Chapter 4 · Starting a study
What goes into a research protocol?
Components of a proposal, with the project-proposal questions examiners set.
20 TNMGRMU questions answered hereset 21 times, 2013–2025
The problem first
You are a second-year MS resident. Your thesis protocol says you will "study the effect of music on anxiety before CABG". It lists three outcomes, gives no sample size calculation, and says the data "will be analysed using appropriate statistical tests".
Two years later the anxiety scores do not differ between the groups, but heart rate does. Your thesis reports heart rate as the main result. At the viva the examiner has your protocol open beside the thesis and asks one question.
"Which outcome did your protocol name as primary?"
Start here
Why write a protocol before you start?
A protocol is the written plan of a study, completed and approved before the first participant is enrolled. It fixes the question, the outcomes, the sample size and the analysis in advance, so that any later change is visible.
A protocol also lets others review the study before it begins. The ethics committee judges whether it is safe and fair. Scientific reviewers judge whether the design can answer the question. After the study, a reader can compare the report with the plan.
Research problem
How do you narrow a problem area into a problem you can study?
A topic such as surgical site infection is too broad to study. Narrow it step by step until the population, the setting, the comparison and the outcome are all named.
| Feature | Title | Statement of the problem |
|---|---|---|
| What it is | A one-line label for the study | A paragraph that explains why the study is needed |
| Contains | Population, intervention or exposure, outcome, setting, design | Size of the problem, what is already known, what is not known, and why it matters in your setting |
| Who uses it | Readers searching or scanning a list of studies | Reviewers deciding whether the study should be done |
| Common error | A vague topic: "A study of wound infection" | Repeating the title, or describing the disease without naming a gap |
Write the background impartially. Include published studies that disagree with your hypothesis, and explain why the question is still open despite them. A review that cites only supportive studies does not show that a new study is needed.
Components
What goes into a protocol?
The WHO format, ICMR 2017, ICH E6 and SPIRIT use different headings but ask for the same core parts. Each part answers one question that a reviewer will ask.
SPIRIT 2013 defines the protocol as a document detailed enough to understand "the background, rationale, objectives, study population, interventions, methods, statistical analyses, ethical considerations, dissemination plans, and administration of the trial". For a clinical trial, check your protocol against SPIRIT: 33 items in SPIRIT 2013, updated to 34 items in SPIRIT 2025 for randomised trials. For surveys, cohort and case-control studies, follow your institution's format or the WHO recommended format.
Consistency
How do the parts depend on each other?
The research question decides the objectives. Each objective needs an outcome variable, a basis in the sample size and a line in the analysis plan. Reviewers check that these match.
| Feature | Aim | Objectives |
|---|---|---|
| What it is | A broad statement of what the study hopes to achieve | Specific statements of the research question |
| How many | Usually one | One primary objective, plus secondary objectives if needed |
| Wording | General: "to reduce obesity in school children" | Measurable: "to compare the change in BMI-for-age z-score over one school year between intervention and control schools" |
| Used for | Setting the context | Choosing the outcome, the sample size and the analysis |
| WHO format | Goals are "broad statements of what the proposal hopes to accomplish" | Objectives should be "simple (not complex), specific (not vague), and stated in advance" |
Keep the objectives few, and write each one so that it can be measured. The research question chapter shows how to check an objective with the SMART checklist.
Confirmatory or exploratory?
ICH E9 (1998) defines a confirmatory trial as "an adequately controlled trial in which the hypotheses are stated in advance and evaluated", and says that "Each trial should address only a limited number of questions." It asks that "The protocol should make a clear distinction between the aspects of a trial which will be used for confirmatory proof and the aspects which will provide data for exploratory analysis." The same distinction helps in any thesis protocol.
| Feature | Confirmatory objective | Exploratory objective |
|---|---|---|
| Purpose | To test a hypothesis | To describe, estimate, or generate hypotheses for later studies |
| Hypothesis | Stated in the protocol before data collection | May be chosen after the data are seen (ICH E9: "the choice of hypothesis may be data dependent") |
| Sample size | Calculated for this outcome | Often not calculated for this outcome |
| How many | One, or very few | Several, if each is labelled as exploratory |
| In the thesis or paper | Reported as the main result | Reported as exploratory, to be confirmed by another study |
Chance of one or more false positives = 1 − 0.95k
For k = 10: 1 − 0.9510 = 40.1%
- k
- number of independent outcomes, each tested at the 5% level, when there is no real effect on any of them
- 0.95
- chance that one such test does not give a false-positive result
With 5 such outcomes the chance is 22.6%, and with 20 it is 64.2%. This is why a protocol names one primary outcome and labels the rest as secondary or exploratory. Methods that adjust for many comparisons are covered in the Practical Statistics chapter on multiple comparisons.
Interactive
Match each objective to its outcome variable, sample size basis and analysis
Try this: choose the analysis for objective 1, then find the objective that this survey cannot answer.
Teaching example: a hospital study of non-adherence among adults with type 2 diabetes, with a survey and in-depth interviews.
Before you start
Who reads your protocol before you enrol anyone?
Your guide, a scientific reviewer and the ethics committee. For a clinical trial, the trial must also be registered in the Clinical Trials Registry-India (CTRI) before the first participant is enrolled.
Approval covers the protocol as submitted. Under the Declaration of Helsinki (2024), "No amendment to the protocol may be made without consideration and approval by the committee", and a final report goes to the committee at the end of the study.
Before you submit, present the protocol at a departmental meeting. Ask the questions a critical reader would ask of the finished paper: could chance, bias or confounding explain the result you expect, and would a negative result be believed? Elwood (2002) called this use of critical appraisal at the design stage forward projection.
Feasibility
Can you finish the study in the time you have?
Work out how long recruitment will take from the number of eligible patients your unit sees, before you commit to a sample size and a submission date.
Months of recruitment = total sample size ÷ eligible patients per month
- Total sample size
- after adding for dropouts, for all groups together
- Eligible patients per month
- from last year's register, after applying the inclusion and exclusion criteria
92 ÷ 8 = 11.5 → 12 months. At 4 a month: 92 ÷ 4 = 23 months
Interactive
Change the recruitment numbers and watch whether the thesis is submitted on time
Try this: lower the consent rate to 70% and watch the thesis submission move past month 24.
