Designing Your RCT: Research Question and Hypotheses

This is a crucial first step for any RCT! A well-defined research question and hypotheses will guide every other aspect of your study, from design and data collection to analysis and interpretation.

Let's break down how to craft these effectively.

1. Defining a Clear Research Question for an RCT

Your research question is the central inquiry your study aims to answer. For an RCT, it must be specific, answerable, and directly address the impact of your intervention.

Characteristics of a Good Research Question for an RCT:

• PICO(T) Format: This is the gold standard for clinical and intervention-based questions.


• Population: Who are you studying? (e.g., "Adults with Type 2 Diabetes," "Children aged 5-10 with ADHD")


• Intervention: What is the treatment/exposure you are testing? (e.g., "a new cognitive behavioral therapy program," "daily intake of Vitamin D supplements")


• Comparator: What are you comparing it to? (e.g., "standard care," "a placebo," "an existing treatment," "no intervention")


• Outcome: What are you measuring as a result? This should be your primary outcome. (e.g., "reduction in depressive symptoms," "improvement in glycemic control," "decrease in hospital readmission rates")


• (T) Timeframe (Optional but helpful): Over what period will the outcome be measured? (e.g., "after 12 weeks," "at 6-month follow-up")


• Feasible: Can you realistically conduct the study to answer this question?


• Ethical: Is it morally sound to conduct this study?


• Relevant: Does the answer to this question have practical or scientific importance?


• Specific and Unambiguous: Avoid vague terms. Everyone should understand what you're asking.

Template for an RCT Research Question:

"In [Population], does [Intervention] compared to [Comparator] lead to [Outcome] over [Timeframe**]?"

Examples:

• Medical Intervention:


• P: Adults aged 50-70 with newly diagnosed mild hypertension.


• I: Daily intake of a novel Angiotensin Receptor Blocker (ARB).


• C: Daily intake of a placebo.


• O: A significant reduction in systolic blood pressure (SBP) by at least 10 mmHg.


• T: After 12 weeks of treatment.


• Research Question: "In adults aged 50-70 with newly diagnosed mild hypertension, does daily intake of a novel ARB, compared to a placebo, lead to a significant reduction in systolic blood pressure (by at least 10 mmHg) after 12 weeks of treatment?"


• Behavioral/Educational Intervention:


• P: Children aged 8-10 identified with reading difficulties.


• I: A 10-week individualized literacy support program utilizing phonics-based digital modules.


• C: Standard classroom reading instruction.


• O: An improvement of at least one reading grade level as measured by the Woodcock-Johnson IV Tests of Achievement.


• T: At the end of the 10-week program.


• Research Question: "Among children aged 8-10 with reading difficulties, does a 10-week individualized literacy support program utilizing phonics-based digital modules, compared to standard classroom reading instruction, result in an improvement of at least one reading grade level at the end of the program?"


• Public Health/Policy Intervention:


• P: Households in low-income urban areas.


• I: A community-based healthy eating education program combined with subsidized access to fresh produce.


• C: A standard healthy eating education program without subsidized produce.


• O: A measurable increase in daily fruit and vegetable consumption.


• T: Over a 6-month period.


• Research Question: "In households in low-income urban areas, does a community-based healthy eating education program combined with subsidized access to fresh produce, compared to a standard healthy eating education program alone, lead to a measurable increase in daily fruit and vegetable consumption over a 6-month period?"

2. Defining Clear Hypotheses for an RCT

Hypotheses are testable statements derived from your research question. You'll typically have a Null Hypothesis (H0) and an Alternative Hypothesis (H1 or Ha).

A. The Null Hypothesis (H0)

• States there is no statistically significant difference or relationship between the intervention and the control group regarding the primary outcome.


• It's the hypothesis you are trying to disprove or reject with your data.


• Keywords: "no difference," "no effect," "no association."

B. The Alternative Hypothesis (H1 or Ha)

• States that there is a statistically significant difference or relationship between the intervention and the control group regarding the primary outcome.


• This is typically what you expect to find or what you're trying to demonstrate.


• Can be directional (e.g., intervention is better than control) or non-directional (e.g., intervention is different from control). Most RCTs use directional hypotheses (superiority or non-inferiority).

Types of Alternative Hypotheses in RCTs:

• Superiority Hypothesis (Most Common): The intervention is better than the comparator.


