Good Clinical Practice Journal

Below are the titles of articles published in the Good Clinical Practice Journal Volume 8 Issue 9 (September 2001).

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Note from the Editor
At recent meetings and in scientific publications, you will find that the subject of choice has involved the question of placebo. In this month's Comment, Dr Stephen DeCherney discusses equivalence trials following the revised Declaration of Helsinki.

Drs Benjamin Djulbegovic and Mike Clarke published an editorial entitled 'Scientific and ethical issues in equivalence trials' in the Journal of American Medical Association on 7 March 2001 following an article by Staszewski et al. on a randomised equivalence trial on antiretrovirals. Under the revised Declaration, it is unethical to conduct placebo-controlled trials in the case of AIDS/HIV. Equivalence trials are designed to prove that two treatments have the same effect. What makes this type of trial interesting is the way the data is interpreted. Drs Djulbegovic and Clarke discussed several aspects of equivalence trials, such as how to justify the use of a new intervention and how to choose the control group. As with other decisions we tale in life, we tend to compare drugs and separate them as superior and inferior. In the case of equivalence trials, you cannot do this. There is no space for superiority when the end result will show that there is no difference between a new drug and one on the market. How do investigators present such a trial to potential subjects? Patients must be encouraged to participate in trials. However, in equivalence trials, all those involved have to comply with the uncertainty principle that defines and sets a framework for enrolling patients in randomised-controlled trials.

This brings back the issue of choosing the comparator for an intervention. Who decides when to conduct superiority trials or equivalence trials? Usually, we refer to drug X, which was found to do better than drug Y or placebo in trial Z. What about drugs that have the same efficacy but in different situations? For example, patients differ through their medical history, race, sex and previous drug interactions. Does the comparator have a safety and efficacy profile that counteracts these differences? Another problem is faced by the statisticians. To interpret equivalence trials, you need more patients than in other types of trial to determine the effectiveness of the new drug. The results will show that either both drugs are effective for a specific indication or both are ineffective. There is still a lot to come on this one and more ink to dry in the debate over equivalence trials versus superiority trials.

Dr G Stephen DeCherney is Executive Vice President for Clinical Operations at PRA International in the USA. He is the author of more than 60 publications and has been the principal investigator on more than 100 research programmes.

Outsourcing pharmacovigilance � a CRO perspective
By Dr Ewan Millar
Abstract
Pharmacovigilance in the pharmaceutical industry has traditionally been an in-house company activity with dedicated units. Recently, however, there has been a trend to outsource pharmacovigilance to CROs who can offer a valuable resource with suitably qualified personnel.

Clinical trials in the elderly
By Prof. Peter Crome
Abstract
Survival into old age is increasing in both the developed and the developing world. What is more, older people are reaching later life in a generally healthier state. Unfortunately, older people are also more likely to develop adverse effects to medication and not just because they are taking more drugs.

The UK Ethics Review System � concerns and frustrations
By Dr Magnus Jaderberg
Abstract
The UK National Health Service introduced a sequential ethics review system in 1997 in response to many years of differences in the management and communication of Local Research Ethics Committees. The research community welcomed the idea of a Multi-Centre Research Ethics Committee pre-vetting studies of five or more sites, thereby reducing the work and time involved in local ethics review by LRECs.

Biotech medicines: at the confluence of innovation and clinical research (part II)
By Cecil Nick
Abstract
Biotechnology is having a major impact on expanding the boundaries of medicine, enabling the supply of therapeutic proteins as well as the manufacture of improved and novel proteins.