Placebos run-ins

Fortunately, there is a methodological feature of these clinical trials that makes the charge of falsifying the initial data somewhat less problematic than it might otherwise be - as long as those are the only data that were fudged. All of the trials we analysed had what is called a placebo run-in or wash-out phase. The way this works is as follows. After people are assessed for inclusion in the trial, they are all given a placebo for a week or two. After this run-in period, the patients are reassessed, and anyone who has improved is excluded from the trial. The baseline severity scores that we used in our analyses were those taken after the placebo... 

One of the main reasons for excluding patients from clinical trials is to make it easier to find differences between the drug and the placebo.26 There are two ways in which excluding some patients from the trials can help accomplish this aim. One is to eliminate those who are most likely to respond to a placebo. To accomplish this goal, patients are excluded from clinical trials if they have only been depressed for a short time, if they are only mildly depressed or if they respond to placebo treatment during the placebo run-in phase. 

Leber, Paul, Approvable Action on Forrest Laboratories, Inc. Nda 20-822 Celexa (Citalopram Hbr) for the Management of Depression , in Memorandum to the Department of Health and Human Services, Public Health Service, Pood and Drug Administration, Center for Drug Evaluation and Research, Washington, DC, 4 May 1998 Lee, Sandra, John R. Walker, Laura Jakul and Kathryn Sexton, Does Elimination of Placebo Responders in a Placebo Run-in Increase the... 

Quitkin, Frederic M., Patrick J. McGrath, Jonathan W. Stewart, Katja Ocepek-Welikson, Bonnie P. Taylor, Edward Nunes, Deborah Delivannides, Vito Agosti, Steven J. Donovan, Donald Ross, Eva Petkova and Donald F. Klein, Placebo Run-in Period in Studies of Depressive Disorders Clinical, Heuristic and Research Implications , British Journal of Psychiatry 173 (1998) 242-48... 

A larger randomized double-blind placebo-controlled trial [5] of 59 migraine sufferers (who had not taken feverfew before) found that feverfew treatment was associated with a reduction in the mean number and severity of attacks and the degree of vomiting, but the duration of each individual attack was unaltered. The study period was 9 months in total consisting of 1 month placebo run-in followed by 2 x 2 months of either feverfew ( 82 mg/day) or placebo after which patients were switched to the other leg of... 

The use of buspirone in social phobia has also been investigated by Schneier et al. [1993]. In this 12-week open trial, 21 patients who met DSM-III-R criteria for social phobia and did not display a response during a 1 -week placebo run-in, went on to receive buspirone. The drug was initiated at 5 mg three times a day and was increased by 5 mg/day every 3 days to a maximum dosage of 60 mg/day or until side effects prevented further dose increases. Seventeen patients completed the trial. At the end of week 12, 8 [47%] of the 17 subjects were rated as much to very much improved on the Clinical Global Impression Scale (Guy 1976]. Of those subjects tolerating doses of 45 mg/day or more, 67% [9/12] were at least much improved. ... 

In a 9-week, single-blind, placebo-controlled pilot study in 72 patients with multiple sclerosis who took modafinil 200 mg/day for 2 weeks, there was significant improvement in fatigue compared with placebo run-in treatment (8). The most frequent adverse effects were headache, nausea, and anxiety, and these were rated as either mild or moderate. 

Flunitrazepam in a 2-mg dose was compared with zolpidem in a 20-mg dose. Forty-two insomniac female in-patients between 30 and 65 years of age were included in a doubleblind, parallel group trial and were randomly allocated to the two treatments. Study duration was 9 days with 2 days of placebo run-in, 5 days of active medication, and 2 days of placebo withdrawal. Sleep latency, sleep dura-... 

Many trials are planned with a placebo run-in, that is to say a period before the trial proper starts and during which all patients receive placebo. There seem to he two common reasons. First, the run-in period may permit the trialist to operate some screening procedure, in particular as regards compliance with a treatment regime, which may help to decide which patients will enter the trial proper. Second, it is argued that a run-in period is necessary to permit a clean comparison of the treatments in the trial. 

Senn SJ (1997) Are placebo run ins justified. British Medical Journal 314 1191-1193. 

In a single-blind, placebo-run-in, dose-escalation study in 36 patients with complex... 

In a single-blind, placebo-run-in, dose-escalation study in 36 patients with complex regional pain syndrome, followed for 12 months, there were substantial improvements in patient and assessor-rated dystonia scores, pain, disability, and quality-of-life [36 ]. There were 89 adverse events in 26 patients they were related to baclofen (n = 19) or pump/catheter system defects ( = 52) or could not be specified (n = 18). 

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