Teaching example: the music therapy trial in this chapter, two groups. Patients enrolled a month = eligible patients a month × consent rate. Approvals take 4 months, CTRI registration 1 month, analysis 3 months and writing 4 months. Submission is due at month 24.
From the sample size calculation
More dropouts → more patients to recruit
From last year's register, after the eligibility criteria
Eligible patients who agree to take part
41 ÷ 0.9 = 45.6 → 46 per group, 92 in all · 8 × 100% = 8 enrolled a month · 92 ÷ 8 = 11.5 → 12 months
Recruitment fits. To submit by month 24, you need at least 7.7 patients enrolled a month (92 ÷ 12), and you expect 8.
Template
A general template for any proposal
Use these headings for a thesis protocol, a funding proposal or an exam answer. The last column gives one error to avoid under each heading.
| Heading | What to write | Error to avoid |
|---|---|---|
| Title | Population, exposure or intervention, outcome, setting, design | "A study of anxiety in cardiac patients" |
| Summary | Rationale, objectives, methods, population, time frame. WHO limit: 300 words | Written first and never updated |
| Background and rationale | Size of the problem, what is known, the gap, why now and here | A textbook chapter with no stated gap |
| Review of literature | Key studies, their results and their limitations | Only studies that agree with you |
| Research question and hypothesis | PICO or PECO. Null and alternative hypotheses for comparative studies | A hypothesis for a purely descriptive survey |
| Aim and objectives | One primary objective, secondary objectives, all measurable | No measure, only "to study", "to know", "to evaluate" |
| Study design and setting | Named design, place, study period | No design named, only "prospective study" |
| Participants | Inclusion and exclusion criteria, how they are identified | Exclusions that remove most real patients |
| Sampling | Sampling frame and method | Calling consecutive sampling "random" |
| Sample size | Formula, every assumed value and its source, adjustments | "30 per group, as in previous studies" |
| Intervention (trials) | Intervention and comparator in detail, randomisation, allocation concealment, blinding | No mention of who generates the allocation list |
| Variables and definitions | Each variable with an operational definition and unit | No haemoglobin cut-off for "anaemia" |
| Tools and data collection | Validated questionnaire or instrument, language, pretesting, who collects data, quality control | An unvalidated questionnaire written by the resident |
| Statistical analysis plan | Analysis for each objective, software, significance level, handling of missing data | "Appropriate statistical tests will be used" |
| Missing data and dropouts | How dropouts, protocol deviations, non-response and missing values will be recorded and handled in the analysis | Patients with missing outcomes left out without comment |
| Ethics | Committee, consent process and forms, confidentiality, risks and their management, compensation, CTRI | Nothing more than "ethics clearance will be obtained" |
| Timeline | Month-by-month chart | Recruitment that cannot fit the eligible patients |
| Budget | Item-wise costs with a justification for each | No cost for tests the patient would not otherwise need |
| Anticipated problems, limitations | Expected difficulties and what you will do about them | Left out |
| Contingency plans | What happens if recruitment is slow, a test kit runs out or a participant has a serious complication, and when the study would stop early | No plan for serious adverse events |
| Administration | Who does what: investigators, guide, statistician, and the laboratory, radiology or other departments whose work the study needs | Tests planned without the laboratory's agreement |
| Dissemination | Publication plan, feedback to participants and the community | Publication only if results are positive |
| References and annexures | Consistent reference style. Annexures: information sheet, consent forms, data collection form | Consent form only in English |
Related chapters: research question, sample size, choosing a test, research ethics, writing and referencing.
How dropouts and missing values can be handled in the analysis is covered in the Practical Statistics chapter on missing data.
Decide
Which design does the exam scenario need?
Scenario questions differ in what they ask you to do. Identify that first. The design follows from it, and the rest of the proposal follows from the design.
What does the scenario ask you to do?
Which design: all possible answers
- Cross-sectional survey with simple or systematic random sampling: Sample size from the expected prevalence and the precision you need. Report prevalence with a 95% confidence interval.
- Cross-sectional survey with cluster or multistage sampling: Multiply the sample size by the design effect, and take the clustering into account in the analysis.
- Analytical cross-sectional study: Measure the behaviour and the possible factors at the same time. Logistic regression gives adjusted odds ratios. It shows association, not cause.
- Qualitative study: In-depth interviews or focus groups with a purposive sample, continued until interviews stop adding new themes. Thematic analysis of transcripts.
- Mixed methods: A survey measures how common the behaviour is and which factors are linked to it. Interviews with a sample of those patients then explain why.
- Parallel-group randomised controlled trial: Random allocation with concealment, blinded outcome assessment where possible, sample size from the primary outcome, and CTRI registration before the first participant is enrolled.
- Cluster randomised trial: Randomise schools or villages, not individual children, so that the control group does not receive the intervention. Multiply the sample size by the design effect.
- Prospective cohort study: Measure the marker in people who do not yet have the outcome, then follow them up. Report incidence, relative risk or hazard ratio.
- Follow-up of confirmed cases, with a comparison group: Sample people with confirmed infection at least 3 months after onset, and a group without known infection. Use a published case definition.
Comparison
Protocol or thesis: what is the difference?
Both describe the same study. The protocol is written before data collection and states what will be done. The thesis is written afterwards and reports what was done and what was found.
| Feature | Protocol | Thesis or final report |
|---|---|---|
| Written | Before the first participant is enrolled | After data collection and analysis |
| Tense | Future: "will be randomised" | Past: "were randomised" |
| Results | None. Expected outcomes only | Results, discussion, conclusions |
| Reviewed by | Guide, scientific reviewers, ethics committee | Guide, university examiners, journal reviewers |
| Changes | Only through an amendment approved by the ethics committee | Departures from the protocol are reported and explained |
| Reporting guideline (trials) | SPIRIT | CONSORT |
The words "proposal" and "protocol" are often used for the same document. When a difference is intended, a proposal is written to obtain approval or funding and includes the budget and investigators' CVs. The protocol is the working plan the study team follows.
By specialty
Protocol problems by specialty
A thesis on medication adherence in type 2 diabetes measures adherence only by asking patients whether they take their tablets.
