Lecture 4: Scientific Research PDF

# Scientific Research **Assoc. Prof. Engy Ahmed Wahsh** Head of clinical pharmacy department Faculty of pharmacy, October 6 university ## Primary Clinical Study Designs - Observational - Descriptive - Case report or case series - Cross-sectional - Analytical - Cros...

# Scientific Research **Assoc. Prof. Engy Ahmed Wahsh** Head of clinical pharmacy department Faculty of pharmacy, October 6 university ## Primary Clinical Study Designs - Observational - Descriptive - Case report or case series - Cross-sectional - Analytical - Cross-sectional - Cohort - Case control - Interventional - RCT - Non-RCT ## Case Report and Case Series ### Definition The case report is a presentation of a case of a rare condition, unexplained condition, or a new symptom for a known disease, novel treatments, and unusual events. A case report describes one patient while case series report ≥2 cases combined into a descriptive review. ### Importance - Providing information about rare diseases - Describing a new symptom/association in an existing disease - Reporting of epidemiological outbreaks to national and international health authorities ### Advice for Writing a Case Report/Case series - Focus on what makes this case unique/interesting; The publication of the case report depends on how much the case is interesting and useful for the health community. - You must obtain patient consent to publish their case. - All patient information should be de-identified in the report. ### Notes - Note that the title does not state “study”. ### Example Possible adverse drug reactions in one or more patients: Example: QT-interval prolongation associated with fluoroquinolone antibiotics ### Advantages and Disadvantages | Advantage | Disadvantage | |---|---| | Easy to perform and inexpensive | Does not provide explanation other than assumption and does not establish causality or association | ### Follow the Standard Reporting Guidelines (CARE Statement) as Follows: - [1] Introduction - [2] Case presentation - De-identified demographic information - Clinical picture, symptoms, and main concerns - Medical, family, and social history - Clinical findings - Diagnostic assessment (difficulty of diagnostic assessment if present) - Therapeutic intervention (describe management in detail) - Follow up and outcomes (response, adverse events, re-intervention, unexpected events) - [3] Discussion - Strengths and limitations in your approach to this case. - Discussion of the relevant medical literature. - The rationale for your conclusions. - The primary "take-away" lessons from this case report. ## CARE Checklist of Information to Include When Writing a Case Report | Topic | Item | Checklist Item Description | Reported on Line | |---|---|---|---| | Title | 1 | The diagnosis or intervention of primary focus followed by the words "case report". | | | Key Words | 2 | 2 to 5 key words that identify diagnoses or interventions in this case report, including "case report". | | | Abstract (no references) | 3a | Introduction: What is unique about this case and what does it add to the scientific literature? | | | | 3b | Main symptoms and/or important clinical findings. | | | | 3c | The main diagnoses, therapeutic interventions, and outcomes | | | | 3d | Conclusion-What is the main "take-away" lesson(s) from this case? | | | Introduction | 4 | One or two paragraphs summarizing why this case is unique (may include references) | | | Patient Information | 5a | De-identified patient specific information. | | | | 5b | Primary concerns and symptoms of the patient. | | | | 5c | Medical, family, and psycho-social history including relevant genetic information | | | | 5d | Relevant past interventions with outcomes | | | Clinical Findings | 6 | Describe significant physical examination (PE) and important clinical findings. | | | Timeline | 7 | Historical and current information from this episode of care organized as a timeline. | | | Diagnostic Assessment | 8a | Diagnostic testing (such as PE, laboratory testing, imaging, surveys). | | | | 8b | Diagnostic challenges (such as access to testing, financial, or cultural) | | | | 8c | Diagnosis (including other diagnoses considered). | | | | 8d | Prognosis (such as staging in oncology) where applicable | | | Therapeutic Intervention | 9a | Types of therapeutic intervention (such as pharmacologic, surgical, preventive, self-care). | | | | 9b | Administration of therapeutic intervention (such as dosage, strength, duration) | | | | 9c | Changes in therapeutic intervention (with rationale). | | | Follow-Up and Outcomes | 10a | Clinician and patient-assessed outcomes (if available) | | | | 10b | Important follow-up diagnostic and other test results. | | | | 10c | Intervention adherence and tolerability (How was this assessed?). | | | | 10d | Adverse and unanticipated