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Ton J Cleophas

Publications and source records attributed to Ton J Cleophas.

5 recordsLinked to original sources
PubMed2004

Clinical trials and p-values, beware of the extremes.

BACKGROUND: In randomized controlled trials, prior to statistical analysis, the data are checked for outliers and erroneous data. Statistical tests are, traditionally, not very good at distinguishing between errors and outliers, but they should be able to point out main endpoint results closer to expectation than compatible with random sampling. OBJECTIVES: To explain from hypothesized and published examples why extreme p-values like p>0.95 and p<0.0001 may indicate that sampling was not completely random. RESULTS: Extreme p-values can be readily observed in recent issues of high-impact journals. A p-value >0.95 literally means that we have a >95% chance of finding a result less close to expectation and, consequently, a <5% chance of finding a result this close or closer. Often in studies a statistical power of 80% is agreed upon, corresponding with a p-value of approximately 0.01. The ultimate p-value may then be a bit larger or smaller. However, a p-value much smaller than 0.01 will be rarely observed, because it would indicate that the study is overpowered. If the p-values can be assumed to follow a normal distribution around 0.01, then we will have a less than 5% chance of observing a p-value of <0.0001. CONCLUSIONS: In randomized controlled trials, main endpoint p-values larger than p=0.95 will be rare, because they would indicate similarities closer than compatible with a normal distribution of random data samples. Also very low p-values like p<0.0001 will be rarely encountered, because it would mean that the trial was overpowered and should have had a smaller sample size. It would seem appropriate, therefore, to require investigators to explain such results and to consider rejecting the research involved. So far, in randomized controlled trials the null-hypothesis is generally rejected at p<0.05. Perhaps we should consider rejecting the entire study if the main endpoint p-values are >0.95 or <0.0001.

Area Under Curve↗
PubMed2003

Age-related decline in autonomic control of blood pressure: implications for the pharmacological management of hypertension in the elderly.

Autonomic control of blood pressure appears to decline with age giving rise to an increased risk of orthostatic hypotension and major hypotensive reactions to antihypertensive drugs. In the past few years, many workers have assessed autonomic function in the elderly and sometimes found controversial results. Baroreflex sensitivity, as measured by the steepness of the heart rate/mean pressure curve, decreases with age. However, this phenomenon does not correlate well with orthostatic impairment. Sympathetic dysfunction might be more responsible for syncopal symptoms in the elderly, a finding supported by the fact that elderly with orthostatic symptoms never collapse within a few seconds, but do so after 1 or more minutes of standing. However, the results of sympathetic function testing in the elderly indicate that sympathetic function in most elderly is not impaired and that sympathetic activity, as measured by circulating levels of catecholamines, is usually increased rather than decreased. In various populations with increased sympathetic activity, but not in the elderly, beta-adrenoceptor antagonists (beta-blockers) have been demonstrated to cause pressor effects, presumably due to alpha-adrenoceptor-mediated vasoconstriction unopposed by beta-receptor-mediated vasodilation. In the past year, large studies have been completed indicating that the same is true for the elderly, and that the depressor effect on pulse pressure upon standing in this category of patients can be offset and turned into a pressor effect by long-term beta-blocker treatment. This phenomenon could not be demonstrated with non-beta-blocker antihypertensive drugs, including ACE inhibitors, calcium channel antagonists, diuretics and angiotensin II receptor antagonists. In elderly patients beta-blockers may, therefore, be the most appropriate antihypertensive agents as they protect the elderly from orthostatic impairment.

Age Factors↗
PubMedDate not supplied

Clinical trials: Renewed attention to the interpretation of the P values--review.

The P values tell us the chance of making a type I error of finding a difference where there is none. In the 1970s, exact P values were laborious to calculate and were generally approximated from statistical tables, in the form of P < 0.01 or 0.05 < P < 0.10, etc. In the past decades with the advent of computers, it became easy to calculate exact P values such as 0.84 or 0.007. The cut-off P values have not been completely abandoned, but broader attention is given to the interpretation of the exact P values. This article reviews standard and renewed interpretations of P values. (1) Standard interpretation of cut-off P values such as P < 0.05: The null hypothesis of no difference can be rejected on the limitations/assumptions that we have up to a 5% chance of a type I error of finding a difference where there is none, we have 50% chance of a type II error of finding no difference where there is one, the data are normally distributed, they follow exactly the same distribution as that of the population from which the sample was taken. (2) A common misunderstanding of the P value: It is actually the chance that the null hypothesis is true and consequently that a P > 0.05 indicates a significant similarity in the data. P > 0.05 may indeed indicate similarity. However, a study sample too small or study design inadequate to detect the difference must be considered. (3) Renewed interpretations of the P values: Exact P values enable more refined conclusions from the research than cut-off levels. Instead of concluding significantly yes/no, we are able to consider levels of probabilities from very likely to be true to very likely to be untrue. Very large P values are not compatible with a normal gaussian frequency distribution; very small P values do not completely confirm prior expectations. They must be scrutinized and may have been inadequately improved.

Clinical Trials as Topic↗