Write in the protocol how adherence will be measured (pill count, pharmacy refill records) and the cut-off that defines non-adherence.
Two wound-closure techniques are compared, and the operating surgeon chooses the technique for each patient.
The protocol must state how patients are allocated and who assesses the wound, and whether that person knows the allocation.
The protocol lists pain score, rescue analgesia, nausea and satisfaction, with no primary outcome.
Name one primary outcome and the time at which it is measured. Base the sample size on it.
A school survey plans to weigh children in front of their classmates.
Children are a vulnerable group (ICMR 2017). Plan parental consent, the child's assent, and private measurement.
A trial in pregnant women gives no plan for recording what happens to the baby.
ICMR 2017 lists pregnant or lactating women among women in special situations who may be vulnerable. Justify their inclusion and describe safety follow-up.
A study enrols inpatients with acute psychosis, some of whom cannot understand the consent form.
Describe how capacity is assessed and when a legally acceptable representative gives consent (ICMR 2017, 6.1.4).
An NCD survey measures blood pressure and blood glucose in 360 villagers, and the protocol ends at data collection.
State what happens to people found with raised blood pressure or glucose: feedback to them and referral for care.
Leftover serum from a serosurvey will be stored for future tests not yet decided.
The consent form must cover storage and future use of samples (ICMR 2017, Box 4.4 b, item 10).
Common myths
Common mistaken beliefs
Myth: The protocol is paperwork for the ethics committee.
It is the plan you will be held to. A change after approval needs the committee's approval first (Declaration of Helsinki, 2024).
Myth: I can choose the analysis after I see the data.
The analysis for each objective is written in advance. Choosing outcomes or tests after seeing results gives misleading findings.
Myth: An objective such as "to study obesity" is enough.
The WHO format says objectives should be simple, specific and stated in advance.
Myth: Questionnaire surveys do not need ethics review.
ICMR 2017 allows exemption only for less than minimal risk with no linked identifiers, and the ethics committee decides whether a proposal qualifies.
Myth: CTRI registration is only for drug trials.
CTRI expects registration of trials of any intervention, including surgical procedures, lifestyle changes and educational or behavioural treatment, and of clinical studies done as part of a PG thesis.
Myth: A protocol that covers every SPIRIT item is a good trial.
SPIRIT 2013 says the checklist should not be used to judge trial quality: a poorly designed trial can address every item by describing its poor design fully.
Why this matters to you
Five consequences of a weak protocol
Protocol sent back
A committee can return a protocol that has vague objectives, no sample size calculation or no analysis plan, and your start date moves.
A thesis that cannot answer its question
An objective with no matching variable or analysis is found only when you start writing the results.
Questions at the viva
Examiners compare the thesis with the approved protocol. Unexplained changes in outcomes or analysis are hard to defend.
A public record that differs from your paper
Trials registered in CTRI are searchable by anyone, and readers can compare the registered outcomes with the published ones.
Harm to participants
With no plan for adverse events, referral or confidentiality, participants carry risks the protocol did not manage.
History
History of the research protocol
- 1964
World Medical Association
Adopted the Declaration of Helsinki at its General Assembly in Helsinki.
- 1975
Declaration of Helsinki, Tokyo revision
Required that each experimental procedure "be clearly formulated in an experimental protocol which should be transmitted to a specially appointed independent committee for consideration, comment and guidance".
- 1996
ICH E6
The ICH Steering Committee approved the Good Clinical Practice guideline at Step 4 on 1 May 1996.
- 2004
An-Wen Chan and colleagues
Compared protocols with publications for 102 trials approved by ethics committees in Copenhagen and Frederiksberg. 62% had at least one primary outcome changed, introduced or omitted.
- 2009
Clinical Trials Registry-India
CTRI was launched on 20 July 2007 as a voluntary registry. From 15 June 2009 the Drugs Controller General (India) made registration mandatory.
- 2013
SPIRIT 2013
Published a 33-item checklist of the minimum content of a clinical trial protocol.
- 2017
ICMR
National Ethical Guidelines expanded four basic ethical principles into 12 general principles and listed what a protocol submitted to an ethics committee should include.
- 2025
ICH E6(R3) and SPIRIT 2025
ICH adopted E6(R3) on 6 January 2025. SPIRIT 2025, published in April 2025, revised the checklist to 34 items for randomised trials.
Guidelines
The research protocol in guidelines
"The design and performance of all medical research involving human participants must be clearly described and justified in a research protocol." It should include aims, methods, anticipated benefits and risks, qualifications of the researcher, funding, conflicts of interest, privacy provisions, incentives and compensation for harm.
"Clinical trials should be described in a clear, concise, scientifically sound and operationally feasible protocol." Appendix B lists the contents, from general information to statistics, ethics, data handling and publication policy.
The protocol submitted to the ethics committee should include, among other items, objectives, eligibility criteria, methodology with "sample size (with justification)", a "plan for statistical analysis of the study", consent forms "in English and local languages", and "plans for publication of results – positive or negative".
Minimum content of a trial protocol: 33 items in 2013, 34 items in 2025. The checklist covers content, not format, and does not prescribe how to design a trial.
All clinical trials conducted in India are to be registered "before the enrolment of the first participant". Clinical studies done as part of a PG thesis are also expected to be registered. Ethics approval, and DCGI approval where applicable, is required for registration.
A project summary of no more than 300 words, and a "detailed month by month timeline for each activity to be undertaken".
Steps
Turning an exam scenario into a proposal
- Underline what the question asks: measure how common, find reasons, test an intervention, or test a predictor.
- Write a specific title and a research question with population, exposure or intervention, comparison and outcome.
- Write one primary objective and two or three secondary objectives. State a hypothesis if the study compares groups.
- Name the design and justify it in one line.
- Define the population, eligibility criteria, sampling frame and sampling method.
- Calculate the sample size with stated assumptions, and label assumed values as assumptions.
- Define each variable, the tool that measures it and who collects the data.
- Write the analysis for each objective.
- Write the ethical issues specific to this group, not only "consent will be taken".
- Finish with timeline, budget heads, expected outcome and how results will be shared.
