The minimal clinically important difference raised the significance of outcome effects above the statistical level, with methodological implications for future studies

OBJECTIVE To illustrate and discuss current and proposed new concepts of effect size (ES) quantification and significance, with a focus on statistical and clinical/subjective interpretation and supported by empirical examples. STUDY DESIGN AND SETTINGS Different methods for determining minimal clinically important differences (MCIDs) are reviewed, applied to practical examples (pain score differences in knee osteoarthritis), and further developed. Their characteristics, advantages, and disadvantages are illustrated and discussed. RESULTS Empirical score differences between verum and placebo become statistically significant if sample sizes are sufficiently large. MCIDs, by contrast, are defined by patients' perceptions. MCIDs obtained by the most common "mean change method" can be expressed as absolute or relative scores, as different ES parameters, and as the optimal cutoff point on the receiver operating characteristic curve. They can further be modeled by linear and logistic regression, adjusting for potential confounders. CONCLUSION Absolute and relative MCIDs are easy to interpret and apply to data of investigative studies. MCIDs expressed as effect sizes reduce bias, which mainly results from dependency on the baseline score. Multivariate linear and logistic regression modeling further reduces bias. Anchor-based methods use clinical/subjective perception to define MCIDs and should be clearly differentiated from distribution-based methods that provide statistical significance only

Diagnosis and course of affective psychoses: was Kraepelin right?

Kraepelin's basic attitude to the classification of psychoses was data-oriented and flexible. In his latter years he was close to revising his own celebrated dichotomy between manic-depressive insanity and dementia praecox in order to take account of a large group of intermediate psychoses, which today are called schizo-affective. His concept of a continuum from healthy to ill has stood the test of time and corresponds to modern epidemiological findings. Kraepelin's unitarian concept of manic-depressive insanity did not survive. It was differentiated and broken down into several subgroups, and a proportional diagnostic spectrum with a continuum from mania via bipolar disorders to depression has recently even been proposed. Bipolar disorders would in that case be comorbid disorders of mania plus depression. In contrast to Kraepelin's unitarian view the long-term prognosis of subgroups of mood disorders varies considerably. Overall it is nevertheless astonishing how much of Kraepelin's legacy has survive

Concurrent psychiatric comorbidity and multimorbidity in a community study: gender differences and quality of life

This study analysis of a community cohort at the age of 35 focused on the effects of gender and multimorbidity on quality of life and subjective distress. Consistent with an earlier analysis, quality of life decreased with increasing numbers of concurrent psychiatric diagnoses. Women generally reported lower quality of life and higher distress than men. Relative to men, well-being in women was subject to more diagnostic (alcohol abuse/dependence, depression, generalized anxiety disorder, bulimia) and social influences (partner, promotion). The same factors predicted women's psychological and physical well-being, indicating a more holistic experience in women. Men's physical well-being did not correlate with any of the diagnostic or social variables measure

The Zurich Study XXIV: Structural and emotional aspects of childhood and later psychopathology

A Swiss cohort interviewed four times between ages 20 and 30 years reported on a structural aspect of childhood (separation from parents) and emotional aspects (family strain, childhood behavioral and emotional problems). These data were connected with DSM-III-R diagnoses of anxiety and depression, SCL-90R scores (all repeatedly ascertained) and with Freiburg Personality Inventory results at age 30 years. Adult psychopathology, personality deviations, and negative affectivity were not connected with early or later separation, but with a report of family strain and childhood disturbances. As variables associated with later psychiatric symptoms and disorder, interpersonal and subjective aspects of childhood outweigh the fact of separation from parent

Epidemiological and clinical aspects of bipolar disorders: controversies or a common need to redefine the aims and methodological aspects of surveys

Data from surveys of large samples showed the lifetime prevalence rates of bipolar disorder around 1.5%. A main question is whether the low prevalence rates of bipolar disorders are not an artefact of the over-diagnosis of depression and under-diagnosis of bipolar-II. Analysis of the clinician's logical inferential diagnostic process, confirms that the patient does not represent the sole source of useful information because many patients do not experience hypomania as distress but rather as recovery from depression or as a period during which they felt truly well. Epidemiological data are derived from interviews carried out by lay staff which only reflect the patient's point of view. The clinical monitoring study carried out alongside the ESEMED project found for the diagnosis of mood disorders, a Kappa agreement (versus clinical interview) which ranged from 0.23 in Spain to 0.49 in France. If we consider exactly what a Kappa of 0.4 implies for a disorder with an "identified" prevalence rate of 2%, we discover that the prevalence rate may have been under-diagnosed approximately 1.5-fold, so 67% of cases may not have been identified and 50% of the identified cases may be false positives. It is legitimate to surmise that the prevalence reported by recent (extremely costly) epidemiological surveys may be doubtful. Which direction should epidemiology take in dealing with the serious matter of bipolar disorders? Recently, some community surveys were carried out in the USA using the Mood Disorder Questionnaire. In the ensuing debate, one side claimed that the instrument was scarcely accurate when used in the general population, gave rise to numerous false positives and that the high prevalence reported was therefore a mere artefact. The other side defended the results reported by the research studies, on the basis that "positive" cases were homogeneous with regard to the high level of subjective distress, low social functioning and employment and with the high recourse to health care structures. It is quite probable that the problem lies at the root of the matter, in the definition of the gold standard. In the present state of our knowledge on course and response to treatment, the current diagnostic thresholds applied for mixed states and hypomanic episodes seem to be unsatisfactory. It is inconceivable that the diagnostic gold standard should be determined only on the basis of a structured interview of patients alone. But unless there is clinical consensus on the diagnostic threshold for hypomania and mixed states, there can be no consensus on the findings of epidemiological research

Multidimensional minimal clinically important differences in knee osteoarthritis after comprehensive rehabilitation: a prospective evaluation from the Bad Zurzach Osteoarthritis Study

OBJECTIVE To determine minimal clinically important differences (MCIDs) for improvement and worsening in various health dimensions in knee osteoarthritis under conservative therapy. METHODS Health, symptoms and function were assessed by the generic Short Form 36 and the condition-specific Western Ontario and McMaster Universities Osteoarthritis Index in n=190 patients with knee osteoarthritis before and after comprehensive rehabilitation intervention (3-month follow-up). By means of construct-specific transition questions, MCIDs were defined as the difference between the 'slightly better/worse' and the 'almost equal' transition response categories according to the 'mean change method'. The bivariate MCIDs were adjusted for sex, age and baseline score to obtain adjusted MCIDs by multivariate linear regression. They were further standardised as (baseline) effect sizes (ESs), standardised response means (SRMs) and standardised mean differences (SMDs) and compared with the minimal detectable change with 95% confidence (MDC95). RESULTS Multivariate, adjusted MCIDs for improvement ranged from 2.89 to 16.24 score points (scale 0-100), corresponding to ES=0.14 to 0.63, SRM=0.17 to 0.61 and SMD=0.18 to 0.72. The matching results for worsening were -5.80 to -12.68 score points, ES=-0.30 to -0.56, SRM=-0.35 to -0.52 and SMD=-0.35 to -0.58. Almost all MCIDs were larger than the corresponding MDC95s. CONCLUSIONS This study presents MCIDs quantified according to different methods over a comprehensive range of health dimensions. In most health dimensions, multivariate adjustment led to higher symmetry between the MCID levels of improvement and worsening. MCIDs expressed as standardised effect sizes (ES, SRM, SMD) and adjusted by potential confounders facilitate generalisation to the results of other studies