During the three years over which I had the good fortune of heading the extensive medical department at St. Hedwig’s Hospital in Berlin, I used every opportunity to look for satisfactory methods for therapeutic investigation. The results presented here are as yet incomplete. Never the less I am publishing them because it seems to me that a change in the situation as it stands cannot bear postponment any longer.
Bonn, April 1932
I. Comparison as the basis of therapeutic investigation ….
Observation of the course of the individual patient. – Preliminary observation: uniformity, continuity and direction, constancy of the patient’s course. p. 1. – Past medical history and preliminary observations. p. 4. – Sum of experiences pertaining to duration and result, comparability of cases; epidemiological fluctuations (alternation scheme): bacteriological differentiation. p. 4. – Number of cases, duration and type of observation. p. 5. – Superiority of the method of preliminary observation. p. 5. – Uniformity of the spontaneous course of the disease, uniformity of the influenced course of the disease (homogeneity of the results). p. 5. – Quality of the criteria: Range of error, frequency of the practicability , unequivocalness, significance, possibility of numerical description of the methods. p. 6. – Objective criteria. p. 7. – Subjective criteria: assessment, unknown (today, ‘blinded’) trial design. p. 7.
II. Co-factors in therapeutic research….
The clearly defined experiment. p. 9. – Mental alterations. p. 10. – Physical complications: unavoidable complications, intercurrent and complicating illnesses. p. 11. – Avoidable complications, competition of medications (Konkurrenz der Heilmittel) [today this would probably referred to as “drug interactions”]. p. 11. – Correction of the co-factors: Elimination of certain observations, omission of entire test series (Versuchsreihen). p. 12.
III. Quantitative therapeutic investigation….
Requirements for the basis of comparison: Observation of the course of the illness in one and the same individual. p. 14. – Similarity of the living conditions. p. 14. – Continuity of the course of the illness. p. 14. – Constancy of the course of the illness; stable and unstable constancy. p. 14. – Standards of the quantitative investigation: absolute measurement. p. 15. – Relative measurement; dose and efficacy; Dosis efficiens minima. (minimum effective dose). p. 15.
IV. Statistical methodology….
The pure case and the statistical mass. p. 16. – The law of large numbers. p. 17. – Homogeneity of the statistical mass. p. 17. – Categorizing the mass into groups. p. 17. – Table, series, graph, bar chart. p. 18. – Selecting the standard. p. 18. – The statistical means. p. 19. – Statistical dispersion. p. 21. – The statistical proportions. p. 22.
V. Assessment of therapeutic results with help of the calculus of probability..
Application of the rules of mathematical probability to medical-therapeutic problems. p. 24. – The significance of absolute numbers of probability in the assessment of an disease according to its outcome; the numbers 0 and 1 in mathematical probability and the negative value of probability. p. 24. – Probability in the assessment of disease according to its course by means of graphs or periods. p. 28. – Relative probability. p. 31. – The advantages of the calculus of probability. p. 35.
VI. Therapeutic research as a science. Criticism of the current situation….
The deductive origin of therapeutic research. p. 37. – Hypothesis and thesis. p. 38. – Neglect of methodology in research. p. 38. – Incomplete publications. p. 39.
VII. Specific methodology for therapeutic investigations….41
1. Heart failure and dynamic heart medication….41
2. Angina pectoris….48
5. Basedow’s disease….58
6. Chronic joint illnesses and neuralgias….64
7. Gastric ulcer….67