Design of experiments Created 2026-10-07 Updated 2026-10-14
Design of experiments chooses experimental units, treatments, replication, blocks in experimental design and randomization so that scientifically useful treatment contrasts can be estimated with meaningful standard errors. Allocation determines which measurements supply independent treatment information.
Eligibility criteria for a clinical trial Created 2026-10-07 Updated 2026-10-14
Eligibility criteria specify which individuals may enter a clinical trial, defining its enrolled population and excluding individuals for whom the intervention or measurements are unsuitable. Screening applies those criteria before randomization. The treatment comparison's external validity depends on how this population relates to the population of interest.
Germination assay 2026-10-14
A specified test for germination, recording the endpoint, conditions and observation window. For a proposed red/far-red light test, use randomization to allocate one seed lot to darkness, red, red then far-red, and red then far-red then red. Match hydration, temperature, handling and elapsed time before counting; use sham waiting periods to equalize schedules. Use dish replication, retain the dark scientific control, and record radicle emergence using an observation procedure that does not itself provide an uncontrolled light treatment. This is a proposed design, not a claim about the 1952 paper's randomization or replication.
As an original hypothetical counting example, begin with seeds in one dish. Suppose 12 first meet the radicle endpoint by 24 hours, eight additional seeds by 48 hours, and four additional seeds by 72 hours. These invented event counts giveand cumulative sample proportions , and . The 48-hour increment is , not ; the latter includes earlier events. Counting the same emerged radicle again at each inspection would inflate the total. These numbers illustrate bookkeeping, not biological rates or treatment effects.
With a fixed denominator and irreversible classification of the first endpoint event, the set counted at an earlier inspection is a subset of the set counted later. Hence and cannot decrease. This short proof applies to cumulative germination counts even if a later seedling dies. A count of currently surviving seedlings has a different definition and can decrease.
For treatment comparisons, the dish may be the experimental unit: seeds in the same dish share conditions. Forty seeds in one dish do not supply forty independent dish replicates. Report the sample size, replication, endpoint time and denominator; a sample proportion by a deadline measures this assay's outcome, not an unconditional fraction with seed viability.
Informed consent Created 2026-10-07 Updated 2026-10-13
Informed consent is voluntary agreement after receiving and understanding relevant information about an intervention or participation in research. In a clinical trial, the participant is informed about the study procedures, potential benefits and risks, alternatives and the option to decline or withdraw. Consent precedes randomization.
Intention-to-treat analysis Created 2026-10-07 Updated 2026-10-14
An intention-to-treat analysis compares participants according to their randomized assignment, retaining that assignment even when they do not use the assigned intervention. Its causal effect is the effect of assignment under the study's actual adherence pattern, rather than the effect of perfect adherence. Randomization protects this comparison from baseline confounding; missing data can still require assumptions or additional analysis.
Nested measurements 2026-10-18
Nested measurements are responses grouped inside larger units, with each measured object belonging to just one such unit. Three leaves within each pot give nested measurements; repeatedly reading one leaf gives another level of repetition. Either can yield clustered data. A common random effect can describe the shared influence of the containing experimental unit.
For the constructed pot example, label treatments by , pots within each group by , and leaves within each pot by . Consider the statistical modelHere is a leaf length, is its group expected value, is a pot random effect, and describes remaining variation among leaves and measurement error. Assume that all pot random effects are mutually independent, all remaining errors are mutually independent, and the two collections are independent of one another and of the randomization. These are explicit modelling assumptions, conditional on the assigned treatments; no normal distribution assumption is needed for the following variance calculation.
Two distinct leaf measurements in one pot share . Their covariance is , their individual variance is , and their intraclass correlation coefficient isMeasurements from different pots have zero covariance and are independent under the stated statistical model. Statistical independence therefore concerns the whole response structure, not just the fact that the measured leaves are different objects.
Past exam of the mathematics course of the University of Cambridge 2001 iii Paper 28 4 a Solution Created 2026-10-03 Updated 2026-10-14
The survival estimates favor the new treatment at the two reported times, with absolute survival differences at two years and at five years. These point differences alone do not establish efficacy. Randomization supports a causal comparison of the treatment assignments, but sampling variance, censoring, follow-up, protocol adherence and the prespecified endpoint still matter. One should not infer a statistically established benefit merely from two larger estimates.
