Rethinking Clinical Research: Methodology and Ethics

Ethical and social implications of clinical research

The main objectives of this project are to address each of the problems defined above and crosscutting themes. One investigator is designated as the lead for each objective, with a plan for all investigators will contribute to the products defined for each objective (see Timeline):

1. The Efficacy-Effectiveness Problem. A classic paper by Sir Archie Cochrane and Sir Austin Bradford Hill argued that the value of treatments must consider three questions: 1) Can it work? 2)  Does it work? And 3) Is it worth it?  These distinct questions must each be evaluated using a different unique methodology. The first and second Cochrane/Bradford Hill questions relate to the efficacy-effectiveness problem. One objective is to articulate a clearer differentiation of efficacy and effectiveness research.  In general, efficacy studies focus on the evaluation of interventions under ideal circumstances (the “Can it work?” question). Effectiveness studies consider the effect of treatment under real-world conditions (the “Does it work?” question). However, our previous work showed that these tenets are inconsistently used in research, which has negative effects on understanding and applying the research literature in practice.  Based on detailed reviews of the literature, we will formulate and propose a standard definition for effectiveness studies that will be representative of routine practice and real-world conditions. (Lead investigator: Porzsolt)

2. The Surrogate Marker Problem. The third Cochrane/Bradford Hill question relates to the surrogate marker problem (the “Is it worth it?” question). We will review methods for assessing patient reported outcomes, and review methodologies for economic evaluation. (Lead investigator: Kaplan)

3. The Transparency Problem.
One paper will address these problems as applied to depression treatment studies. By federal law, depression treatment studies conducted in the US should be registered on ClinicalTrials.gov and report their results in a timely and honest fashion (without hidden, spun, or selectively reported results). Previous reviews have found low rates of reporting compliance, which might create bias by hiding results that are not supportive of a favored treatment. We are unaware of a previous review focused on depression. (Lead investigator: Schmaling)

Theme paper 1. Based on the results of objectives I-3, we will write a manuscript focused on relevant policy implications, including a comparison of international clinical practice guidelines for the treatment of common conditions.  Each member will contribute a section relevant to their interests.  Dr. Schmaling will oversee a section on depression, Kaplan will oversee a section on high blood pressure control, and Porzsolt will lead the section on cancer prevention and control.  The goal of the paper is to inform future iterations of treatment guidelines relevant to these three clinical problems.

Theme paper 2. A second thematic paper will examine the ethical issues in and social implications of clinical research, such as the reliance on randomized clinical trials (RCTs), as informed by professional codes of ethics and the Belmont Report. The use of RCTs may be seen as inconsistent with ethical principles such as fidelity, responsibility, and justice. Ethics reviews of clinical research (i.e., the work of institutional review boards) are focused on the initial phases of a research project, such as how subjects are identified, and informed consent for the research procedures. However, there is little consideration of the latter phases of research, such as ethically-informed data analysis and dissemination. (Lead investigator: Schmaling.)