Session 1 - Research Questions & Protocol PDF

Session 1: Wed 25th Created @August 10, 2024 9:48 AM Tags Research Questions & Protocol: Reading list: PSBS0002: Core Principles of Mental Health Research | University College London (talis.com) Class Prep:...

Session 1: Wed 25th Created @August 10, 2024 9:48 AM Tags Research Questions & Protocol: Reading list: PSBS0002: Core Principles of Mental Health Research | University College London (talis.com) Class Prep: NOTES: Research questions, hypotheses and objectives Clinical practice increasingly guided by literature and trials - research community responsible for addressing well thought out and clinically relevant questions. Research Question Well defined and specific question guide study design, population and data collection/analysis. Familiarity with a subject helps to produce questions from gaps in knowledge within a subject are or field of study. Haynes suggests it’s important to know “where the boundary between current knowledge and ignorance lies”. Important to identify which clinical uncertainties could or should be studied and also rationalise need for their investigation. Increase knowledge via: Systematic literature review Patient/Proxy interviews and focus groups Expert consultants Session 1: Wed 25th 1  Awareness of trends and tech advances Understand existing up-to-date research - some institutions encourage applicants to conduct systematic reviews of available evidence if a recent review does not already exist and preferably a pilot or feasibility study before applying for a grant for a full trial. Develop any questions (primary and secondary) at the early stages. Any additional questions should never compromise the primary question - primary research question forms the hypothesis and study objectives. A sensible research strategy centers on a single primary research question, which guides the study plan. In a grant proposal, this question should be clearly stated at the end of the introduction, specifying the population, intervention, and relevant contextual factors. This focus enhances clarity throughout the research process. A good research question should include: Specifies target population Interests scientific community and public Has clinical relevance Advances field knowledge Complies with ethical and national research standards Session 1: Wed 25th 2  FINER criteria: General aspects of a good research question PICO(T) format: Specific framework for developing research questions Population of interest Intervention being studied Comparison group Outcome of interest Time frame of the study Benefits: Helps construct study framework Aids protocol development Guides inclusion/exclusion criteria Identifies patient groups to include Assists in choosing appropriate outcome measurement tools Population definition affects study validity: Narrow definition (strict criteria): Increase internal validity - more likely to be accurate for specific group studied Reduces bias - less chance of confounding factors influencing results Limits external validity and generalisability - may not apply broadly to other populations or to the general clinic settings Broad definition (loose criteria): Increases external validity - results more likely to apply to wider population More representative of clinical practice May increase bias - more potential for confounding factors Reduces internal validity - less certainty that observed effects are due to the intervention alone Session 1: Wed 25th 3  Key considerations: Balance between internal validity and generalisability when defining study population. Balance the need for rigorous, internally valid results with the desire for findings to be widely applied in clinical practice. The ideal research question should be both clinically relevant and answerable. Ensures the study has the potential to contribute meaningful findings to the field. Research Hypothesis Research question and hypothesis - should be developed before starting the study, question drives the hypothesis, avoid working backwards from data to create a question. Importance of pre-study planning - prevents spurious findings from multiple statistical tests and ensures data collection is focused and purposeful. Developing a hypothesis: Based on research question Guides sampling strategy, intervention, comparison, and outcomes Can be single or composite outcome Null hypothesis - initially used for statistical testing, states no difference between groups, After a null hypothesis, an alternate hypothesis states the expected difference. Session 1: Wed 25th 4  At the end of the study, the null hypothesis is then tested statistically. If findings are not statistically significant, we can’t reject the null hypothesis, though if significant, we can reject the null and accept the alternate (there is a difference in mean functional outcome between the study groups). Hypothesis testing determines whether observed differences in outcomes are due to genuine effects of the treatments or just random chance. One-sided vs two-sided hypothesis: One-sided: Specifies the expected direction of difference Two-sided: States a difference exists between experimental and control group, but doesn’t specify direction Use two-sided unless there’s good reason for one-sided One-sided is used when there’s a clear expectation of the direction of effect, while the two-sided is used when the direction is uncertain or when researchers want to be open to effects in either direction. Clinical equipoise (state of collective uncertainty in the medical community that ethically justifies conducting randomised trials to determine better treatment) - ethical principle for clinical trials, requires genuine uncertainty in the expert community about which treatment is