For approximately six months, a cardiologist has been prescribing a new statin to reduce serum lipids. A number of his patients have reported several side effects, including nausea and muscle pain, which in some cases have been severe. In a previous research study with another statin, the cardiologist asked patients to assess their level of muscle discomfort on a scale of 0 (no discomfort) to 10 (unbearable pain). Scores greater than 2 were suggestive of some damage and levels over 5 were associated with irreparable muscle loss. The cardiologist is concerned that some of his current patients appear to be at risk.

Accordingly, he contacts the drug company, who tell him that the side effects he is witnessing are common and harmless. In studies similar to his own, they have recorded an average (median) muscle discomfort score of 1. The cardiologist is not reassured and designs a double blind, randomised controlled study to answer the following research questions:

1. Do the levels of muscle discomfort reported by the patients taking the statin support the drug company's claim of an average of 1?
2. Does the statin lead to higher levels of muscle pain than the previous treatment (which acts as the control)?
3. Is muscle discomfort linked to the decrease in lipid levels?
4. Is there any evidence to link heart attack to treatment?

Twenty individuals are assigned randomly to either the statin or control group. The results are given in Table E1.

1.5 7 1.0 - Shapiro-Wilk statistic = 0.83 Expected Normal P = 0.003 0.0 0.5 -1.0 + Ch - Observed Value FIGURE A. NORMAL PLOT OF FOLLOW-UP MUSCLE DATA 1.5 7 1.0 - 0.5 - Expected Normal Shapiro-Wilk statistic = 0.87 10 - P = 0.01 0.5 - -1.0 + 0.0 0.5 1.0 1.5 2.0 2.5 Observed Value FIGURE B. NORMAL PLOT OF FOLLOW-UP MUSCLE DATA (SQUARE ROOT TRANSFORM).Diagnosis Six Month Review ID Gender Age Treatment Lipid Level Outcome (mg/dl) Muscle Score Lipid Level (mg/dl) Muscle Score 1 male 73 statin 260 0 184 3 no heart attack female 53 statin 251 0 148 0 no heart attack 3 male 75 statin 267 115 2 no heart attack 4 male 56 statin 259 0 124 4 heart attack 5 male 71 control 267 0 145 0 heart attack 6 male 97 control 254 0 129 1 heart attack female 40 control 266 0 150 1 heart attack male 76 control 251 0 118 0 no heart attack female 80 statin 273 0 113 5 no heart attack 10 female 76 statin 263 0 190 2 no heart attack male 64 control 261 0 115 heart attack 12 male 76 control 253 0 178 heart attack 13 female 83 statin 269 145 1 no heart attack 14 male 49 statin 253 0 149 5 no heart attack 15 male 57 statin 251 1 140 0 no heart attack 16 male 73 control 259 0 109 1 heart attack 17 male 71 statin 269 0 111 3 heart attack 18 male 58 control 265 0 170 0 no heart attack 19 male 74 control 268 0 169 5 heart attack 20 male 60 control 256 0 122 0 no heart attack TABLE E1. DATA ON THE COMPARISON OF THE EFFECTS OF STATIN 3 AND BETA-SITOSTEROL ON SERUM LIPIDS