There are various aspects to take into consideration when constructing an RCT and many of the issues involved will be discussed in lectures, through practical and discussion groups: design options, issues in good clinical practice such as informed consent, blinding, process evaluation, power calculation and randomization, missing values and data-analyses in general. 

As there are many potential errors associated with health services research, this module will focus on various key features of RCT design, with particular emphasis on design, validity and data-analysis.

A well-designed, methodologically sound RCT evaluating an intervention can provide strong evidence of a cause-effect relation if one exists. These studies are often used to chance practice and taken up in guidelines, being the ultimate goal of research on therapeutic effectiveness. On the other hand, poorly designed studies are dangerous because of their potential to influence practice based on flawed methodology.

The umbrella term ‘intervention study’ refers to those study designs in which one or more independent variables are manipulated by the investigator, whereas the other independent variables are kept constant or controlled at the same time. This ‘experimental’ approach is regarded the most powerful study design for discovering causal relationships and can be the sturdiest ways of doing research, however, has many ethical and design issues to be taken into account. This module will focus on experimental research in human beings outside the laboratory. ‘Clinical trial’ is a common name to indicate this type of experiments especially as it is often used to assess the efficacy and effectiveness of a new treatment for patients.

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Knowledge and understanding

Ability to distinguish between various classes of intervention studies (e.g. pre-experimental, quasi-experimental and true experimental designs; parallel group designs, cross-over designs, N-of-1 design, non-inferiority trials etc.).   

 1.

Knowledge of and insight into the rationale of and prerequisites for experimental intervention research.    

2.

Knowledge of the historical development of intervention trials.    

3.

Ability to identify the core elements of the ‘classic’ intervention study design (RCT = parallel, placebo-controlled, double-blind, randomized trial): choice of study subjects (in- and exclusion criteria, study size), choice of outcome measures and follow-up time (PICOT). Ability to choose intervention strategies and contrasts, informed consent procedure, randomization, prestratification, blinding, dealing with protocol deviations (drop-outs, non-compliance, missing values), registration of (serious) adverse events.   

 4.

Ability to distinguish between various alternative intervention study designs (e.g., cross-over design, factorial design, Latin square design, prerandomization design (Zelen design), sequential analysis approaches, N of 1 trial designs, group-randomized trial design).  

 5.

Ability to distinguish between alternative methods of random allocation of trial participants: adaptive vs. fixed allocation randomization procedures (e.g., simple randomization, stratified randomization, block randomization, response randomization, replacement randomization, biased coin method, minimization, balancing, unequal randomization).   

 6.

Knowledge of and insight into relevant aspects of the design/choice of the study population (e.g., inclusion and exclusion criteria, eligibility considerations, source for selection, recruitment procedures, patient registration).  

 7.

Knowledge of and insight into relevant aspects of the design/choice of the intervention (e.g., treatment schedule (route of administration, dosage, duration), intervention contrast (placebo, usual care), dealing with co-interventions).  

 8.

Knowledge of and insight into relevant aspects of the design/choice of outcome measurement (e.g., primary vs. secondary outcome measures, timing of measurements, quality aspects (validity, reliability, sensitivity-to-change / responsiveness), intended vs. unintended effects).  

 9.

Ability to identify pros and cons of a run-in period (qualification period). 

10.

Knowledge of and insight into the role of placebo intervention within the context of a randomized trial. 

11.

  Knowledge and insight into the characteristics and differences between pragmatic and explanatory designs regarding designing, performing and interpreting the results of such trials  

12.

Knowledge and understanding of the so-called mixed methods designs. Designs were a combination of quantitative and qualitative research methods are used  

13.

Knowledge, understanding and skills regarding procedures that deal with protocol violations. 

14.

Knowledge of and insight into strategies and procedures of statistical analysis of intervention trial results (e.g., intention-to-treat vs. per-protocol (valid cases) analysis, appropriate statistical techniques). 

15.

Knowledge, understanding and skills regarding procedures for sample size and power calculation in intervention trials and more in general. 

16.

Ability to interpret the results of an intervention trial and to draw balanced conclusions with respect to the effectiveness of an intervention. 

17.

Knowledge of and insight into the requirements for intervention trial protocols and reports. 

18.

Knowledge of and insight into planning, organizational, administrative and other practical aspects of intervention trials (e.g., documentation, design of forms, standard operating procedures (SOPs), data management, audits, multicentre trials). 

19.

Knowledge of and insight into the ethical and legislative aspects of intervention trials (e.g., METC-procedures, WMO, GCP, international harmonization, requirements).