Reading a paper
Five checks against a study's protocol
- Does the paper give a registration number or cite a published protocol?
- Is the primary outcome in the paper the same as the one registered?
- Was the sample size calculation stated before the study, with its assumptions?
- Are subgroup and secondary analyses labelled as planned in advance or not?
- Are departures from the protocol reported and explained?
Why is it called that?
Word surgery
“Protocol”
Official rules of conduct, as in diplomatic or security protocol.
The written, approved plan of one study: question, methods, analysis and ethics.
“Objective”
Unbiased, not influenced by personal feelings.
A specific, measurable statement of what the study will find out.
For each objective, write down the variable that answers it and the analysis you will use. If you cannot, change the objective or the design.
Protocol
Greek prōtokollon: "first sheet glued onto a manuscript", from prōtos (first) and kolla (glue)
The sense moved from a first draft or official record to a set of rules. In research, the document that sets out the plan of a study.
Synopsis
Greek synopsis: "a general view", from syn- (together) and opsis (sight)
A short summary that gives a general view of the planned study.
Objective
The noun sense "goal, aim" dates from 1881, from the military term "objective point"
A point you set out to reach and can check whether you reached.
Feasible
Old French faisable: "that may be done", from faire (to do)
A feasible study can be completed with the patients, time, money and skills you have.
Vulnerable
Latin vulnerare: "to wound", from vulnus (wound)
Vulnerable participants are more likely to be harmed or wronged in research, and need added protection.
Exam answers
Model answer outlines
Essential components of a good research proposal (research protocol), and elements of a project proposal, with an example
Ph.D. RM 2013, 2014, 2016, 2018, 2019, 2020, 2021, 2022, 2023, 2025Definition: a research protocol is the written plan of a study, prepared and approved before the study starts. It states what will be done, how, and why (Declaration of Helsinki, SPIRIT 2013).
- Title page: title, investigators, guide, institution, version and date.
- Summary: rationale, objectives, methods, population, time frame (WHO: no more than 300 words).
- Introduction and rationale: size of the problem, what is known, the gap, why the study is needed.
- Statement of the problem: the gap in knowledge and why it matters in your setting. It is not the title repeated.
- Review of literature with references.
- Research question and hypothesis (PICO, null and alternative hypotheses).
- Aim and objectives: primary and secondary, specific and measurable.
- Methods: design. Setting and period. Population. Inclusion and exclusion criteria. Sampling frame and method. Sample size with formula and assumptions. Intervention, randomisation and blinding (trials). Variables with operational definitions. Tools and their validation. Data collection procedure. Quality control. Flow diagram.
- Data management and statistical analysis plan: analysis for each objective, software, level of significance, missing data, dropouts, non-compliance and non-response. Confirmatory and exploratory analyses kept separate.
- Ethical considerations: ethics committee approval, informed consent (information sheet and forms in English and local language), confidentiality, risks and their management, compensation, CTRI registration for trials.
- Timeline (Gantt chart) and budget with justification.
- Anticipated problems and limitations.
- Contingency plans: slow recruitment, shortage of kits or drugs, complications, rules for stopping early.
- Administration: roles of the investigators, guide, statistician and supporting departments.
- Expected outcome, dissemination and publication plan.
- References and annexures: consent forms, case record form or questionnaire, CVs.
Qualities of a good proposal: it answers a relevant question. Its objectives, variables, sample size and analysis match. It is feasible in time and cost, and ethical. It names one primary outcome and labels other analyses as secondary or exploratory. It is written in the future tense, clearly and concisely.
Example: use one scenario and fill each heading, for instance the dengue serosurvey outline below: title, objectives, cross-sectional design, multistage cluster sampling, sample size 854, IgG ELISA, seroprevalence with 95% CI, consent for blood and stored samples, timeline and budget.
Principles and techniques of writing the research proposal
Ph.D. RM 2025Principles
- Start from one clear research question. Write the objectives before the methods.
- State the problem, not a topic: name the population, the exposure or intervention, the outcome, the setting and the gap in knowledge.
- Review the literature impartially, including studies that disagree with your hypothesis.
- Separate confirmatory objectives (hypothesis stated in advance, few in number) from exploratory ones (ICH E9).
- Keep every part consistent: each objective has a variable, a basis in the sample size and an analysis.
- Be specific: operational definitions, named tools, numbers with their sources.
- Show feasibility: eligible patients per month, time, staff, cost.
- Build in ethics from the start, not as a final paragraph.
- Write in the future tense, plainly and concisely. ICH E6(R3) asks for a protocol that is clear, concise and operationally feasible.
- Follow the format of the institution, university or funding agency.
Techniques
- Make an outline under standard headings (see the template above).
- Search the literature and record the sources of every assumed value.
- Consult a statistician about design, sample size and analysis before the first draft is final.
- Pretest the questionnaire and, where useful, run a pilot study.
- Draw a flow diagram of participants and a Gantt chart of activities.
- Use a checklist: SPIRIT for trials, the institution's format for other designs.
- Have the guide and a colleague review it. Revise. Put a version number and date on each draft.
- Present the draft at a departmental meeting and appraise it as a reader of the finished paper would (forward projection, Elwood 2002).
- Submit for scientific and ethics review. Register trials in CTRI before enrolment.
Descriptive studies and causal studies, and factors affecting the research design
Ph.D. RM 2013, 2016, 2018, 2021| Feature | Descriptive studies | Causal (analytical, explanatory) studies |
|---|---|---|
| Question | How common, in whom, where, when? | Does this exposure or intervention cause this outcome? |
| Comparison group | Not required | Required |
| Hypothesis | Generates hypotheses | Tests hypotheses |
| Examples | Case report, case series, cross-sectional prevalence survey | Case-control, cohort, randomised controlled trial |
| Main output | Prevalence, incidence, distribution by person, place, time | Odds ratio, relative risk, hazard ratio, treatment effect |
| Main threat | Unrepresentative sample | Confounding and bias |
Factors affecting the choice of design:
- The research question and objective (describe, compare, test cause).
- What is already known: a new problem needs description first.
- Frequency of the outcome: rare outcomes favour case-control designs.
- Ethics: a harmful exposure cannot be assigned at random.
