The role of diet in promoting or preventing disease is a focus of nutritional epidemiology. In recent years, the field has embraced the idea that dietary patterns, as opposed to a single food or nutrient, are likely to have a bigger impact on health and disease prevention. The Mediterranean diet is characterized by the traditional food patterns of Mediterranean countries. The Mediterranean diet has consistently been shown to reduce the risk of all-cause mortality, cardiovascular disease mortality, and cancer mortality in several large prospective cohort studies.

Suppose that we work for the American Cancer Society, which would like to update its "Guidelines on Nutrition and Physical Activity for Cancer Prevention." Guidelines are based on current evidence, and their purpose is to provide recommendations for the general public.

We are tasked with critically evaluating one recent study that examined the association between Mediterranean diet and risk of ovarian cancer in the Nurses' Health Study, a prospective cohort study with 121,700 female nurses (Xie et al,Journal of Ovarian Research(2014) 7:112).

In this study, dietary information was measured prospectively every 2 to 4 years by a self-administered semi-quantitative, 131-item food frequency questionnaire. For each food, a portion size was given, and women were asked to choose from 9 intake frequencies from never to >=6 servings per day averaging over the prior year's intake. A Mediterranean Diet Score was calculated that considered consumption of certain fatty acids, legumes, cereals, fruits, nuts, vegetables, meat, dairy, and alcohol and ranged from 0 to 10.

The following excerpts are taken from the paper. Please address each associated question.

1. "The validity of our food frequency questionnaire was evaluated by comparison with food diaries in 192 women." Which type of bias are the study investigators trying to limit?

2. If the correlation between the food frequency questionnaire and food diaries is poor, is it more likely or less likely that this type of bias is present?

3. Ovarian cancers were identified either by self-reports or data from the National Death Index. Women or their next-of-kin were asked for permission to obtain and review pathology reports to confirm the diagnosis. Which type of bias are the study investigators trying to limit by confirming the ovarian cancer diagnosis?

4. "The follow-up rate was 97%." Which type of bias are the investigators trying to assess?

5.Based on the follow-up rate, is this type of bias likely?

6. Is the "Healthy Worker Effect" a concern in this study?

7. "Participants who left more than 70 items blank on the diet questionnaire were excluded from the analysis." Which types of bias were the study investigators trying to limit?

8. "All of this [dietary] information was collected prospectively..." What type of bias was avoided with prospective dietary data collection?

Hazard ratios for the association between Mediterranean Diet Score and ovarian cancer

9. Examine the results in the table above. Suppose that a Mediterranean diet truly reduces the risk of ovarian cancer. What sources of bias most likely accounted for the null or nearly null findings?