Design #1 is best because sources of systematic bias can be reduced as all patients undergo a similar approach to cancer therapy and monitoring, and all patients can be assessed by the same group of clinicians.

INCORRECT

The correct answer is (c).

Design #1 will allow careful prospective data collection, but has several major potential sources of bias. First, the study patients are those with breast cancer, but the comparison patients may have any type of neoplasm. If there are systematic disease-related differences in the experience of fatigue, or the response to the intervention, then some of the observed differences between study patients and comparators might be related to these rather than to the intervention itself. Second, the comparison group will be recruited in the same setting as the study patients. The same concerns about diffusion of the intervention by enthusiastic nurses that were raised when considering a controlled trial may occur during a survey, and could invalidate any comparative data. Third, patient recruitment is defined by a time period (four months) rather than a sample size. Although the investigators may have a good idea about the sample size that this period will yield, a lower-than-expected recruitment is still possible. This possibility, plus concern about the recruitment of a study group and a comparator group that vary substantially in size, suggests that an approach based on recruitment of a defined number of patients would be better. Finally, follow-up data will be collected at varying times depending on the chemotherapy. The design will result in a different number and timing of follow-up data points. Although these differences could be adjusted statistically and allow computation of a summary index, such as change in fatigue over time, they may introduce bias. For all of these reasons, the results obtained through Design #1 must be interpreted very cautiously.