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T R Weihrauch

Publications and source records attributed to T R Weihrauch.

At least 19 recordsLinked to original sources
PubMed2004

[Clinical research with pharmaceutical agents in Germany: effects of the 12th amendment to the German Drug Law].

The European Clinical Trials Directive came into force on April 4th, 2001. This regulation will be implemented into the German Drug Law (AMG) through the 12th amendment to the AMG. It will impose major changes on the preparation and conduct of clinical studies with medicaments. In particular, the procedure to gain an ethical committee's approval and permission for multicentric studies from the German Federal Authority (BfArM) will increase bureaucracy and complexity for the sponsor. The new German procedures, which by far exceed the European regulation, will lead to increased costs and will require more time for the preparation of clinical studies.

Clinical Trials as Topic↗
PubMed2000

[Career opportunities for female and male physicians in the pharmaceutical industry].

INTRODUCTION: Pharmaceutical medicine is not only a mainstay in clinical drug development and marketing of drugs in pharmaceutical industry but also a challenging alternative to the clinic and outpatient practice for physicians. Since most of them have only a vague notion of what a career in this sector of industry involves, this paper attempts to display the scope of opportunities and responsibilities for physicians and to answer some of the most frequently asked questions. JOB PROFILES: Areas for physicians are preclinical research, clinical research, drug safety, biometry, scientific relations, marketing and sales departments, working as company physician, training of sales representatives, health policy and project management. Earnings, continued and postgraduate training, job changing as well as possibilities of information on a career in the pharmaceutical industry are described. CONCLUSION: Despite the wide range of job profiles, a physician is still a physician in the pharmaceutical industry: his or her aim is to help patients and relieve their suffering through ethical and innovative therapeutic research. This aim is achieved through committed involvement in the development and marketing of new, effective and safe drugs.

Career Choice↗
PubMed2000

[Placebo effects and adverse effects in clinical trials].

BACKGROUND: It is well known that placebos evoke a variety of effects in the human body. It is less known that placebo medication can produce adverse drug reactions (ADRs). METHOD: The efficacy and, as the main topic, the tolerability were investigated from an international clinical data pool on placebo-controlled randomized multicenter studies of 5 different groups of indications. The therapeutic areas analyzed were neuropsychiatry (nimodipine, ipsapirone), cardiology (nisoldipine), metabolism (acarbose) and gastroenterology (hydrotalcit). RESULTS: The placebo efficacy was evident and varied not only in comparison to 5 indication groups analyzed, but also within them. Placebo showed for example hardly an effect on the symptomatology of stroke patients with a severe neurological deficit in comparison to verum while there was a 50% improvement in symptoms following placebo application in patients with a mild stroke. In angina patients exercise tolerance increased under placebo by 10% (time to onset of ST segment depression and symptoms of angina) while verum showed a 22% improvement. In diabetes placebo had no effect as compared to baseline and to a verum on blood glucose and HbA1C. ADRs could be observed under placebo treatment. The frequency and kind of placebo-induced ADRs varied also between the indication groups, i.e. typical CV side-effects were observed in CV controls. The placebo ADR profile was similar to the reference drug also. Some ADRs were reported even more frequently under placebo than under verum, like "dry mouth" in patients with general anxiety status. CONCLUSIONS: Placebo therapy is frequently effective and is not a "non-therapy". Placebo effects can be shown only by direct comparison with a "non-therapy". A placebo therapy is frequently accompanied by adverse drug reactions (ADRs) just as a verum therapy. Placebo ADRs are frequently illness- and verum-specific. Effects and ADRs of placebo therapy must be known, to judge the effect of verum medication in controlled clinical trials. The mechanisms of placebo effects are manifold (e.g. endorphine release, conditioned learning). Since placebo therapy outside of evidence-based medicine (use of drugs without proven efficacy = pseudoplacebos) may potentially also cause serious side effects, the use may not only be useless but also harmful.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

[Placebo effect in clinical trials].

