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Confused by clinical research methods? Get a clue!


Thomas Perneger


Clinical research used to be simple, a relaxing diversion after a long day at the surgery. A doctor reviewed the charts of all three patients in his or her practice who suffered from an exotic ailment, computed a proportion or two (“a third died”), took photographs of a Petri dish and of a face rash, added a black bar to cover the eyes of Exhibit 2 – done.

That was then. Today researchers are like wedding planners – they obsess about inclusion criteria, cover up adverse events before anyone notices, lose sleep over budget overruns, and miss out on all the fun. Readers of medical journals are not spared. Articles are full of jargon, and it’s not medical Latin like in the old days. Especially maddening are statistical concepts, disguised as single letters (p, r, kappa), cute metaphors (neural network, bootstrap), or outright lies (normality, significance, error). It’s no wonder doctors only read GetWithIt™ updates anymore! To remedy this situation, Swiss Medical Weekly proposes here an interactive learning tool that will turn you into an instant expert in current research methodology.

To proceed, consider each clue, close your eyes, and let free associations flow. Soon a statistical or epidemiological phrase will occur to you. Do not over-think it. For instance, if the clue is “Final ranking at a beauty pageant?” a valid answer is “Miss classification”. Get it? Misclassification! Don’t worry about sloppy spelling or awkward grammar. Click on “show answer” to verify that you got it right. If you are unfamiliar with the scientific concept, read the comment (if you don’t get the joke, you are on your own).

Let’s play!


1. Final ranking at a beauty pageant

Miss classification

(misclassification) Error in the measurement of a risk factor or a disease, which typically weakens the observed association (misclassification bias)


2. Blueprint for an airport luggage scanner

Case-control design

Type of study in which patients who have a disease are compared to controls who don't


3. Mindset of a helpful doctor

Intention to treat

Analysis of a clinical trial that includes all participants as initially randomised (regardless of actual treatment received)


4. Possibility of your crazy uncle dropping by

Relative risk

Ratio of risks in the exposed and the unexposed


5. Editing a captain's entry

Log transformation

Application of the logarithm function


6. Sigmund Freud's memoirs


Statistical synthesis of the results of several studies that address the same research question


7. Ultimate goal of rehabilitation?

Normal function

Bell-shaped probability density distribution; synonym of Gaussian distribution


8. Slip-up by an evil nerd?

Mean square error

In analysis of variance, the sum of squared differences between observed and predicted values divided by the degrees of freedom


9. They are raised at a nudist camp

Odds of exposure

Odds are a function of a proportion, namely the proportion p divided by its complement (1-p). Exposure is synonym of risk factor.


10. Scale that goes from 0 (sane) to 10 (Hannibal Lecter)

Psycho metric

(psychometric) Related to classic methods for the measurement of unobserved attributes (often psychological variables)


11. Choosing Ronaldo over Messi

Forward selection

Method for selecting covariates for a multivariable model, which starts with the best univariable predictor, then adds the second best, etc.


12. Ask what you will be charged for water or electricity

Cost utility

Type of economic analysis where costs incurred are related to health utility gains


13. Requirement for a double date

Two by two table

Common tool in epidemiology; e.g. tabulation of exposure by outcome


14. Outfitting the troops

Uniform distribution

Distribution that assigns equal probability (or density) to all values on a given interval


15. Telling a friend that she was right to get a divorce?

Split-half validation

Validation method where a model is built on one half of the data and then applied to the other half


16. Urinalysis report


Probabilities of the observed result or more extreme results under the null hypothesis


17. They don’t make the news

Censored events

In time-to-event analysis, observations for which the event of interest has not occurred at the time of analysis


18. Recycling facility for plastics

Composite endpoint

Occurrence of any of several events that are considered equally relevant and therefore combined in a clinical trial


19. Cindy Crawford trying to save on groceries, e.g.

Parsimonious model

Statistical model that includes as few covariates as possible while explaining as much as possible of the outcome


20. It’s all a small window needs

Single blind

A clinical trial in which the patients do not know which treatment they receive


21. List of favourite neighbourhood watering holes

Bar chart

Graph that represents by the height of a bar a characteristic of interest (mean, percentage, etc.) for several subgroups


22. Hanging the flag upside down, e.g.

Standard error

Level of uncertainty of an estimator (i.e., a value obtained from the data) due to the limited sample size


23. Telephone contact of the health insurance department that preapproves health care expenditures

Number needed to treat

Measure of treatment effectiveness; the number of persons that must be treated in order to avoid one clinically relevant event


24. Immature behaviour by the planning committee

Logistic regression

Modelling method used for binary outcome variables


25. Pretending that you have won at roulette, e.g.

Monte Carlo simulation

Computer-based method that explores a phenomenon through the simulated behaviour of repeated samples


26. Iconoclast on drugs

High outlier

Unusually high value of a variable


27. Inside squabble

Within-group variance

In analysis of variance, variability that is not attributable to group membership


28. Dropping a four-letter bomb?


Statistical test used in analysis of variance


29. Two qualities of an effective parental admonishment

Sensitivity and specificity

Ability of a test to correctly identify the diseased (sensitivity) and the non-diseased (specificity)


30. Ultimate pluck

Confidence limit

Upper or lower bound of a confidence interval, which is the range of values of a parameter that are compatible with the observed data


31. When nobody comes to the fashion show

Discrete event modelling

Simulation technique of a complex process that can lead to one or several distinct events


32. Proportion of medical students who choose psychiatry?

Shrinkage parameter

In empirical Bayes estimation, the relative weight given to the overall mean when it is combined with the local estimate


