Source: NEJM -

GENERAL QUESTION: Is an event X a plausible cause of the event Y?

ONE WAY TO ANSWER: Show that event Y occured before event X in as many cases as possible.

TECHNIQUE: Temporally reorder the history of every case relative to the date of occurence of X

SPECIFIC QUESTION: If Kaposi's sarcoma-associated herpesvirus (KSHV) (event X) is the cause of Kaposi's sarcoma (event Y), serologic evidence of infection should be present in patients before the disease develops.

PAPER CONCLUSIONS: In most patients with Kaposi's sarcoma and AIDS, seroconversion to positivity for antibodies against KSHV-related nuclear antigens occurs before the clinical appearance of Kaposi's sarcoma . This supports the hypothesis that Kaposi's sarcoma results from infection with KSHV. (N Engl J Med 1996;335:233-41.)