better. E.g. a clinical trial is ethical only if the expert community is uncertain about the relative therapeutic merits of the experimental and control groups being evaluated. There must be an honest and professional disagreement among expert clinicians about the preferred treatment. Key points: States hypothesis at the beginning to guide research objectives Good hypothesis development supports appropriate research design Research Objective Primary objective should align with the study hypothesis. Be precise and clinically relevant, measuring outcomes that matter in practical settings. Study objective: Define specific aims of the study Session 1: Wed 25th 5  Should be clearly stated in the research protocol introduction Example: “This study will compare functional outcomes of computer-assisted vs free-hand acetabular component placement in total hip arthroplasty patients.” Characteristics of good objectives: Active statements about answering the research question May specify outcome measures Guide protocol development and study design Inform sample size calculations and study power Clinical relevance: Focus on outcomes important to patients Should impact clinical decision-making Enable meaningful clinician-patient discussions Example from literature: Study: Warden SJ, Metcalf BR, Kiss ZS, et al. Low-intensity pulsed ultrasound for chronic patellar tendinopathy: a randomized, double-blind, placebo-controlled trial. Rheumatology 2008;47:467–71. Research question: How does low-intensity pulsed ultrasound (LIPUS) compare with a placebo device in managing the symptoms of skeletally mature patients with patellar tendinopathy? Research hypothesis: Pain levels are reduced in patients who receive daily active- LIPUS (treatment) for 12 weeks compared with individuals who receive inactive- LIPUS (placebo). Objective: To investigate the clinical efficacy of LIPUS in the management of patellar tendinopathy symptoms. Conclusion The research question is the most crucial aspect of a research project Poor objectives and hypothesis can lead to project failure Session 1: Wed 25th 6  Developing a good research question, hypothesis, and objectives can be challenging. Critical appraisal of the research question is vital for applying findings to clinical practice. Dedicating resources, time, and effort to developing these three elements (question, hypothesis, objectives) is essential. Well-developed research elements guide the project, influence result interpretation, and impact publication efforts. Researchers should use available tips and guidelines to help formulate these key research components effectively. (1. Brian Haynes R. Forming research questions. J Clin Epidemiol. 2006;59:881– 6. [PMC free article] [PubMed] [Google Scholar] [Ref list]) WHO’s Policy on writing research protocols Part 1: Project Summary: Length & Format: 300 words max, one page (12-point font, single-spaced), separate page Content: Summarize key protocol elements: Rationale Objectives Methods Study population Time frame Expected outcomes Standalone overview of the project, no references to main protocol Quick, comprehensive project snapshot General Information Session 1: Wed 25th 7  Protocol title, protocol identifying number (if any), and date. Name and address of the sponsor/funder. Name and title of the investigator(s) who is (are) responsible for conducting the research, and the address and telephone number(s) of the research site(s), including responsibilities of each. Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the research Rationale & Background Information Specifies the reasons for conducting the research in context of current knowledge. Equivalent to introduction in a research paper. To include: Statement of need/problem that is the basis of the project Cause of the problem Possible solutions Should answer question of why and what: Why is the research necessary? What is its relevance? Problem description should include: Magnitude, frequency, affected geographical areas, ethnic and gender considerations of the problem. Followed by a brief overview of most relevant published studies Function: Contextualizes the proposal and establishes its importance References (of literature cited in preceding sections) References can also be listed at the end of Part 1. Study goals and objectives Goals are broad statements outlining the proposal’s overall aims and provide context for the proposal. Specific objectives state the research question precisely. Session 1: Wed 25th 8  Objectives should be simple, specific, and stated in advance Primary Objectives should be stated first, followed by Secondary Study Design Critical for scientific integrity and data credibility. Ensures study quality and reliability. Should specify: Type of study Research population or sampling frame Participant criteria (inclusion, exclusion, withdrawal) Expected duration The same study can be described in several ways - a complete description of the study should be provided. Methodology Should detail: Interventions - need thorough descriptions (e.g. drugs, devices, vaccines, or social interventions) / could also be in social sciences e.g. providing training or information to groups Procedures - can be biomedical or social science-based Measurements Observations Laboratory Investigations Describe all standardized procedures and techniques, providing bibliographic references if not already given. Include all data collection instruments (e.g., questionnaires, focus group discussion guides, observation forms, case report forms). For randomised controlled trials, describe: Randomisation and Blinding method/process Stopping rules Session 1: Wed 25th 9  Code-breaking procedures Include a flow diagram of study design and procedures with assessment