Publishing clinical trials

In this chapter we have looked at the results of published clinical trials of antidepressant medication. The published studies showed a significant, but surprisingly small, effect of antidepressants over placebos. But as I noted at the beginning of the chapter, those data represented only the beginning. As I later discovered, there were also studies that had been withheld from publication. These unpublished studies were clinical trials that did not show a significant benefit for drugs over placebo medication - trials that the drug companies withheld... 

The following example is taken from a published clinical trial. 

Atosiban is an antagonist of the oxytocin receptor that has been approved outside the USA as a treatment for preterm labor (tocolysis). Atosiban is a modified form of oxytocin that is administered by IV infusion for 2-48 hours. In a small number of published clinical trials, atosiban appears to be as effective as B-adrenoceptor-agonist tocolytics and to produce fewer adverse effects. In 1998, the FDA decided not to approve atosiban based on concerns about efficacy and safety. 

The first solution is the prospective promulgation of a set of criteria that every author must meet. Many journals publish their own specific guidelines or criteria, and these do not differ greatly in qualitative terms. In the practicality of publishing clinical trials, the following would be typical ... 

Pharmaceutical physicians in large pharmaceutical companies will only very rarely be exposed to the need for press releases concerning their clinical trials. In contrast, the small entrepreneurial pharmaceutical company may live or die on the outcome of a single clinical trial. The rapid dissemination of the results of such a clinical trial to the appropriate audience (shareholders and investment community) is legally required when material to the prospects of a small, public company. The press release then becomes an important tool for publishing clinical trial results. 

Clearly, other chapters in this book could have appeared in this section. An early chapter in this book is on informed consent its location is designed to indicate the supervening importance of that particular application of autonomy, beneficence and equipoise. Ethical behavior is also at the very centre of good clinical practices . The chapter on publishing clinical trials also examines some of the ethical aspects of that activity. Dr Belsey also enters into this area with his chapter on advertising and marketing . 

Chronic pain patients tend to have concurrent depression however, the antidepressants chosen may not have any pain-relieving properties. Antidepressants that affect one neurotransmitter in the brain, such as selective serotonin reuptake inhibitors have not appeared to be effective in the management of pain in clinical trials. Antidepressants that affect multiple neurotransmitters— namely, serotonin and norepinephrine—have been shown to be effective pain relievers.Two published metaanalyses have shown that tricyclic antidepressants amitriptyline, desipramine, imipramine, and nortriptyline are the most effective treatment for the management of neuropathic pain. ° These publications review the published clinical trial data for all agents available for the management of neuropathic pain. 

In the published clinical trials, several different BCG preparations were used, and the efficacy of these vaccinations ranged from negative 56% (some patients did worse with the vaccine) to positive 80%. Trials within the United States and Puerto Rico have shown efficacy rates of 6% to 29%. The primary benefit of BCG vaccination appears to be the prevention of severe forms of TB in children. Data from the BCG trials show that the incidence of tuberculous meningitis and miliary TB is 52% to 100% lower and that the incidence of pulmonary TB is 2% to 80% lower in vaccinated children younger than 15 years of age than it was in unvaccinated controls. 

This chapter has three objectives. First, it is necessary to discuss the ethics and desirability of publishing clinical trials, and the biases that may be involved with that process. Second, junior pharmaceutical physicians may benefit from some discussion of classic parts of an orthodox clinical trial report in a peer-reviewed journal, and some clues for effective oral presentations. Third, alternative forms of publication are discussed, including isolated abstracts and posters, electronic publication and press releases. The scope of this chapter is strictly formal publications regulatory documents (which are typically not published and are a different form of clinical trials reporting) and marketing materials are dealt with elsewhere. A summary and prospectus closes this chapter. 

ABSTRACT With the assumption of the validity of the Hardin Jones principle that the death rate of members of a homogeneous cohort of cancer patients is constant, three criteria for the validity of clinical trials of cancer treatments are formulated. These criteria are satisfied by most published clinical trials, but one trial was found to violate all three, rendering the validity of its reported results uncertain. 

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