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Biomedical subjects

J F Lekkerkerker

Publications and source records attributed to J F Lekkerkerker.

At least 19 recordsLinked to original sources
PubMed2002

The use of placebo-controlled and non-inferiority trials for the evaluation of new drugs in the treatment of postmenopausal osteoporosis.

Registration of new agents for the treatment of postmenopausal osteoporosis has been based over the past few years on placebo-controlled phase III trials with the incidence of patients with new vertebral/nonvertebral fractures as the most usual primary endpoint. The use of a placebo in diseases where an active treatment is available has been a matter of debate following the update of the Declaration of Helsinki by the World Medical Association which questioned this trial design. Current regulatory recommendations within the European Union suggest that placebo-controlled trials are still the best option when assessing the efficacy and safety of new drugs intended for the treatment of postmenopausal osteoporosis. This suggestion seems to be in apparent contradiction with the current content of the Declaration of Helsinki. This paper addresses the ethics and feasibility of placebo-controlled trials in the treatment of postmenopausal osteoporosis, in the light of available therapeutic options, and discusses possible alternative approaches in those patients where placebo treatment could be deemed to be unethical. It is concluded that placebo-controlled trials remain the most efficient design to establish the efficacy and safety of a new agent for the treatment of postmenopausal osteoporosis. Such trials are feasible and ethically acceptable in patients with osteoporosis but without prevalent vertebral fractures. Conversely, in patients with prevalent vertebral fractures, placebo-controlled trials are ethically questionable and non-inferiority trials are more appropriate. A relative margin of non-inferiority of 20-30% is suggested, to be discussed on a case by case basis.

Aged↗
PubMed2001

[Risk of convulsions due to the use of bupropion as an aid for smoking cessation].

Bupropion is a new aid in smoking cessation. Since marketing of this product in the Netherlands (from December 1999 on), 7 cases of (possible) convulsions have been reported. In 3 cases there was a contraindication in the form of a history of epilepsy. The four other cases concerned tonic-clonic epileptic seizures in patients with no history of epilepsy and no combination with other medication. In view of the seriousness of this, already known, side effect of bupropion, physicians ought to be sensitive to situations with increased risk of this side effect. In addition it is advised to explain to the patient the proper use of bupropion, which is not comparable to nicotine chewing gum and should be swallowed whole due to the slow release properties of the tablet.

Adverse Drug Reaction Reporting Systems↗
PubMed2000

[Drug interactions of Hypericum perforatum (St. John's wort) are potentially hazardous].

Hypericum can lower the plasma levels of simultaneously administered drugs by induction of metabolism. Combinations of hypericum products with warfarin, cyclosporin, oral contraceptives, theophylline, fenprocoumon, digoxin and indinavir have led to reported interactions and reduced therapeutic activity. It is therefore not advisable to combine hypericum products with other drugs, especially CYP3A4 and p-glycoprotein substrates. Discontinuing hypericum after protracted use may lead to higher plasma levels of the drugs used simultaneously, with the risk of adverse effects. Registered homeopathic preparations with a dilution of 1 in 10,000 or weaker may be regarded as safe.

Anticoagulants↗
PubMed2000

[Clinical evaluation of efficacy and adverse effects in the (European) registration of drugs: what does it mean for the doctor and patient?].

The clinical criteria for admission of new drugs to the European common market have become more stringent in recent years. Increasingly often, the manufacturer is required to demonstrate that the new drug offers a clinically visible and relevant benefit to the patient. Efficacy and adverse effects should not only be studied by comparative trials with placebo, the registration authorities also expect the drug to be compared with the standard treatment already available. Such trials should prove that the balance between efficacy and adverse effects of the drug is better than that of placebo and at least as good as the standard treatment, as regards not only statistical significance but also clinical relevance. Therefore, Dutch and European assessment reports and product information may be increasingly useful to prescribers, patients and insurers in determining the role and therapeutic value of new drugs within the existing therapeutic possibilities concerning certain diseases.

Clinical Trials as Topic↗
PubMed2000

The low dose (1 microg) ACTH stimulation test for assessment of the hypothalamo-pituitary-adrenal axis.

Traditional testing of the hypothalamo-pituitary-adrenal axis function has relied essentially upon the insulin tolerance test or the metyrapone challenge: both tests are not only uncomfortable, but carry also real dangers. The standard ACTH stimulation test uses an extremely hyperphysiological amount (250 microg) of ACTH to evaluate a physiologic response, which may result in false normal responses. The proposed low dose (1 microg) ACTH test is more physiological and more sensitive, especially in cases of mild adrenal insufficiency and allows also to assess pituitary-adrenal suppression after long-term treatment with glucocorticoids. According to the rules of evidence-based medicine, the low dose ACTH test should replace the conventional 250 microg test when evaluating for central adrenal insufficiency.

Adrenal Insufficiency↗
PubMed1999

[Role of cytochrome P450 enzymes in pharmaceutical preparations].

Cytochrome P450 enzymes are responsible for pharmacokinetic interactions with sometimes serious adverse effects. If a drug is known to be a substrate, inhibitor or inducer of one of the cytochrome P450 isoenzymes, it can be estimated with which other drugs it will interact. The interaction profile of a new drug plays an increasing role in the assessment of the benefit/risk ratio by regulatory authorities. Interactions in practical situation can, however, never be ruled out without proper precautions of both pharmacists and physicians. More attention for the possible occurrence of interactions and searching for a good alternative for one of the drugs to be used should lead to a reduction in the number of adverse events related to interactions.

Cytochrome P-450 Enzyme Inhibitors↗
PubMed1998

[More openness about the registration of drugs in the Netherlands. College for the Review of Medicinal Products].

The applications submitted to the Drugs Evaluation Board contain information that is important for correct use of the drug in question in clinical practice. Not all this information is given in the published literature, certainly not at the time of registration. Recently, legal provisions on publication of data in connection with a registration were clarified. The Board no longer sees any objection to introduction of a national, public assessment report explaining the arguments involved. The quality of evaluation of pharmaceutical products, also in connection with the reimbursement system, cannot but improve if a justification of the evaluation is published.

Drug and Narcotic Control↗