timings. Safety Considerations Protocol should detail safety measures and include: Procedure for recording, reporting and following up on adverse events. Consider potential adverse effects of all research activities, incl. questionnaires. Follow-up Clearly specify fl/u procedure and duration. Include post-study fl/u - especially for adverse events. Extend fl/u beyond data collection phase if necessary. Data Management and Statistical Analysis Describe and outline data handling, coding and verification procedures and processes Specify statistical methods for analysis, incl. reason for sample size, power of study, significance level, procedures for handling missing or spurious data For qualitative studies, detail analysis approach Provide sufficient information to understand data processing and interpretation methods Quality Assurance The protocol should describe the quality control and quality assurance system for the conduct of the study, including Good Clinical Practice (GCP), follow up by clinical monitors, Data and Safety Monitoring Board (DSMB), data management etc. Expected Outcome Should explain: How the study will advance knowledge How its results may impact healthcare practices, systems, and policies beyond academic publications Dissemination of Results and Publication Policy Session 1: Wed 25th 10  How results will be shared with scientific media, the community, participants, and relevant policymakers. Should clarify the publication policy, incl. lead authorship and acknowledgment criteria. Duration Should specify the time each phase of the project is likely to take, along with a detailed month by month timeline for each activity to be undertaken. Problems Anticipated Discuss difficulties that the investigators anticipate in successfully completing their projects within the time frame stipulated and the funding requested. Should also offer possible solutions to deal with these. Project Management Describe the role and responsibility of each member of the team. Ethics Describe potential ethical issues Explain ethical approval process Detail informed consent process for participants Informed Consent Forms Provide in English and local languages Translate after English versions are approved by the Ethics Review Committee Provide separate, tailored forms for each participant group - e.g. healthcare users, providers Create distinct forms for each new intervention Ensure all participants receive appropriate information for informed decision- making Part 2 Budget Should contain a detailed item-wise breakdown of the funds requested for, along with justification of them. Session 1: Wed 25th 11  Other Support for the Project Should provide information about the funding received or anticipated for this project from other funding organisations. Collaboration with other scientists or research institutions Links to other projects Curriculum Vitae of Investigators The CV of the Principal Investigator and each co-investigators should be provided. Should not be more than one page. Other research activities of the investigators The Principal Investigator should list all current research projects they’re involved in, the source of funding of those projects, the duration of those projects and the percentage of time spend on each. Financing and Insurance If not addressed in a separate agreement, and where relevant should be described. Protocol Writing in Clinical Research 1. Definition and Purpose: A research protocol is a detailed plan guiding clinical trials, outlining procedures, participant eligibility, study duration, and safety measures. 2. Key Aims: Identify the research question and its significance. Review existing literature. Formulate hypotheses and objectives. Address ethical considerations. Suggest methodologies for achieving objectives. 3. Benefits: The protocol aids in planning, guides the research process, and helps estimate time and budget. 4. Essential Components: Title: Should be concise and informative. Session 1: Wed 25th 12  Administrative Details: Include a contents page and contact information for the research team. Project Summary: A brief overview of the protocol's essentials. Introduction: Background information leading to the study's aims. Study Objectives: Clearly stated aims that are specific, measurable, achievable, relevant, and time-bound (SMART). Methods and Materials: Detailed description of study design, population, sample size, interventions, and data collection methods. 5. Data Management and Analysis: Outline statistical methods for analysing data, including software used. 6. Project Management: Provide a timeline for activities and ensure team members are properly trained. 7. Strengths and Limitations: Discuss what the study can achieve and potential limitations. 8. Ethical Considerations: Ensure compliance with ethical standards, detailing risks, benefits, informed consent processes, and confidentiality measures. This summary encapsulates the critical elements necessary for developing a comprehensive research protocol, emphasizing the importance of clarity in objectives and methodology to ensure successful study outcomes. Read: Research Questions, Hypotheses and Objectives Website: WHO’s Policy on Writing Research Protocols Watch: Hypothesis Educational Cartoon in the Jungle Read: Protocol Writing in Clinical Research Read: Decisional Support for Young People who Self-Harm: Protocol for a Feasibility Trial Read: From Theory to Practice: Improving the Impact of Health Services Research Notes on Prep: Research Protocol Template Session 1: Wed 25th 13  Post Class: Quiz Notes: Intro to Core Principles - Research Questions & Design FINER - Criteria for good research questions: Feasible, Interesting, Novel, Ethical, Relevant Origins of research