Rough draft.This research track is under review with Dr. Atit's lab. Content and sequence may still change.
The Baby Mateo Case
Experimental Design domainBiomedical Innovations (BI)Lesson 14 of 20Your seat: Principal Investigator (with the team biostatistician)
The TOPS Trial: How Surgeons Tested the Best Time to Repair a Palate
Discovery question
How did one real randomized trial test the best timing of surgery, and what exactly did its main result prove?
💡 A trial earns trust by naming one in advance and reporting its effect with uncertainty; a and its 95% say more than a bare yes or no.
The plan
Prerequisite check
Before this page, you should know
- A assigns patients to treatments by a chance process, and it is the strongest design for a question about which treatment causes a better outcome.
- Randomization spreads every trait, even traits never measured, roughly evenly across groups, so any difference in outcome is believably due to the treatment.
Today's new idea is only
A trial earns trust by naming one in advance and reporting its effect with uncertainty; a and its 95% say more than a bare yes or no.
Learn first
What you will learn
Goal: Walk a real RCT from question to result, and read its (, 95% CI, p-value) to state what it proved and what it did not.
Know by the end
- TOPS compared repair at 6 months versus 12 months in 558 infants across 23 centers in five countries, excluding syndromic and severely delayed children.
- The was at 5 years; rates were 8.9% (21 of 235) at 6 months and 15.0% (34 of 226) at 12 months.
- The reported effect was 0.59, 95% 0.36 to 0.99, P = 0.04, so earlier repair lowered the chance of the speech problem, but the CI nearly touches the no-difference value of 1.0.
- TOPS did a planning about 292 children per group for 80% power at alpha 0.05; recruitment fell a bit short, which lowered power, and generalizability is limited to medically fit, isolated, non-syndromic cases.
Learn first
Model: The TOPS design and its headline result
From the TOPS trial report: the two arms repaired an at 6 months versus 12 months. The trial enrolled 558 infants with isolated cleft palate across 23 centers in Brazil, Denmark, Norway, Sweden, and the United Kingdom; infants with syndromes or severe developmental delay were excluded. A web-based algorithm randomly assigned infants 1:1, stratified by surgeon and extent. Every surgeon used the same (Sommerlad) technique. The speech assessors who scored the children at age 5 worked at a central facility, unaware of each child's timing group. The was at 5 years of age, the palate failing to close off the nose during speech.
The headline result: 21 of 235 children repaired at 6 months had the speech problem (8.9%), versus 34 of 226 repaired at 12 months (15.0%). Reported effect: 0.59, 95% 0.36 to 0.99, P = 0.04. Before the trial, the team planned about 292 children per group for 80% power at a significance level of 0.05; recruitment was hard, and the trial ended a bit below that target.
Do the work
Explore (work the model before reading on)
- What were the two treatments being compared, and at what single age was the main outcome measured?
- Which group had the lower rate of the speech problem, and by how many percentage points?
- A of 0.59 means the 6-month group's risk was about 59% of the 12-month group's risk. In plain words, did earlier surgery raise or lower the chance of the speech problem?
- The 95% CI ran from 0.36 to 0.99 and the no-difference value for a is 1.0. Since the interval stops just below 1.0, is the result statistically significant, and how confident does that narrow miss make you?
- TOPS deliberately excluded children with syndromes. Predict one reason for that and one limit it puts on who the result applies to.
The plan
Guided notes
1
Primary outcome and the risk ratio
Model start: A trial names one before it starts, then lives or dies by that result; TOPS named at 5 years. Picking it ahead of time stops a team from fishing and reporting whichever result looks best.
- A of 1.0 means ____ (no difference / a big difference); below 1.0 means the treated group had ____ (lower / higher) risk.
- TOPS got 0.59, so early repair ____ the chance of the speech problem.
- For a ratio, if the 95% excludes 1.0 the result is statistically ____; TOPS reported 0.36 to 0.99, which just barely excludes 1.0.
2
Power and generalizability
- A is the homework done ____ a trial: how many patients are needed so a real effect is likely to show up.
- TOPS planned roughly ____ per group for 80% power; recruitment fell short, which lowered power.
- Generalizability asks who the result applies to; TOPS studied medically fit, ____ (isolated / syndromic) in well-resourced centers, so its answer is strongest for children like that.
Explore
Reading the Research
What to read
Read the title and the abstract only, not the whole paper. Gamble et al. 2023, Timing of Primary Surgery for Cleft Palate (TOPS trial, NEJM)
Why this source matters
This is the published evidence behind today's idea: A trial earns trust by naming one in advance and reporting its effect with uncertainty; a and its 95% say more than a bare yes or no.
Words to unlock first
primary outcomerisk ratioconfidence intervalpower calculationgeneralizability
Reading moves
- Skim the title and abstract first to get the gist.
- Circle the one sentence that states the main claim.