33. Probability of winning the Ig Nobel Prize, e.g.

p <0.001

Low p-value that typically leads to the rejection of the null hypothesis


34. Neatly stacked stolen goods, presented in court

Pyramid of evidence

Hierarchy of scientific evidence based on the trustworthiness of the methods used (meta-analysis of randomised trials at the top and expert opinion at the bottom)


35. What differentiates solitary confinement, county jail and house arrest

Degrees of freedom

Number of independent bits of information that are used to compute a statistic or estimate a model


36. What a wide-receiver should engage in before the pass

Safety monitoring

Procedures for detecting threats to patient safety in a clinical trial


37. Enduring battery life?

Patient autonomy

Ethical principle that gives patients ultimate say in decisions that affect them, including participation in research


38. What the Civil Rights Act of 1964 aimed to do

Recall bias

Systematic error that can affect case-control studies, because the cases may remember their exposure history differently from the controls


39. Parliamentary committee

Representative sample

Sample drawn through a process that guarantees fair representation of the underlying population in the long run (e.g., at random)


40. First date, essentially

Interaction test

Statistical procedure that examines the effect of a variable as a function of another; e.g. a test to compare the effectiveness of a treatment in men versus women


41. Theory of evolution?

Adaptive design

Design of a clinical trial that incorporates future decisions based on accumulated data


42. Like someone who orders Bud Light when Westmalle is on tap

Tripel blind

(triple blind) Triple blinding ensures that the patient, the researcher, and the data analyst are unaware of treatment allocation


43. Important cricket game

Test of significance

Procedure for choosing between two hypotheses (typically “the treatment doesn’t work” vs “the treatment works”) based on observed data


44. Hence the saying “traduttore, traditore”

Translational trials

Studies that test whether basic science advances are applicable to patient care


45. Someone as crazy as you or me

Normal deviate

Normally distributed statistic or observation expressed in standard deviation units


46. Result of neglecting one’s workouts

Marginal conditioning

Treating marginal distributions as fixed when the association between two variables is examined; e.g. the row and column totals are considered fixed when a kappa statistic is computed


47. Tongue tied abbot

Non-informative prior

In Bayesian statistics, the a priori distribution of a parameter that reflects ignorance of its true value


48. Dilemma of the schizophrenic patient?

Multiplicity problem

Proliferation of “significant” results due to type 1 errors when a large number of tests is performed


49. Democracy?

Law of large numbers

Principle that describes the average behaviour of a procedure when it is repeated many times


50. Concession in Amazonia

Forest plot

Graph used in meta-analysis representing the results of several studies, with their confidence intervals, plus the pooled effect


51. Lead a working group at ISO

Direct standardisation

Method for removing confounding, where rates of disease observed in strata of the confounder (e.g., in age groups) are applied to a reference population


52. The custom of putting your boss on your papers, e.g.

Research protocol

Document that describes in detail all procedures to be used in a study


53. Possible causes of mistaken fraternity?

Alpha and beta errors

Type 1 and type 2 errors. The former is the probability of rejecting the null hypothesis when it is true, the latter the probability of accepting the null hypothesis when the alternate is true


54. Its rejection in science leads to acceptance in Nature (and vice versa)

Null hypothesis

Hypothesis of no association or no effect that the researcher hopes to reject.


55. Pissing contest, often

Non-inferiority test

Test of the hypothesis that a treatment is less effective than another by a pre-specified amount


56. Ceremony on the golf course

Link function

Mathematical function applied to the expected value of the outcome variable in generalised linear models; e.g. logarithm function applied to the number of events in log-linear models


57. Prince Philip saying “I do”, e.g.

CONSORT statement

Guideline for the reporting of randomised controlled trials


58. Getting stood up, e.g.

N-of-1 trial

Trial where two treatments are alternated at random within a single patient


59. Ironman deity

Goodness of fit

Measure of the adequacy of a model for a given dataset


60. The sinking of Noah’s ark?

Pairwise deletion

Method for dealing with missing data when correlations are obtained for >2 variables, where each correlation is computed on all available pairs


61. Replying to personal ads on a dating website

Disclosure of interests

Authors’ disclosures of financial or other links with private entities that may bias scientific conclusions


62. Flipping the USB key to make it fit in the slot, e.g.

Two-sided test

Statistical test that leads to rejection of the null hypothesis if the data deviate from the null value in either direction


63. When you wonder if the waiter understood what people wanted to drink next

Second order uncertainty

In modelling, uncertainty about the values of parameters (whereas first order uncertainty concerns values of individual observations)


64. The pride of aesthetes, and the bane of oppressed minorities


Ability of a diagnostic or predictive model to correctly categorise patients with and without a characteristic (e.g., a specific disease)


65. Fil__ng in _he bl_nks

Imputation of missing data

Replacement of missing data by plausible values


66. Checking the authenticity of a wooden relic during the Inquisition

Cross validation

(cross-validation) Method for verifying the properties of a predictive model


67. The number of times you have been fined for speeding or for disorderly conduct

Citation count

The number of times an article is cited in the scientific literature


68. Double take?

Peer review

Evaluation of research articles or protocols by experts in the field to aid the decision to publish the paper or to fund the study


69. What an effective doctor strives for

Good clinical practice

(Good Clinical Practice) Regulations for clinical trials established by the International Conference on Harmonization


70. Plan B?

Residual plot

In regression modelling, differences between observed and predicted values, plotted against predicted values


71. The long and the short of it?

Range of values

Lowest and highest values of a variable


Thank you for playing along!


Disclosure statement

No financial support and no other potential conflict of interest relevant to this article was reported.


Thomas Perneger, MD, PhD
Division of clinical epidemiology
Geneva University Hospitals
6 rue Gabrielle-Perret-Gentil
CH-1211 Geneva