Questions: Personal interest/experience, clinical observation and inspiration EVIDENCE Immersion in literature is key to refining a question Systematic literature review Incremental progress - fundamental to the origins and evolution of research questions. Providing a foundation for scientific advancement, allowing researchers to build upon existing knowledge, refine methods, and gradually push the boundaries of understanding in their respective fields. Replications - useful and especially with better methods/different groups THEORIES: should explain how different factors are connected and suggest ways to make interventions work. Helping researchers create clear questions and practical solutions to explore further. Stakeholder views: what do service users and carers this is important? Hypotheses A proposed explanation for a phenomenon that is clear and testable Core of scientific method Session 1: Wed 25th 14  Any empirical study testing associations between phenomena should have a hypothesis that has been stated before the study is conducted Could also test additional secondary hypotheses - but should specify a primary hypothesis that is the main point of the study; stats are based on the assumption you are doing just one test Qualitative or descriptive studies - may have no hypothesis but always a specific research question Example of a good hypothesis: “In this study, we will test whether people who report that they experienced physical abuse at least once during their childhoods score on average higher on a measure of suspiciousness than people who do not report experiencing abuse.” Main types of MH research questions covered in module: Aetiology & Mechanisms: understand how and why MH problems arise and develop (neuroscience, psychological & epidemiological approaches) Treatment: to develop and test means of preventing or alleviating MH problems (trials and other evaluations) Experiences: understand what it’s like to have a MH problem in a variety of context and what impact societal responses have - qualitative research, PPI Course philosophy: neuroscience, psychological and social all valid and need to be integrated Designing a Protocol How Research Studies are Designed Principles: Start from clearly defined question Write a protocol Methods have pros and cons Session 1: Wed 25th 15  Good designs are collaborative Design should fit stage evidence has reached - the study design should be appropriate for the current level of knowledge and evidence available on a particular topic Keep it simple Publish protocol Structure of Protocol Intro: Context, current evidence and rational Aims and Objectives: Incl. main research question and, where relevant - hypothesis Methods: Setting, Sample, Measures, Interventions (if relevant) & Procedures Analysis plan Dissemination plans: Outlines the strategy for sharing and communicating research findings to relevant audiences Timing, staffing requirements, ethics and research governance, costs What to include in each section Intro: Defining key terms Current evidence - how does this research relate Research gaps - identify gaps or limitations in current literature Explain how this research will address those gaps Purpose and Objectives Clearly state purpose of study List primary and secondary objectives or research question Brief overview of methodology - high-level summary of the study design and methods Context: Put into context within the field Session 1: Wed 25th 16  Only include relevant studies, theories and references Justification/Significance of research Why it’s important? How it will contribute to existing knowledge? Outline potential benefits to individuals, society, or the field Potential impact of results - how it may affect healthcare, health systems, or policies Should follow and logical flow, starting with the background and current knowledge, identifying gaps, stating the purpose and objectives, and concluding with the potential significance and impact of the study. It should be concise with enough information to justify the need for the research. Aims, Objectives & Hypotheses Aims: Purposes, incl. the main research question to be examined Objectives: Tasks to be accomplished Hypotheses: Testable hypotheses need to be specified unless study is qualitative or purely descriptive Hypotheses is a possible solution to a research question, to be tested in the study. Based on previous evidence & theoretical assumptions about phenomena being investigated. To be formulated to clearly say at the end of the study whether or not it’s supported - needs to be very specific. Qualitative and descriptive studies need clear questions if not a hypotheses. Example: A controlled trial of motivational interviewing in dual diagnosis of Schizophrenia & Substance misuse Aim: To investigate whether motivational interviewing is useful in reducing substance use among patients with “dual diagnosis” Objectives: 1) To describe how far patients with dual diagnosis attend and engage with a psychological intervention based on motivational interviewing. Session 1: Wed 25th 17  2) To compare post-intervention substance misuse levels between patients randomised to motivational interviewing or a placebo intervention consisting of supportive counselling. Primary Hypothesis: Post-Intervention substance misuse levels will be lower in the group receiving motivational interviewing intervention. Aim = what Objective = how (describe/compare) Hypothesis = testable statement Methods: Study design - clearly state type of study (e.g. randomised controlled trial, case-control etc.) & justify why this design was chosen. Study population and recruitment Group from drawn example Inclusion and exclusion criteria Recruitment method Sample size and justification/rational