- Box the evidence the authors give for that claim.
- Mark one sentence that confuses you, and move on.
Stop point
You do not need the methods or statistics yet. If a sentence is about lab technique or math you have not learned, mark it and skip it.
Your output
Write one claim-evidence sentence: what this source claims, and the one piece of evidence that backs it up.
Where this fits
Tested on (Ohio WebXam)
Genetics of Disease · 072130
PLTW lesson
MI · Experimental Design domain · Reading a real RCT: primary outcome, risk ratio, confidence interval, power, generalizability
WebXam domain
Bio-Molecular Technology
Evidence to produce
Your cleft team is deciding when to schedule a palate repair, and a parent asks whether there is real evidence for the timing. Using only the model, write a three-sentence brief: (1) state the question TOPS asked and the two ages compared; (2) state the primary outcome result in plain words, using the two percentages and the direction of the risk ratio; (3) state one honest limit (whom the result applies to, or that the confidence interval came close to no difference).
Lab / skill
Biomedical Innovations (BI) · AP Biology
Words
Vocabulary (the same words your classes use)
Explore
Vetted readings for this lesson
The plan
Track your progress today
Check these off as you work through the lesson, then submit. This tells Mr. Mendoza how you're doing so he can help the class. It does not replace turning in your producible.
Use the code Mr. Mendoza gave you, not your name. Saved on this device.
Check off as you finish
- Read the Model and answered the Explore questions.
- Filled in the guided notes in my own words.
- Defined the new vocabulary with an example.
- Built the producible: Your cleft team is deciding when to schedule a palate repair, and a parent asks whether there is real evidence for the timing. Using only the model, write a three-sentence brief: (1) state the question TOPS asked and the two ages compared; (2) state the primary outcome result in plain words, using the two percentages and the direction of the risk ratio; (3) state one honest limit (whom the result applies to, or that the confidence interval came close to no difference).
- Wrote my Claim, Evidence, and Reasoning exit ticket.
Pick your period and code first.
Check yourself
Exit ticket (Claim, Evidence, Reasoning)
- Claim: Repairing an at 6 months rather than 12 months (lowers / raises / does not change) the chance of at age 5.
- Evidence: Cite the two percentages (8.9% vs 15.0%) and the with its 95% CI (0.59, 0.36 to 0.99).
- Reasoning: Explain how the excluding 1.0 lets us call the difference real, and name one group the result may not apply to.
How this is graded (rubric)
For: Your cleft team is deciding when to schedule a palate repair, and a parent asks whether there is real evidence for the timing. Using only the model, write a three-sentence brief: (1) state the question TOPS asked and the two ages compared; (2) state the primary outcome result in plain words, using the two percentages and the direction of the risk ratio; (3) state one honest limit (whom the result applies to, or that the confidence interval came close to no difference).
| Criterion | Proficient | Developing | Beginning |
|---|---|---|---|
| Complete | Every required part of the artifact is present and filled in. | Most parts are present, but one is missing or left blank. | Several parts are missing. |
| Accurate | The science and data are correct and match the evidence. | Mostly correct, with a small factual slip. | Key science or data is wrong. |
| Scientific reasoning (CER) | States a claim, backs it with specific evidence, and explains the reasoning. | Has a claim and evidence, but the reasoning is thin or missing. | Gives an answer with no evidence or reasoning. |
| Professional communication | Clear, organized, and labeled the way a clinician or scientist would write it. | Readable but disorganized or missing labels. | Hard to follow. |
| Submitted | Turned in the right way (Schoology for routine work) and confirmed. | Turned in, but in the wrong place or unconfirmed. | Not turned in. |
How the model answer scores against this rubric
- CompleteProficient: Nothing is left blank: the model fills every part of "Your cleft team is deciding when to schedule a palate repair, and a parent asks whether there is real evidence for the timing. Using only the model, write a three-sentence brief: (1) state the question TOPS asked and the two ages compared; (2) state the primary outcome result in plain words, using the two percentages and the direction of the risk ratio; (3) state one honest limit (whom the result applies to, or that the confidence interval came close to no difference).".
- AccurateProficient: Every number and claim matches the case evidence.
- Scientific reasoning (CER)Proficient: It names a claim, cites the specific evidence, and explains the reasoning, not just the answer.
- Professional communicationProficient: It is organized and labeled like a real chart note.
- SubmittedProficient: It would be turned in on Schoology and confirmed.
Explore
Where this leads: careers
Biostatistician Clinical Researcher Speech-Language Pathologist
What's next: TOPS rested on one judgment for every child: did this 5-year-old's speech sound right, or was it nasal and unclear? But good speech is not a number a machine prints out. How do you actually measure something as fuzzy as speech, fairly and the same way for hundreds of children? We chase that next time.
The Fairest Test: How to Compare Two Treatments in Real ChildrenHow Do You Measure Something as Fuzzy as Speech?