Medical Ethics

Session 3

Session 3

Harm-benefit assessment in the design and evaluation of clinical research protocols

A requirement for the ethical conduct of clinical research is a favorable balance between a research protocol's harms and benefits. In clinical research, participants may or may not derive direct health-related benefits. The primary goal of research is the acquisition of scientific knowledge.

Clinical research typically comprises therapeutic and non-therapeutic research components. An assessment of a particular protocol's harm-benefit balance should take this into account : potential harms associated with therapeutic components may be justified by the prospect of direct medical benefits; potential harms associated with non-therapeutic components must be justified by the prospect of acquiring valuable knowledge.

Objectives :

  1. To explore a component-based systematic analysis of proposed research protocols.
  2. To understand how the harms associated with therapeutic and non-therapeutic research components should be evaluated and justified separately.
  3. To understand the concept of minimal risk in the Common Rule.
  4. To understand how to evaluate proposed harms and benefits in clinical research involving children, to which separate requirements are applied in Subpart D of the Common Rule.
  5. To understand the potential applicability of the component-based approach to other vulnerable populations, such as individuals with impaired decisional capacity.


Required reading for this session

Cases for discussion

Case 1

A researcher proposes to study population differences in insulin sensitivity, resting energy expenditure and body composition in overweight children and non-obese children of overweight parents. He proposes periodic testing and evaluation at five year intervals until the children reach adulthood. Pertinent research procedures and interventions include: acquisition of a medical history and standardized psychological testing; fasting blood tests for a variety of biochemical markers; bone-age X-ray; DEXA scanning for bone density meaurement; oral glucose tolerance test; 24-hour urine collection; measurement of basal metabolic rate by indirect calorimetry; a two-day/one-night admission to a clinical ward for performance of hypergylcemic and hyperinsulinemic challenges that involve placement of IV lines and measurement of serum glucose, free fatty acids and insulin levels; and an MRI of the abdomen to evaluate visceral fat distribution.

Case 2

This research proposes to administer to preterm and full-term newborns simultaneous 24-hour infusions of palmitate and acetate labeled with the stable (non-radioactive) isotope carbon-13, then measure the incorporation of each into surfactant, collected by tracheal aspiration. Subjects of the study would include approximately 10 full-term intubated infants with normal lungs and 15-20 preterm (24 to 28 weeks gestational age) intubated infants with respiratory distress syndrome. The overall goal of the proposed study is to better understand the potential differences in precursor preferences in surfactant synthesis between preterm infants with immature lungs (requiring mechanical ventilation) and term infants with normal lung function. The three specific aims of the study are to: (i) determine the rate of surfactant using synthesis de novo synthesizing fatty acids (acetate); (ii) determine the rate of surfactant synthesis using preformed fatty acids (palmitate); and (iii) compare the rates of incorporation in preterm infants versus term infants with normal lungs.

Relevant section of the Grant Application

 

Questions

For each case:

Is the research characterized by minimal risk, a minor increase over minimal risk, or greater than a minor increase over minimal risk?

What other considerations are pertinent in determining whether the research is approvable by a local IRB?

Would you vote to approve or disapprove the research proposal as submitted, and why?

 

Additional resources