Here is the design of a clinical trial:

Official Title: STepped Exercise Program for Knee Osteoarthritis (STEP-KOA)

Included conditions:
- Osteoarthritis, Knee

Study Armgroups:
- {'label': 'STEP-KOA', 'type': 'EXPERIMENTAL', 'description': 'This is a stepped exercise program. It begins with an internet-based exercise training program (STEP 1). After three months, participants are assessed to see if they have achieved clinically meaningful improvement in key osteoarthritis outcomes. If so, they remain at STEP 1. If not, they move on to STEP 2, which adds telephone-based coaching. Participants are assessed again three months later. Those that still have not achieved clinically relevant improvement move on to STEP 3, which adds a series of in-person physical therapy visits.', 'interventionNames': ['Behavioral: Stepped Exercise Program']}
- {'label': 'Arthritis Education (AE)', 'type': 'ACTIVE_COMPARATOR', 'description': 'Participants in the AE control group will receive low literacy educational materials via mail every two weeks. Because STEP-KOA is a multi-component intervention, with participants receiving different numbers of Steps, it is not possible to implement a control condition that will mirror the exact intervention "dose" received by all participants in the STEP-KOA group. However, AE will achieve the goal of providing an active, OA-related control condition.', 'interventionNames': ['Behavioral: Arthritis Education']}

Interventions:
- {'type': 'BEHAVIORAL', 'name': 'Stepped Exercise Program', 'description': 'STEP 1: Participants have access to an internet-based exercise program for knee OA.\n\nSTEP 2: Participants have access to an internet-based exercise program for knee OA plus telephone support.\n\nSTEP 3: Participants have access to an internet-based exercise program for knee OA plus in-person physical therapy visit', 'armGroupLabels': ['STEP-KOA'], 'otherNames': ['STEP-KOA']}
- {'type': 'BEHAVIORAL', 'name': 'Arthritis Education', 'description': 'The arthritis education intervention will include bi-weekly mailings of low-literacy educational materials on a comprehensive set of topics related to OA and its management, based on established treatment guidelines.', 'armGroupLabels': ['Arthritis Education (AE)'], 'otherNames': ['AE']}

Primary Outcomes:
- {'measure': 'Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)', 'description': 'This is a measure of lower extremity pain (5 items), stiffness (2 items), and function (17 items), with items rated on a Likert scale of 0 (no symptoms) to 4 (extreme symptoms). The total scale range is 0-96, and higher scores mean a worse outcome.', 'timeFrame': 'Change from baseline to 3-month, 6-month, 9-month follow-ups. For STEP-KOA only, change from 9-month to 15-month follow-up.'}

Please estimate the sample size based on the assumption: 
80% power, alpha = 0.05, standard deviation = 17.5, correlation (rho) = 0.4, and approximately 20% attrition rate by 9 months.
Sample Size
          The sample size estimate of nÂ =â345 patients was based on a 2:1 randomization and the comparison of the primary outcome between the STEP-KOA and AE control arms at 9âmonths. Since AIM 3 is to describe the responder patterns for the Step progression in STEP-KOA we used a 2:1 randomization to facilitate our ability to evaluate these patterns [55]. For sample size calculations we used methods appropriate for Analysis of Covariance type analyses [56], which are equivalent in terms of efficiency to our linear model in randomized trials [49]. This method is based on performing a two-sample t-test sample size calculation for the between group difference and adjusting based on an assumed correlation between baseline and follow-up time point outcome measures. Based on our previous data, we assumed a correlation of 0.4 between baseline and follow-up WOMAC scores, a standard deviation of 17.5 and an attrition rate of 20% at 9-months [17, 57, 58]. With 80% power, alphaâ=â0.05, standard deviationâ=â17.5, rhoâ=â.4, and approximately 20% attrition rate by 9-months, 230 and 115 participants are needed in the STEP-KOA and AE groups, respectively, for an effect size of 0.33. This corresponds to a 5.8 point difference in mean total WOMAC scores at 9-months between STEP-KOA and AE, which is a clinically relevant improvement [59]. We are also powered to detect medium effect size differences in secondary study outcomes.
          
            Economic Evaluation
            The overall goal of Specific Aim #4 is to provide the VA with information about the value of the STEP-KOA program, from a cost effectiveness perspective. In addition to informing the VA regarding the overall average cost of STEP-KOA per patient, this evaluation will provide information on how much improvement in outcomes can be achieved for that cost. The analysis will begin with descriptive statistics of the cost and effectiveness (utility) data. We will examine each measure of effectiveness, WOMAC and mean QALY (and the pain/discomfort sub-core of the EQ-5D-5âL), using the general analytic procedures described above for primary and secondary outcomes. We will calculate the incremental cost effectiveness ratio (ICER) of STEP-KOA compared to the AE control group, separately for WOMAC and QALYs. The ICER will be calculated as the difference in the average total cost per participant STEP-KOA and AE, divided by the difference in the average effectiveness per participant between STEP-KOA and AE. Bootstrapping of estimates, multiple imputation for missing EuroQoL values, and sensitivity analyses will all be conducted to ensure robustness of our results.