events. | | | Discussion | 11a | A scientific discussion of the strengths AND limitations associated with this case report. | | | | 11b | Discussion of the relevant medical literature with references. | | | | 11c | The scientific rationale for any conclusions (including assessment of possible causes). | | | | 11d | The primary "take-away" lessons of this case report (without references) in a one paragraph conclusion. | | | Patient Perspective | 12 | The patient should share their perspective in one to two paragraphs on the treatment(s) they received. | | | Informed Consent| 13| Did the patient give informed consent? Please provide if requested. | Yes/No | ## Observational Study Designs - Design Does Not Involve Investigator Intervention, Only Observation - It is essential to remember that observational study designs investigate associations - cannot prove causation. ### Types - Case-Control Study - Cohort Study - Cross-sectional ## Case-Control Study - Enroll subjects who have developed the outcome (cases) and subjects who have not developed the outcome (controls) and compare their risk factors, exposure histories, etc. - Study Exposure in Those with and without the Outcome of Interest - Determine the association between exposures/risk factors and disease/condition. - Classic example: Aspirin use and Reye syndrome - Retrospective studies - Practical method to study exposures in rare diseases or diseases that take long periods to develop - **Critical assumptions to minimize bias:** - Cases are selected to be representative of those who have the disease. - Randomly select cases when possible. - Controls are representative of the general population that does not have the disease and are as identical as possible to the cases, minus the presence of the disease so they are matched on factors of interest. - Information is collected from cases and controls in the same way. ### Advantages - Inexpensive and can be conducted quickly - Allows investigation of several possible exposures or associations, particularly when risk factors are unknown. - Allows study of rare diseases with a small sample size - No follow-up - Multiple risk factors explored ### Disadvantages - Confounding variables must be controlled. - Observational and recall bias: Looking back to recall exposures and their possible levels of exposure - Selection bias: Case selection and control matching are difficult. - Cannot calculate prevalence or incidence ### Measure of Association OR (odds ratio) ## Cohort Study - Determines the association between exposures/factors and disease/condition development. - Allows an estimation of the risk of outcome (and the RR between the exposure groups). - Study outcome of interest in those with and without the exposure of interest. - Describes the incidence or natural history of a disease/condition and measures it in time sequence - Retrospective (historical): Begins and ends in the present but involves a major backward look to collect information about events that occurred in the past ### Strengths: - Can calculate incidence - Structured collection of exposures and outcomes - Can infer temporal relationship ### Weaknesses: - Loss to follow-up - Non-random - Long duration - Large study needed to study rare outcomes - Expensive compared to other observational study ## Cross-Sectional Study - Identify the prevalence or characteristics of a condition in a group of individuals. ### Advantages - Easy design. - "Snapshot in time," all data collected at one time. - Studies are accomplished by questionnaire, interview, or other available biomedical information (e.g., laboratory values). - Short in duration (no follow-up period). - More feasible and inexpensive ### Disadvantages - Does not allow the study of a factor (or factors) in individual subjects over time, just at the time of assessment. - Difficult to study rare conditions. - Calculate prevalence, not incidence. - Timing between exposure and disease unclear ## Interventional Studies (Experimental Studies) ### Importance - To establish a causative relationship between exposure to a certain risk factor and outcome. - Also, to prove the safety and efficacy of interventions. ### Design - According to randomization: randomized vs. non-randomized studies - According to the control group: single-arm vs. controlled studies - According to phase: phase I, phase II, phase III, and phase IV - According to design: pragmatic vs. explanatory ## Types of Epidemiological Studies - **Analytical studies** - **Treatment (Experimental) studies** - **Randomized controlled trials** - **Randomized cross-over trials** - **Adaptive clinical trials** - **Non-randomized trials (quasi-experiment)** - **Observational studies** - **Cross-sectional studies** - **Cohort studies** - **Case-control studies** - **Ecological studies** ## The Standard Reporting Guidelines | Study