- Time available, and the interval between exposure and outcome.
- Budget, staff and laboratory facilities.
- Availability of a sampling frame and access to participants.
- Whether the variables can be measured reliably.
- The level of evidence needed by the people who will use the result.
See study designs for each design in detail.
General principles for research involving human subjects, format of a research proposal, and review procedures before starting
Ph.D. RM 20181. General principles (ICMR 2017): four basic principles (respect for persons, beneficence, non-maleficence, justice) expanded into 12 general principles:
- Essentiality
- Voluntariness
- Non-exploitation
- Social responsibility
- Privacy and confidentiality
- Risk minimisation
- Professional competence
- Maximisation of benefit
- Institutional arrangements
- Transparency and accountability
- Totality of responsibility
- Environmental protection
2. Format: the headings in the first answer above. ICMR 2017 Box 4.4 (b) lists what the ethics committee expects in the protocol.
3. Review procedures:
- Guide and department review.
- Scientific review of design, methodology, sample size and statistics.
- Institutional ethics committee: exempt, expedited or full committee review (ICMR 2017, Table 4.2). Research on vulnerable groups goes to full committee review.
- Regulatory approval where applicable (DCGI for drug trials that require it).
- CTRI registration of trials before the first participant is enrolled.
- During the study: amendments approved before they are implemented, adverse event reports, progress reports. At the end: a final report to the committee (Declaration of Helsinki, 2024).
Good clinical practice in the clinical research protocol
MD Community Medicine 2025GCP for clinical trials is set out in the ICH E6 guideline. The current version, E6(R3), was adopted on 6 January 2025. In India, also follow the ICMR 2017 guidelines and register trials in CTRI.
The 11 principles of ICH E6(R3), in brief:
- Ethical conduct in line with the Declaration of Helsinki. Participants&apos. Rights, safety and well-being come first.
- Freely given informed consent before participation.
- Independent review by an ethics committee. Conduct follows the approved protocol.
- Scientifically sound, based on current knowledge.
- Conducted by qualified individuals.
- Quality built into design and conduct. Critical-to-quality factors identified in advance.
- Processes proportionate to the risks and the importance of the data.
- A clear, concise, scientifically sound and operationally feasible protocol.
- Reliable results: fit-for-purpose data systems, record keeping, registration and results posting.
- Clear and documented roles and responsibilities.
- Investigational products manufactured to GMP and handled as per the protocol.
Protocol contents under GCP (ICH E6(R3), Appendix B): general information (title, identifying number, date, sponsor). Background. Objectives and purpose. Trial design (primary and secondary endpoints, type of design, randomisation and blinding, schedule of events, stopping rules). Selection of participants. Discontinuation and withdrawal. Treatment. Assessment of efficacy. Assessment of safety, including adverse event reporting. Statistics (sample size with its justification, level of significance, analysis population, missing data). Direct access to source records. Quality control and assurance. Ethics. Data handling and record keeping. Financing and insurance. Publication policy.
Ethical issues in research involving HIV-positive people, people with mental illness and other vulnerable groups
Ph.D. RM 2016, 2019- Who is vulnerable (ICMR 2017, Section 6): people relatively or absolutely incapable of protecting their own interests. Examples: children, pregnant or lactating women in special situations, people with mental illness or cognitive impairment, people with stigmatising or rare diseases, the economically and socially disadvantaged, prisoners, students and employees under a hierarchy.
- Inclusion: vulnerable groups have an equal right to be included so that benefits apply to them. Researchers must justify their inclusion. The Declaration of Helsinki (2024) allows research with them only if it responds to their health needs and cannot be done in a less vulnerable group, or if excluding them would worsen their disparities.
- Review: full ethics committee review, even when the risk is minimal.
- Consent: documented consent process. For those who cannot consent, a legally acceptable representative (ICMR 6.1.4), with the participant's assent where possible. Repeated information if needed. No coercion or undue influence.
- People with mental illness: assess capacity. Involve the representative when capacity is lacking. Record assent and re-consent when applicable (ICMR 6.2.4).
- HIV-positive people: strict privacy and confidentiality, since breach can increase vulnerability (6.1.5). ICMR allows confidentiality to be breached only in consultation with the ethics committee for valid scientific or legal reasons. HIV/AIDS is listed as a sensitive topic that may present special risks (6.2.8). Use codes instead of names, interview in private, and plan for stigma and discrimination.
- Support: counselling and referral systems for medical and social problems found during the study (6.2.11). Ancillary care where possible.
- Assurance: refusal or withdrawal does not affect the participant's treatment.
"A research problem well stated is research half done": explain
Ph.D. RM 2022The idea is from John Dewey, Logic: The Theory of Inquiry (1938): "It is a familiar and significant saying that a problem well put is half-solved."
- A clearly stated problem names the population, the exposure or intervention, the outcome and the setting. These decide the design, the sample and the variables.
- It shows the size of the problem and the gap in knowledge, which justifies the study to reviewers and funders.
- It leads directly to measurable objectives and, for comparative studies, a testable hypothesis.
- It limits the study to what can be answered, so the resident does not collect data that are never analysed.
- The title is not the statement of the problem. The statement explains the gap in knowledge and why it matters in the setting.
- A vague problem leads to vague objectives, an unjustified sample size and an analysis chosen after the data are seen.
Example: vague: "Anxiety in cardiac surgery patients." Well stated: "Among adults awaiting elective CABG at our hospital, does 30 minutes of recorded music before surgery lower the state-anxiety score compared with standard care?"