A Kaplan–Meier estimator iswhere is the risk set and the event count. Its uncertainty depends on the actual risk sets, not just the initial group size. The Greenwood formula estimatesWithout the missing survival tables one cannot calculate these standard errors or the uncertainty of the group difference. In particular, replacing the estimator variance by the variance of an uncensored binomial proportion would generally be wrong.
I would advise presenting both curves with numbers at risk and confidence intervals, checking independent censoring, and reporting a prespecified overall comparison plus an effect estimate and interval. For an unadjusted log-rank test, write and . Its hypergeometric null variance isTerms with no possible variation contribute zero. This compares the entire event history rather than selecting two arbitrary times, uses the available risk sets, and avoids choosing favorable time points after examining the curves. It is especially effective under proportional hazards. Crossing curves can make a log-rank comparison insensitive; a prespecified restricted mean survival time difference or another suitable time-varying analysis may then be more informative. An overall comparison does not make a clinically important prespecified time-point contrast invalid.
The Kaplan–Meier median survival time is the first event time at which . Monotonicity of the reported estimates impliesIf the new-treatment curve never reaches one half during observed follow-up, its median is not estimable from that curve. The exact crossing times cannot be reconstructed from two survival probabilities: the standard curve could first cross at three or at four years and still have the same values at two and five years. The point estimates suggest benefit, but the evidence and exact medians require the missing event/censoring tables. Neither a conclusive agreement nor a conclusive rejection of benefit is justified from these numbers alone.
Past exam of the mathematics course of the University of Cambridge 2004 iii Paper 38 4 e Solution Created 2026-10-03 Updated 2026-10-14
A trial can be well powered for a common reconviction outcome and poorly powered for a small difference in rare deaths. Failure to obtain a significant mortality comparison would not show that the treatments have equal safety. Participants' overall welfare cannot be reduced to reconviction alone: a decrease in that outcome must be weighed against possible loss of life.
Ethical randomization depends on clinical equipoise about the overall benefit-risk balance. Participants need voluntary informed consent that explains the uncertainty and possible mortality tradeoff; a criminal-justice setting demands particular care about coercion. The design should ascertain serious outcomes completely, use independent trial safety monitoring with prespecified stopping rules, and seek pooled safety evidence when an adequately powered mortality comparison needs collaboration. These principles are consistent with the research protections described in the Declaration of Helsinki.
A smaller efficacy trial is not automatically unethical, but deliberately avoiding adequate safety information is not a justification for it. A limited initial study needs a defensible scientific purpose, proportionate safeguards and an explicit plan for resolving serious-harm uncertainty; if evidence establishes an unfavorable net balance, continuing randomization merely to improve precision would not be justified.
Past exam of the mathematics course of the University of Cambridge 2005 iii Paper 44 4 a Solution Created 2026-10-03 Updated 2026-10-14
A court-based randomized controlled trial would assign eligible offenders between the two sentencing policies using randomization, ideally stratified by court and important prespecified risk factors. With allocation concealment, the next assignment cannot be selected to suit an offender's prognosis. Baseline characteristics, both recorded and unrecorded, are balanced in distribution rather than confounded with judges' sentencing preferences. This makes a comparison of outcomes interpretable as a causal effect of assignment, subject to complete and comparable follow-up, whereas separate historical cohorts can differ in severity, social circumstances or calendar period.
The commission should compare both specified outcomes over the same 360-day period from sentencing, using an intention-to-treat analysis. An offender initially assigned community service remains in that group even if the order is later revoked and prison follows. Revocation is part of the policy's consequences; restricting the comparison to completers would select on a post-assignment outcome and lose the protection of randomization.
Within-court individual randomization also provides an objective allocation procedure and valid uncertainty estimates. It does not guarantee identical characteristics in a particular finite sample or eliminate loss to follow-up, unequal outcome ascertainment or limited generalizability. Eligibility, genuine uncertainty about the two policies, and a feasible authorized allocation mechanism would need agreement before the trial. If whole courts rather than individuals were assigned, that would be a cluster-randomized trial and its correlation structure would require a different sample size calculation.
Past exam of the mathematics course of the University of Cambridge 2007 iii Paper 46 1 c Solution Created 2026-10-03 Updated 2026-10-14
Let be attendance totals and the observed person-time at risk. Under independent Poisson distributions for the totals, the estimated incidence rate ratio is . Treating the exposures as known, the supplied large-count approximation, or the delta method, givesIndependence adds the log-count variances, while fixed exposure terms add no variance. Form the normal confidence interval on the log scale and exponentiate:This specifies the calculation without evaluating it. Individual randomization makes a child the assignment unit, but an independent Poisson count model remains an additional assumption about outcomes, not a consequence of randomization alone.
