Good clinical practice (GCP). / Dansk historie og engagement i international udvikling.

The wave of Good Clinical Practice (GCP) that swept Europe in the mid-eighties also hit Denmark. The influence from the USA was highly significant. However, the history of GCP in Denmark builds upon the ethical and scientific requirements for clinical trials of drugs which had developed over the preceding two decades. Furthermore, quality assurance of trials were already in progress. The Danish health authorities and the pharmaceutical industry were cooperating well in the evolution of GCP in Denmark. Parallelly, Denmark took an active part in the international harmonisation of the various GCP-guidelines within the Nordic countries, in the European Community, and world-wide through the development of the WHO- and the ICH-guidelines. In the work with these guidelines, several experts from a number of countries collaborated with Danish experts. Through this continuous interaction, Denmark profited from the tight connection with the circles and institutions where this development took place, both causing an increased awareness of GCP in Denmark, and an indisputable contribution from Danish participants to the international GCP-development. In 1987, an interdisciplinary Danish GCP Society was established. This has increased the understanding of GCP and, together with other activities, promoted the cooperation between the health authorities, the law-based ethics committee system, the sponsors, the investigators, and the Danish Data Protection Agency. The Society has arranged numerous courses and seminars, and held conferences and meetings in order to inform about GCP. The Danish GCP Society seems internationally to be rather unique in its scope and work. It is concluded that Denmark is well prepared for the coming regulations of trials on medicinal products proposed by the EU.

Absence of interaction between tiagabine, a new antiepileptic drug, and the benzodiazepine triazolam.

In a randomised, double blind, placebo-controlled, four-period cross-over study in 12 healthy volunteers, the potential pharmacodynamic and pharmacokinetic interactions between the new antiepileptic drug, tiagabine, and the benzodiazepine, triazolam, were investigated. A single dose of tiagabine HCl 10 mg did not enhance the sedative or cognitive effects of a single dose of the benzodiazepine triazolam 0.125 mg, although the time-course of the effects was prolonged. Furthermore, tiagabine did not produce any statistically significant effects on the pharmacokinetics of triazolam. Similarly, the pharmacokinetics of tiagabine were not modified by triazolam. Tiagabine was well tolerated when administered alone or with triazolam.

Early- and late-onset pelvic inflammatory disease among women with cervical Chlamydia trachomatis infection at the time of induced abortion--a follow-up study.

After termination of a double-blind, randomized study on erythromycin in the prevention of post-abortion infection, 34 women (14 treated with erythromycin, 20 not treated with erythromycin) harbouring Chlamydia trachomatis were followed up within 6 weeks and again 2 to 24 months after the abortion in order to detect an early- and late-onset pelvic inflammatory disease (PID). For statistical analysis survival analysis by Kaplan-Meir estimates and Mantel-Cox test were carried out. Untreated women with C. trachomatis infection at the time of abortion had a cumulative risk of 72% of developing early and/or late PID, if observed for 24 months. This cumulative risk was significantly reduced to 8% if the C. trachomatis infection was treated at the time of the abortion. Screening for and treatment of C. trachomatis is warranted, especially in women < or = 25 years old, to avoid early and late-onset PID after induced first trimester abortion.

A double-blind randomized study of the effect of erythromycin in preventing pelvic inflammatory disease after first trimester abortion.

OBJECTIVE: To assess the prophylactic use of erythromycin in prevention of post-abortal pelvic inflammation disease (PID) in first trimester abortion. DESIGN: Double-blind, randomized controlled trial. SETTING: Department of Surgery, County Hospital, Denmark. SUBJECTS: Four hundred and thirty two women who were to undergo induced abortion before 12 weeks gestation were randomized to be treated either with prophylactic erythromycin or a placebo. INTERVENTION: The women were randomized to receive a placebo or erythromycin, 500 mg twice a day for 7 1/2 days starting the evening before the abortion. All the women were investigated for Chlamydia trachomatis and Neisseria gonorrhoea before the abortion. MAIN OUTCOME MEASURES: Frequency of cervical C. trachomatis and N. gonorrhoea and frequency of PID after abortion. RESULTS: Fifty four women were excluded after randomization. The frequency of PID was 11% (20/189) in the erythromycin group and 16% (30/189) in the placebo group (P = 0.13, chi 2-test). The prevalence of C. trachomatis was 19% (15/78) in women less than or equal to 20 years of age, 13% (14/109) in women between 21 and 25 years and 2% (5/241) in women greater than or equal to 26 years of age. In women positive for C. trachomatis erythromycin prophylaxis significantly reduced the frequency of PID to 8% (1/13) compared with 43% (6/14) in the placebo group (P = 0.051, logistic regression analysis). Erythromycin had no effect on other potential high risk groups (first pregnancy, nulliparous, less than 20 years of age, and women with previous PID). CONCLUSION: Prophylactic erythromycin is not warranted for all women having an abortion. Cervical C. trachomatis is a risk factor for postabortal PID, and prophylaxis with erythromycin significantly reduces the frequency of PID. However, only a few women with PID had cervical C. trachomatis, and the prevention of post-abortal PID remains a major challenge requiring further studies.

[Good clinical practice. Requirements for clinical documentation on the introduction of new drugs]. / Good clinical practice. Krav til klinisk dokumentation ved introduktion af nye laegemidler.

Good clinical practice (GCP) includes protection of the involved patients/volunteers and quality of the clinical documentation which forms the basis for registration of a preparation. During recent years, guidelines for GCP have been presented from various quarters. These describe the requirements which must be fulfilled to document the effect and safety of a new preparation. The requirements comprise involvement of the investigator and also of the monitor and sponsor and ethical committees. In this article, the contents of the guidelines are reviewed and the significance these obtain of the involved parts in the clinical development of medicinal preparations.