Project proposal: evaluating an intervention for obesity among adolescents or urban school children
Ph.D. RM 2017, 2023| Title | Effect of a school-based diet and physical activity programme on BMI among children aged 11–14 years in urban schools of [city]: a cluster randomised trial. |
|---|---|
| Background | WHO reports that overweight (including obesity) among children and adolescents aged 5–19 years rose from 8% in 1990 to 20% in 2022, and obesity from 2% to 8%. State the local data and the lack of evaluated school programmes. |
| Objectives | Primary: to compare the change in BMI-for-age z-score over one school year between intervention and control schools. Secondary: change in waist circumference. Proportion with obesity (BMI-for-age more than 2 SD above the WHO growth reference median). Physical activity and diet scores. |
| Hypothesis | H₀: no difference in mean change in BMI-for-age z-score between the groups. H₁: a difference exists. |
| Design | Cluster randomised controlled trial. Schools, not children, are randomised, because the programme is delivered to whole classes and children in the same school would share it. |
| Participants | Inclusion: children in classes 6–8 of participating schools. Exclusion: chronic illness or drugs affecting growth, inability to take part in physical activity. |
| Intervention and control | Intervention: daily supervised physical activity, nutrition classes, changes to school canteen food, sessions for parents. Control: usual curriculum, with the programme offered after the trial. |
| Randomisation | Schools stratified by government or private, allocated by a computer-generated list held by a person outside the study team. Measurers blinded to allocation. |
| Sample size (teaching example) | SD of change 0.5, difference to detect 0.15, α 5%, power 80%: 175 children per arm. Design effect with 50 children per school and ICC 0.02 = 1 + 49 × 0.02 = 1.98 → 347 per arm. With 15% loss: 409 per arm, or 9 schools per arm. |
| Tools | Calibrated digital scale, stadiometer, measuring tape. BMI-for-age z-score from the WHO growth reference for 5–19 years. Pretested activity and diet questionnaire. |
| Analysis | Intention to treat. Mixed-effects linear regression with school as a random effect, adjusted for baseline z-score. Proportions compared with methods that account for clustering. |
| Ethics | Children are a vulnerable group: parental consent and child assent. Permission from schools and the education department. Private measurement. No labelling of children. Referral of children with obesity. CTRI registration before enrolment. |
| Timeline and budget | Approvals 3 months. Baseline 1 month. Intervention one school year. Endline, analysis and report 3 months. Budget heads: staff, equipment, printing, travel, training. |
For adolescents outside school, use colleges or community wards as the clusters in the same way.
Project proposal: reasons for and factors influencing non-compliance in type 2 diabetes, with the statistical analysis plan
Ph.D. RM 2023| Title | Prevalence of and factors associated with non-adherence to diabetes medication among adults with type 2 diabetes attending [hospital]: a mixed-methods study. |
|---|---|
| Objectives | Primary: to estimate the proportion of patients who are non-adherent. Secondary: to identify factors associated with non-adherence. To explore patients' reasons in their own words. |
| Design | Phase 1: analytical cross-sectional survey. Phase 2: qualitative in-depth interviews with a purposive sample of non-adherent patients, continued until no new themes appear. |
| Participants | Inclusion: adults with type 2 diabetes on treatment for at least 6 months. Exclusion: cognitive impairment that prevents interview, acute illness. |
| Sampling | Systematic random sampling from the diabetes clinic register. |
| Sample size (teaching example) | Expected proportion unknown, so 50%. Precision ±5 percentage points, α 5%: n = 1.96² × 0.5 × 0.5 ÷ 0.05² = 384.2 → 385. With 10% non-response: 428. |
| Definitions | Non-adherence defined before data collection, for example taking less than 80% of prescribed doses by pill count (a cut-off chosen for this outline). Glycaemic control by HbA1c. |
| Variables and tools | Age, sex, education, income, cost of medicines, number of tablets a day, insulin use, side effects, knowledge, depression screen, distance to clinic. Pretested structured questionnaire in the local language. Pill count. Pharmacy refill records. Interview guide. |
| Statistical analysis plan |
|
| Ethics | Written consent. Confidentiality. Interviews by someone outside the treating team. Non-adherent patients referred to their physician for counselling. |
| Timeline | Approvals 3 months. Survey 6 months. Interviews 3 months. Analysis and report 3 months. |
Project proposal: reasons for and factors influencing non-compliance in HIV-positive patients, with the ethical issues
Ph.D. RM 2016| Title | Reasons for and factors associated with non-adherence to antiretroviral therapy among people living with HIV at the ART centre, [hospital]: a mixed-methods study. |
|---|---|
| Objectives | Primary: proportion non-adherent to ART. Secondary: associated factors. Reasons in patients' own words. Association of non-adherence with viral load. |
| Design | Analytical cross-sectional survey followed by in-depth interviews. |
| Participants and sampling | Adults on ART for at least 6 months, selected by systematic random sampling from the ART centre register. |
| Sample size (teaching example) | Expected non-adherence 30%, ±5 percentage points, α 5%: n = 1.96² × 0.3 × 0.7 ÷ 0.05² = 322.7 → 323. With 10% non-response: 359. |
| Measures | Pill count, pharmacy refill records, most recent viral load. Questionnaire on stigma, disclosure, side effects, alcohol use, travel cost, depression. |
| Analysis | Proportion with 95% CI. Chi-square. Multivariable logistic regression for adjusted odds ratios. Thematic analysis of interviews. |
| Ethical issues |
|
Project proposal: studying long COVID in your state
Ph.D. RM 2022| Title | Burden and pattern of post-COVID-19 condition among adults with laboratory-confirmed COVID-19 in [state]: a cross-sectional follow-up study. |
|---|---|
| Case definition | WHO Delphi consensus (Soriano and colleagues, 2022): symptoms in people with probable or confirmed SARS-CoV-2 infection, usually 3 months from onset, lasting at least 2 months, not explained by an alternative diagnosis. |
| Objectives | Primary: proportion of confirmed cases with post-COVID-19 condition. Secondary: symptom pattern. Effect on daily function and work. Factors associated (age, sex, severity of acute illness, vaccination, comorbidities). |
| Design | Cross-sectional follow-up of confirmed cases at least 3 months after onset, with a comparison group of people without known infection from the same areas, so that symptoms can be compared with their background frequency. |