Past exam of the mathematics course of the University of Cambridge 2009 iii Paper 41 1 a Solution Created 2026-10-03 Updated 2026-10-14
Use separate randomization lists for women with and without a self-reported history of depression. Within each stratum, the central service could assign intervention and control in a ratio using randomly permuted blocks, preferably with concealed and varying block sizes. This is stratified randomization; the internet service can retain allocation concealment because the recruiting staff do not know the next assignment.
History is plausibly prognostic for the outcome. Keeping its distribution similar between arms reduces the risk of a chance imbalance in that important baseline factor and can improve precision. It also allows a comparison within each history stratum. Stratification does not guarantee balance of every other covariate, and staff must not be allowed to choose assignments. The regression model can retain history as a baseline covariate, respecting the design.
Past exam of the mathematics course of the University of Cambridge 2009 iii Paper 41 1 f Solution Created 2026-10-03 Updated 2026-10-14
There was no clear documentation of initiation for women, givingThese women may not have received the intervention, although missing documentation is not proof that no contact occurred. Documentation of initiation also does not establish completion or full adherence.
Under intention-to-treat analysis, women retain their randomized arm regardless of actual uptake. Removing nonadherent women would condition on a post-randomization characteristic and could destroy the comparability created by randomization. The resulting estimand is the effect of offering the intervention under the trial's actual adherence pattern. Keeping nonadherent women in their arm does not itself solve missing-outcome problems: the reported 12-week denominators are smaller than the randomized totals, so the outcome analysis still needs an appropriate strategy and assumptions for losses to follow-up.
Past exam of the mathematics course of the University of Cambridge 2010 iii Paper 34 1 g Solution Created 2026-10-03 Updated 2026-10-14
The groups were not formed by randomization. Their background health, access to care, clinic, country and reasons for selecting a delivery method can predict both the method and the outcome, creating confounding and selection bias. Moreover, the label describing the reference delivery may be determined after labour: patients whose attempted nonoperative delivery develops a complication can move into an operative category, leaving a selected uncomplicated reference group. Comparing intended strategies would avoid treating this post-baseline classification as a baseline assignment.
A useful comparison would therefore align eligibility and follow-up time, compare intended delivery strategies among patients genuinely eligible for both, and account for sufficient pretreatment predictors. Logistic regression cannot create comparable patients where the positivity assumption fails or remove unmeasured confounding.
Past exam of the mathematics course of the University of Cambridge 2012 iii Paper 41 1 a i Solution Created 2026-10-03 Updated 2026-10-07
Screening applies the eligibility criteria for a clinical trial before treatment allocation. It identifies the population to which the comparison pertains and excludes individuals for whom the intervention or measurements are unsuitable. Recording potentially eligible individuals also helps describe recruitment and assess external validity. It should precede randomization so eligibility is not decided using knowledge of the allocated treatment.
Past exam of the mathematics course of the University of Cambridge 2012 iii Paper 41 1 a iv Solution Created 2026-10-03 Updated 2026-10-07
Randomization makes assignment independent of the participants' pre-existing potential outcomes, giving an unbiased comparison of allocation groups under the usual trial assumptions. It therefore protects against baseline confounding, including from unmeasured factors, and supplies an assignment distribution for inference. Allocation concealment protects this step from recruitment decisions based on the upcoming assignment. It does not guarantee exact balance in every realized sample.
Past exam of the mathematics course of the University of Cambridge 2013 iii Paper 35 2 d Solution Created 2026-10-03 Updated 2026-10-07
Consider learning and memory of the maps. Repeating an identical map can improve later scores through recall rather than the assigned program, and a skill learned using one program can transfer to another. Provide comparable familiarization before recording responses and use new, difficulty-matched maps on later afternoons. If all volunteers face the same map on a given afternoon, common map difficulty is absorbed by the afternoon block.
The balanced transitions in the proposed row-column design help with first-order carryover effects, but general practice, higher-order memory and program-dependent learning may still require an explicit interaction term or carryover effect in the analysis. Merely applying randomization to treatment labels cannot make these effects disappear.