrolling 10,000 or more subjects. 2. Mega trials
  39. 39. • It is a statistical analysis where the number of participants is not specified by the investigators beforehand. • Instead, the investigators continue recruiting participants until a clear benefit of one of the interventions is observed. 3. Sequential trials
  40. 40. * *Randomization is the random allocation of treatment, which means all participants have the same chance of being assigned to each of the study groups. The allocation, therefore, is not determined by the investigators, the clinicians, or other study participants The basic benefits of randomization include • Eliminates selection bias. • Balances arms with respect to prognostic variables (known and unknown). • Forms basis for statistical tests, a basis for an assumption-free statistical test of the equality of treatments
  41. 41. * *Any systematic deviation from true results. *It may be any error in the design, conduct or analysis of a study that results in distortion of truth. Experiment Untruth Untruth Truth
  42. 42. * Study design treatment Data collection Data analysis and publication Sources of Bias Investigator Participant Statistician Literature Instrument
  43. 43. * *Mann, C.J., 2003. Observational research methods. Research design II: cohort, cross sectional, and case-control studies. Emergency medicine journal, 20(1), pp.54-60. *Grimes, D.A. and Schulz, K.F., 2002. Bias and causal associations in observational research. The Lancet, 359(9302), pp.248-252. *www.who.int/topics/clinical_trials/en
  44. 44. THANKYOU FORPATIENCE

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