| Sampling | Multistage: districts selected at random. Confirmed cases from state records, stratified by home isolation or hospital admission. Random selection within strata. Comparison group from the same areas. |
| Sample size (teaching example) | Expected proportion unknown, so 50%. Precision ±5 percentage points, α 5%: 385. Design effect 2 for multistage sampling: 770. With 20% non-response: 963. |
| Tools | Structured symptom questionnaire based on the case definition. A validated functional status or fatigue scale in the local language. Telephone or home interview by trained staff. |
| Analysis | Prevalence with 95% CI accounting for the survey design. Comparison with the uninfected group. Logistic regression for associated factors. |
| Ethics | Permission to use state records. Confidentiality. Recorded verbal consent for telephone interviews. Referral to a post-COVID or medicine clinic. |
| Timeline | Approvals and data access 3 months. Data collection 6 months. Analysis and report 3 months. |
Design a study of music therapy for anxiety in patients posted for CABG, and formulate the objectives
Ph.D. RM 2022| Title | Effect of music therapy on preoperative anxiety among adults scheduled for elective CABG: a randomised controlled trial. |
|---|---|
| Research question (PICO) | P: adults scheduled for elective CABG. I: 30 minutes of recorded music of the patient's choice the evening before and the morning of surgery. C: standard preoperative care. O: state-anxiety score before transfer to the operating theatre. |
| Hypothesis | H₀: no difference in mean state-anxiety score between the groups. H₁: a difference exists. |
| Objectives | Primary: to compare the mean state-anxiety score before transfer to theatre between the music and control groups. Secondary: to compare heart rate, blood pressure, the need for anxiolytic premedication and patient satisfaction. |
| Design | Parallel-group, two-arm randomised controlled trial, 1:1 allocation. |
| Participants | Inclusion: adults aged 18 years or more, elective CABG, able to hear and communicate. Exclusion: emergency surgery, hearing impairment, psychiatric illness on anxiolytics. |
| Randomisation and blinding | Computer-generated block randomisation. Allocation concealed in sequentially numbered opaque sealed envelopes. Outcome assessor blinded. Participants cannot be blinded to music. |
| Outcome measure | A validated state-anxiety scale in the local language, measured at baseline and before transfer to theatre. |
| Sample size (teaching example) | SD 8 points, difference to detect 5 points, α 5%, power 80%: n = 2 × (1.96 + 0.84)² × 8² ÷ 5² = 40.1 → 41 per group. With 10% dropout: 46 per group, 92 in all. |
| Analysis | Intention to treat. Independent t-test, or analysis of covariance adjusting for baseline score. Chi-square for categorical outcomes. |
| Ethics and registration | Written consent. Control group offered music after the outcome is measured. CTRI registration before enrolment. |
| Feasibility | At 8 eligible patients a month, recruitment takes 92 ÷ 8 = 11.5 → 12 months. |
Project proposal: seroprevalence of dengue in your city
Ph.D. RM 2019| Title | Seroprevalence of dengue virus infection among residents aged 5 years and above in [city]: a community-based cross-sectional serosurvey. |
|---|---|
| Background | The national serosurvey of 2017 (Murhekar and colleagues, 2019) found an overall dengue IgG seroprevalence of 48.7% in India, with wide regional variation. City-level data guide vector control and vaccine decisions. |
| Objectives | Primary: seroprevalence of dengue IgG antibodies. Secondary: age-specific seroprevalence. Association with household factors such as water storage and mosquito control. Proportion with a past diagnosis of dengue. |
| Design | Community-based cross-sectional serosurvey. |
| Sampling | Multistage cluster sampling: wards, then localities or census blocks within wards, then households at random. Eligible members of selected households. |
| Sample size (teaching example) | Expected seroprevalence 48.7% (national estimate), ±5 percentage points, α 5%: n = 1.96² × 0.487 × 0.513 ÷ 0.05² = 383.9 → 384. Design effect 2: 768. With 10% refusal: 854. |
| Laboratory | Venous blood. Serum separated and transported in cold chain. IgG by indirect ELISA in one laboratory with quality control. Kit and its validation stated. |
| Variables and tools | Age, sex, household water storage, mosquito control measures, past dengue diagnosis. Pretested questionnaire. |
| Analysis | Seroprevalence with 95% CI accounting for clustering. Age-specific estimates. Logistic regression for household factors. |
| Ethics | Consent for venepuncture. Parental consent and child assent for children. Consent for storage and future use of serum. Confidentiality. Results available to participants on request. |
| Timeline and budget | Approvals 3 months. Fieldwork 4 months. Testing 2 months. Analysis and report 3 months. Budget heads: ELISA kits, field staff, cold chain, transport. |
Frame a hypothesis and design a study of the association of "Protein-A" with the progression of diabetes mellitus to its complications
Ph.D. RM 2017| Hypothesis | H₀: baseline serum Protein-A level is not associated with the development of diabetic complications. H₁: adults with type 2 diabetes and high baseline Protein-A develop complications more often than those with low levels. |
|---|---|
| Design | Prospective cohort study. Protein-A is measured before any complication appears, so the time order of exposure and outcome is clear. A cross-sectional study could not show progression. |
| Participants | Adults with type 2 diabetes without the complications under study at baseline: normal urine albumin, no retinopathy on graded fundus photographs, no neuropathy on examination. |
| Exposure | Serum Protein-A by a validated assay at baseline. High and low groups by a cut-off stated in advance (for example, the median). |
| Outcomes | New nephropathy (persistent albuminuria), retinopathy, neuropathy over 3 years, each with a written definition. |
| Confounders | Age, duration of diabetes, HbA1c, blood pressure, lipids, smoking, treatment. |
| Sample size (teaching example) | Complications in 30% of the high group and 15% of the low group, α 5%, power 80%: 121 per group by the two-proportions formula. With 15% loss to follow-up: 143 per group, 286 in all. |
| Analysis | Incidence in each group. Relative risk with 95% CI. Kaplan–Meier curves. Cox regression for hazard ratios adjusted for confounders. |
| Ethics | Consent including storage of serum. Participants told of complications found and referred for treatment. Confidentiality. |
A quicker alternative is a nested case-control study using serum stored at the start of an existing cohort. See risk and survival.