• H1: The intervention group will show a greater improvement (or less decline) in the outcome compared to the control group.


• Non-Inferiority Hypothesis: The intervention is not worse than an established comparator by more than a specified margin. Used when a new treatment might have other benefits (e.g., fewer side effects, lower cost) even if it's not superior in efficacy.


• H1: The intervention group is not inferior to the control group regarding the primary outcome, within a pre-defined margin (δ).


• Equivalence Hypothesis: The intervention is equally effective as the comparator, within a pre-defined margin.


• H1: The intervention group is equivalent to the control group regarding the primary outcome, within a pre-defined margin (±δ).

Characteristics of Good Hypotheses:

• Specific: Clearly defined population, intervention, comparator, and outcome.


• Testable: Measurable and observable.


• Falsifiable: It must be possible to disprove the null hypothesis.


• Aligned with Research Question: Directly addresses the RQ.


• Simple and Concise: Easy to understand.

Template for Hypotheses (Superiority):

• H0: There will be no statistically significant difference in [Outcome] between [Intervention] and [Comparator] groups in [Population] over [Timeframe].


• H1: [Intervention] will result in a statistically significant [improvement/reduction/increase] in [Outcome] compared to [Comparator] in [Population] over [Timeframe].

Examples of Hypotheses (corresponding to RQs above):

1. Medical Intervention (Superiority):

• Research Question: "In adults aged 50-70 with newly diagnosed mild hypertension, does daily intake of a novel ARB, compared to a placebo, lead to a significant reduction in systolic blood pressure (by at least 10 mmHg) after 12 weeks of treatment?"


• H0: There will be no statistically significant difference in the reduction of systolic blood pressure between adults aged 50-70 with mild hypertension receiving the novel ARB and those receiving a placebo after 12 weeks.


• H1 (Superiority): Adults aged 50-70 with mild hypertension receiving the novel ARB will demonstrate a statistically significant greater reduction in systolic blood pressure (by at least 10 mmHg) compared to those receiving a placebo after 12 weeks.

• Research Question: "Among children aged 8-10 with reading difficulties, does a 10-week individualized literacy support program utilizing phonics-based digital modules, compared to standard classroom reading instruction, result in an improvement of at least one reading grade level at the end of the program?"


• H0: There will be no statistically significant difference in reading grade level improvement between children receiving the individualized literacy support program and those receiving standard classroom reading instruction at the end of the 10-week program.


• H1 (Superiority): Children aged 8-10 with reading difficulties who receive the 10-week individualized literacy support program will demonstrate a statistically significant greater improvement in reading grade level (by at least one grade level) compared to those receiving standard classroom reading instruction.

• Research Question: "In households in low-income urban areas, does a community-based healthy eating education program combined with subsidized access to fresh produce, compared to a standard healthy eating education program alone, lead to a measurable increase in daily fruit and vegetable consumption over a 6-month period?"


• H0: There will be no statistically significant difference in the increase of daily fruit and vegetable consumption between households receiving the combined program and those receiving the standard program over a 6-month period.


• H1 (Superiority): Households in low-income urban areas receiving the community-based healthy eating education program combined with subsidized access to fresh produce will show a statistically significant greater increase in daily fruit and vegetable consumption compared to those receiving the standard program alone over a 6-month period.

Key Considerations When Defining Both:

• Primary vs. Secondary Outcomes: Your primary research question and hypotheses should focus on your primary outcome. You can have secondary research questions and hypotheses for secondary outcomes, but clearly differentiate them.


• Operational Definitions: Ensure all variables (intervention, comparator, and especially outcomes) are clearly defined and measurable. How will you measure "reduction in depressive symptoms" or "improvement in glycemic control"?


• Consultation: Discuss your question and hypotheses with experts in your field, statisticians, and methodologists. They can help refine them for rigor and feasibility.


• Pre-registration: Once finalized, it's highly recommended to pre-register your research question and hypotheses (e.g., on ClinicalTrials.gov or a similar registry) before data collection begins. This enhances transparency and reduces the risk of outcome switching or data-driven hypothesis generation.

To help me give you more tailored advice, please tell me a little bit about your potential RCT:

• What general area/field is it in? (e.g., medicine, psychology, education, public health)


• What is the intervention you are considering? (even a vague idea helps)


• What is the main problem you are trying to address?