In order to verify the effectiveness of a new drug for treating hypertension, clinicians used the drug for 100 patients with hypertension. Blood pressure did drop in 65 people. Therefore, the pharmaceutical factory claims that the drug is indeed effective. which of the following can weaken the above conclusions most? ['The blood pressure measurement time during medication is not fixed, and the blood pressure of patients with hypertension originally fluctuates during the day.', 'Take a pill that is consistent with the appearance of the drug, but contains no drug ingredients, for patients with hypertension, and the blood pressure of the patient does not drop.', 'Give the drug to a group of 100 patients with hypertension, and another group of 100 patients with hypertension who take the same shape but do not contain a drug component. The number of blood pressure drops in the former group is as large as in the latter group.', 'The doctor used the drug on 1,000 hypertensive patients, and only 500 of them had blood pressure drops.']