Project proposal: identifying the problem of non-communicable disease in 10 villages covered by an NGO
Ph.D. RM 2015| Title | Burden of non-communicable disease risk factors among adults aged 18–69 years in 10 villages served by [NGO]: a cross-sectional survey using the WHO STEPS approach. |
|---|---|
| Objectives | Primary: prevalence of behavioural risk factors (tobacco use, alcohol use, physical inactivity, unhealthy diet) and biological risk factors (overweight and obesity, raised blood pressure, raised blood glucose, abnormal blood lipids). Secondary: proportion of people with raised blood pressure or glucose who were unaware of it. Access to care. |
| Design | Community-based cross-sectional survey. |
| Method (WHO STEPS) | Step 1: interview. Step 2: physical measurements (height, weight, waist, blood pressure). Step 3: biochemical measurements (blood glucose, lipids). The STEPS manual recommends a minimum age range of 18–69 years. |
| Sampling | All 10 villages included. Household lists from village records. Households selected by systematic random sampling in proportion to village size. One adult selected at random in each household. |
| Sample size (teaching example) | Expected prevalence of raised blood pressure 30%, ±5 percentage points, α 5%: 323. With 10% non-response: 359. Every village is included, so no cluster design effect is applied. |
| Analysis | Prevalence with 95% CI by village, sex and age group. Chi-square. Logistic regression for associated factors. |
| Ethics and action | Consent. Fasting instructions. Feedback of each person's measurements. Referral of people with raised blood pressure or glucose to the nearest health facility. Results shared with the NGO and the villages to plan screening and health education. |
| Timeline and budget | Approvals and training 2 months. Fieldwork 3 months. Analysis and report 2 months. Budget heads: field staff, blood pressure monitors, glucometers and strips, laboratory tests, transport. |
The one thing to remember
Write down the primary outcome, the sample size and the analysis for each objective before you enrol the first participant.
Sample sizes in the worked outlines use made-up values for teaching, except the dengue seroprevalence, which is the published national estimate. Formulas assume a two-sided α of 5%, Z values of 1.96 and 0.84, and rounding up.
Sources: World Medical Association. Declaration of Helsinki, 1964. Tokyo revision, 1975. Helsinki revision, October 2024. ICH E6(R3) Guideline for Good Clinical Practice, adopted 6 January 2025. Indian Council of Medical Research. National Ethical Guidelines for Biomedical and Health Research Involving Human Participants, 2017. World Health Organization. Recommended format for a research protocol (Research Ethics Review Committee). Chan AW et al. SPIRIT 2013 statement. Ann Intern Med 2013;158:200–7 (doi:10.7326/0003-4819-158-3-201302050-00583, PMID 23295957). Chan AW et al. SPIRIT 2025 statement. BMJ 2025;389:e081477 (doi:10.1136/bmj-2024-081477, PMID 40294953). Chan AW et al. Empirical evidence for selective reporting of outcomes in randomized trials. JAMA 2004;291:2457–65 (doi:10.1001/jama.291.20.2457, PMID 15161896). Clinical Trials Registry-India, ctri.nic.in. Soriano JB et al. A clinical case definition of post-COVID-19 condition by a Delphi consensus. Lancet Infect Dis 2022;22:e102–7 (doi:10.1016/S1473-3099(21)00703-9, PMID 34951953). Murhekar MV et al. Burden of dengue infection in India, 2017. Lancet Glob Health 2019;7:e1065–73 (doi:10.1016/S2214-109X(19)30250-5, PMID 31201130). World Health Organization. Obesity and overweight fact sheet. World Health Organization. WHO STEPS Surveillance Manual. Dewey J. Logic: The Theory of Inquiry. New York: Henry Holt, 1938. ICH E9 Statistical Principles for Clinical Trials, Step 4 version dated 5 February 1998. Elwood M. Forward projection: using critical appraisal in the design of studies. Int J Epidemiol 2002;31:1071–3 (doi:10.1093/ije/31.5.1071, PMID 12435787).
Past papers
Every TNMGRMU question on research protocol
Each one is answered in this chapter. Tap a sitting to open the university's own question paper.
- ×2As a researcher you are asked to evaluate an intervention to address the problem of obesity among adolescents. Write a detailed project proposal highlighting the research design and methods
- ×1Good clinical practice in clinical research protocol
- ×1Principles and Techniques of writing the Research Proposal
- ×1Describe the elements of a Project Proposal. Illustrate the preparation of Project Proposal with an example
- ×1a) Discuss the essential components of a research proposal. b) As a researcher you are asked to evaluate an intervention to address the problem of obesity among urban school children. Write a project proposal highlighting the research design and other components in research methods
- ×1As a researcher you are asked to identify the reasons for and factors influencing non-compliance among Diabetic (type 2). Write a detailed project proposal highlighting the research design including the plan for statistical analysis
- ×1a) Discuss the essential components of a research proposal. b) As a researcher you are asked to study the problem of long COVID 19 in your state. Write a project proposal highlighting the research design and other components in research methods
- ×1a) Design a research work to study to evaluate the effectiveness of ‘Music Therapy on relieving Anxiety among patients posted for CABG’. Also, formulate the objectives for the above problem statement. b) “A Research Problem well stated is Research half done” – Explain in detail
- ×1Explain the following research designs: Descriptive Studies and Causal Studies. Discuss in detail the essential components of a research proposal
- ×1What are the components of Good Research Proposal?
- ×1As a researcher interested in dengue, you are required to write a project proposal on seroprevalence of dengue in your city. Outline your project proposal highlighting the research design and methods
- ×1(a) Outline the key components of Research Protocol. (b) Discuss ethical issues on Research involving HIV +ve, mentally ill patients and other vulnerable groups
- ×1Explain the following research designs: (a) Descriptive Studies and Casual Studies. (b) Discuss in detail the essential components of a research proposal
- ×1Outline the general principles to be followed in designing any research involving human subjects. Indicate the format to be followed in writing up a research proposal and the review procedures to be undertaken before initiating the research proposal
- ×1Frame a hypothesis and design a research work to test association of “Protein-A” in the progression of a Diabetes Mellitus to its complications
- ×1You are interested in identifying the reasons for and factors influencing non-compliance in the patients diagnosed to be HIV +ve. Write a detailed project proposal highlighting the research design including the ethical consensus to be solved
- ×1Write in detail about the essential components of good research proposal and what are the factors affecting the research design?
- ×1As a researcher you are approached by an NGO to identify the problem of Non Communicable disease in the 10 villages covered by them. Frame a project proposal to address the same
- ×1Components of Research Proposal
- ×1(a) Explain the following research designs: Descriptive Studies and Causal Studies. (b) Discuss in detail the essential components of a research proposal