Research questions that cannot or that can only with difficulty be investigated in RCTs
| Topic | Reason |
|---|---|
| Research questions that in certain circumstances cannot be investigated in RCTs | |
| Life-threatening intervention, for example, intervention with high early treatment-related mortality | Allocation to intervention group endangers life |
| Certain second-line interventions reserved for refractory patients that did not respond to first-line standard therapy | Ultimo ratio and therefore no control group by definition. Example: Haematopoietic stem cell transplantation from unrelated versus related donors for patients with acquired severe aplastic anaemia |
| Pregnant women | Ethical concerns against inclusion in experiments |
| Infants | Ethical concerns against inclusion in experiments |
| Interventions that have been shown to produce a dramatic effect | The magnitude of benefit of one particular intervention such as insulin to treat diabetes mellitus would render any intervention a neglect of healthcare if insulin would be omitted unless the new treatment does also have a dramatic effect |
| Lack of consent to participate | Cheating persons is not legal |
| Studies that do not comply with the Declaration of Helsinki | The set of ethical principles regarding human experimentation is regarded as the cornerstone document of human research ethics |
| Research questions that can with difficulty be investigated in RCTs | |
| Rare adverse events and other rare safety outcomes | Number of study participants is too low |
| Allocation of alternative interventions is dominated by patients’ preferences | Treatment group is chosen by a patient because of specific expectations of effectiveness, adverse events or health-related quality of life |
RCTs, randomised controlled trials.