for this (e.g. power calculations) comparison groups within sample- how people are assigned Interventions - in treatment studies Details of interventions to be implemented (including control) How fidelity (adherence) to this is maintained and measured Setting - description/context where study is carried out Measures - What will be measured and how Reliability and validity of instruments Outcomes specified. Data collection All variables to be measured Session 1: Wed 25th 18  Data collection tools (e.g. questionnaires, lab tests) How measures are made and by whom Detail sequence of procedures Data management How data will be handled, coded and stored (data protection/governance) Quality control measures Statistical Analysis Methods to be used How missing or spurious data will be handled Ethical considerations Address safety concerns for participants Describe informed consent process Timeline Provide detailed schedule for each phase of the study Quality assurance Measures to ensure data quality and integrity Provide enough detail so another researcher could replicate the study based on the protocol. This section should be clear, concise, and logically organised, following the exact sequence of how the procedures will be executed. Analysis: Must be written in advance Quantitative which main descriptions or comparisons are to be presented, stating which are primary and secondary which statistical tests to be used for the analyses Qualitative Session 1: Wed 25th 19  Approach to be taken to data collection - e.g. thematic analysis aimed at identifying main themes, analysis based on grounded theory Tools to be used - e.g. software packages Additional elements State level of significance to be used Specify statistical test and justify choice Describe steps of performing test Handling of variables Describe how variables will be categorised or transformed - if applicable List the variables that will be used in the analysis Review possible confounding variables Subgroup analyses Specify any subgroup analyses Justify rationale Software/Statistical Package Mention software used and version & review Timeline - include timeline for when different analyses will be conducted Ensure analysis plan is appropriate and comprehensive for study design and research question. Dissemination: Identify target audience / show to disseminate to the people it matters to & method/channels Other researchers - e.g. via academic papers, conference presentations, relevant blogs, twitter Relevant clinicians, service planners, policy makers - e.g. seeking meetings, sending information to relevant individuals, professional publications, blogs, Twitter Service users, carers, the public - e.g. Open meetings, short summaries for participants, relevant charities, media and social media Session 1: Wed 25th 20  Objectives Goals for disseminating findings - e.g. raise awareness, influence policy, improve practice Timeline Provide schedule for when different dissemination activities ill occur throughout and after the project Responsibilities Assign roles and responsibilities for dissemination activities among them members Policy and Practice implications Indicate how results may impact healthcare, systems, or policies Describe plans for engaging policymakers or practitioners Evaluation Outline how you will assess the reach and impact of dissemination efforts Resources Specify budget, personnel, and other resources allocated for dissemination activities Ethical considerations Address any ethical issues related to disseminating findings Public and Patient Involvement (PPI): Increasing key in clinical research - hard to be funded without it. Stakeholders in research may be service users, carers, clinicians, service planners and policy makers, general public. Good to have involvement as early as possible. Involvement may include defining research questions, reviewing protocols and instruments, assessing ethics applications, interpreting and disseminating results. Service users may now be involved in all stages of research including collecting and analysing data (esp. qualitative) Session 1: Wed 25th 21  Lived experience, professionals, service users etc. - review question with those it can affect Help to make research more accessible - influence method and participation Other info in protocol: Time, staff and cost required Who’s involved in study - who are the investigators & doing what Explain impact/implications of research (e.g to NHS) - ?incorporate/change treatment - reality of implication in practice Timeline for steps of research, e.g. how long for recruitment/analysis, allow efficient time and account for why funding is needed for that duration (Gant chart or similar usually included). Practical Protocol review: Practical on protocols Induction day.docx (live.com) Strengths: Weaknesses: Review of previous research and giving Vague language and criteria/variables rational ?most appropriate age group Explaining importance and gap in ?reliability of response re: drug use - research particularly in that age group PPI work included Background: Aim: No explanation of key terminology there is an aim Too vague Methods: No reference to theories Setting is there Aim: Inclusion criteria No clear hypothesis No clear No quantifiable aim/hypothesis No objective Session 1: Wed 25th 22  Methods: Vague setting Unquantifiable exclusion criteria Vague recruitment process - needs more specification (e.g. “social networking sites”) Control group too vague - (e.g “young people”, “not take drugs”, ?duration of 5 years if researching onset of psychosis Sample: discussion of ethics and consent Analysis: No method of analysis - “closely examined” Doesn’t explain type of analysis No review of confounding variables Session 1: Wed 25th 23