Type | Checklist of reporting standards | Checklist Name | |---|---|---| | Randomized controlled pharmacotherapy trials | CONSORT - Consolidated Standards of Reporting Trials | CONSORT2010 checklist | | Observational epidemiology studies | STROBE - Strengthening the reporting of observational studies in epidemiology | STROBE Checklist | | Diagnostic Accuracy Studies | STARD - Standards for reporting diagnostic accuracy | STARD Checklist | | Systematic reviews Meta-analyses of controlled trials | PRISMA (formerly known as QUOROM) – Improving the quality of reports of meta-analyses of randomized controlled trials | PRISMA Checklist | | Meta-Analyses of Observational Studies | MOOSE - Meta-analysis of observational studies in epidemiology | MOOSE Statement | ## Think!!!!!!!!!! Public health officials want to assess the prevalence of smoking and its association with lung function among middle-aged adults in a specific city. They conduct a one-time survey with a representative sample of the population, collecting information about smoking habits and performing lung function tests. What type of study design is this? **Answer:** Cross-sectional study ## Random Allocation - In a randomized controlled trial (RCT), patients are randomized to the treatment groups. The random allocation is used to grantee the equal distribution of subjects to the treatment groups. While in the non-randomized controlled trial (also known as a quasi-experimental study), patients are allocated to treatment groups in a non-random manner as patient preference or physician judgment. ### Randomized Trials A comparative clinical trial where patients are allocated to the study groups in a random manner. ### Quasi-experimental Trials A comparative clinical trial where patients are NOT allocated to the study groups in a random manner but using a quasi-random method. ## Single-Arm vs. Controlled Trials - **Single-arm study:** A study includes one experimental group only. - **Controlled study:** A study that includes more than one group (experimental vs. control). ### Pragmatic Clinical Trials They aim to assess the safety and efficacy of an intervention in order to give a picture of the performance of this drug in clinical practice. Most of the clinical trials are pragmatic clinical trials. ### Explanatory Clinical Trials These trials are conducted for explanatory purpose with the aim to understand the mechanism of action of the intervention rather than estimating the efficacy of an intervention in the study population. ## Ethical Issues - All research studies must receive research ethics committee approval before being undertaken. - Considering that the investigators are 'intervening' in peoples' lives, RCTs raise a number of important ethical issues, including: - Clinical equipoise - Informed consent. ### Clinical Equipoise Healthcare professionals treating the patients must have sufficient doubt about the relative effectiveness of the treatments being compared. - There must be no evidence that the new intervention is better, worse or the same as any of the treatments currently being used in clinical practice, or the placebo. - If an effective treatment is available, the new intervention should be compared against this, not a placebo. - If these criteria are satisfied, the trial has 'clinical equipoise'. - There is clinical equipoise if there is an equal chance of benefit, harm or no effect, regardless of which treatment arm of the trial a study participant is randomized to. ## Challenges for Experimental Studies - Unethical (no equipoise) - Willingness to participate. - Too uncommon (observational studies more prevalent as they are easier and less expensive to conduct) ## Types Of Clinical Trials According To The Hypothesis And Comparing Groups - **Superiority Clinical Trials:** The authors aim to investigate whether the experimental drug is superior that the control drug. H1 X better than Y - **Non-inferiority Clinical Trials:** The authors aim to investigate whether the experimental drug is not inferior to the control drug. (the drug is not worse than the control group) H1 X NOT INFERIOR TO Y - **Equivalence Clinical Trials:** The authors aim to investigate whether the experimental drug and the control drug are equivalent to each others. H1 X EQUAL TO Y ## Efficacy In Atypical Clinical Trial Participants Versus Effectiveness In Real World | Item | Efficacy | Effectiveness | |---|---|---| | Definition | Highest (optimal) effect of the drug under standard conditions| Real-life effect of the drug in reality = in clinical practice = in real world = in real life | | Study Design | From clinical trials | From observational studies | | Population | Atypical subjects (patients) whom were selected accurately for the purpose of testing the efficacy of the drug | All the population in reality or in clinical practice |