BACKGROUND: It is well known that placebos evoke a variety of effects in the human body. It is less known that placebo medication can produce adverse drug reactions (ADRs). METHOD: The efficacy and, as the main topic, the tolerability were investigated from an international clinical data pool on placebo-controlled randomized multicenter studies of 5 different groups of indications. The therapeutic areas analyzed were neuropsychiatry (nimodipine, ipsapirone), cardiology (nisoldipine), metabolism (acarbose) and gastroenterology (hydrotalcit). RESULTS: The placebo efficacy was evident and varied not only in comparison to 5 indication groups analyzed, but also within them. Placebo showed for example hardly an effect on the symptomatology of stroke patients with a severe neurological deficit in comparison to verum while there was a 50% improvement in symptoms following placebo application in patients with a mild stroke. In angina patients exercise tolerance increased under placebo by 10% (time to onset of ST segment depression and symptoms of angina) while verum showed a 22% improvement. In diabetes placebo had no effect as compared to baseline and to a verum on blood glucose and HbA1C. ADRs could be observed under placebo treatment. The frequency and kind of placebo-induced ADRs varied also between the indication groups, i.e. typical CV side-effects were observed in CV controls. The placebo ADR profile was similar to the reference drug also. Some ADRs were reported even more frequently under placebo than under verum, like "dry mouth" in patients with general anxiety status. CONCLUSIONS: Placebo therapy is frequently effective and is not a "non-therapy". Placebo effects can be shown only by direct comparison with a "non-therapy". A placebo therapy is frequently accompanied by adverse drug reactions (ADRs) just as a verum therapy. Placebo ADRs are frequently illness- and verum-specific. Effects and ADRs of placebo therapy must be known, to judge the effect of verum medication in controlled clinical trials. The mechanisms of placebo effects are manifold (e.g. endorphine release, conditioned learning). Since placebo therapy outside of evidence-based medicine (use of drugs without proven efficacy = pseudoplacebos) may potentially also cause serious side effects, the use may not only be useless but also harmful.

Clinical Trials as Topic↗
PubMed1999

Placebo--efficacy and adverse effects in controlled clinical trials.

UNLABELLED: The therapeutic efficacy of placebo in a series of diseases has long been known. It is less well known, however, that treatment with placebo can also produce significant adverse drug reactions. Therefore, the placebo drug reactions from controlled trials were studied for the first time systematically. METHOD: The efficacy and the safety of placebos were investigated using patient and drug data pooled from randomized, placebo-controlled, multicentre studies in five different groups of indications covering the therapeutic areas of cardiology (nisoldipine), neurology/psychiatry (nimodipine/ipsapirone), metabolism (acarbose) and gastroenterology (hydrotalcite). RESULTS: The efficacy of placebo was clear, and varied not only between the five indication groups but also within them. Whereas placebo, unlike active treatment, produced hardly any improvement in symptoms in patients with severe stroke, it was as effective as active treatment in patients with mild neurological deficits, producing an improvement of about 50%. In patients with angina pectoris, placebo produced an increase in exercise tolerance (treadmill walking time to onset of ST-segment depression and angina attacks) of about 10% on average, compared with about 22% under active treatment (nisoldipine). In diabetes therapy, placebo produced no improvement in fasting and postprandial blood glucose levels compared with active treatment (acarbose), and also had no effect on HbA1C values. ADVERSE EFFECTS OF PLACEBO: Adverse drug reactions were observed under treatment with placebo. The frequency and type of placebo-induced adverse reactions also varied between indication groups. For example, typical cardiovascular effects such as tachycardia were observed in the control group. The placebo side effect profile was largely similar to the side effect profile of the active treatment. Some adverse drug reactions (such as "dry mouth" in patients with generalized anxiety syndromes) were observed more frequently under placebo than under active treatment. CONCLUSIONS: Treatment with placebo is frequently effective and cannot therefore be considered as "non-treatment". Placebo effects can only be quantified by direct comparison with "non-treatment". Like active treatment, treatment with placebo is frequently accompanied by adverse drug reactions. Placebo adverse effects are often disease- and active treatment-specific. The effects and adverse effects of a placebo need to be known before the effects of active treatment in controlled clinical trials can be assessed. The mechanisms of placebo effects are many and varied (e.g. endorphin release, conditioning). Since the use of drugs without regard to evidence-based medicine (prescription of drugs without proven efficacy = pseudoplacebos) may clearly also result in serious adverse effects, such practice may not only be non-beneficial but may even be harmful.

Controlled Clinical Trials as Topic↗
PubMed1998

[Drug research in Germany--problems and chances--from the viewpoint of the drug industry].

A trend can be observed for multinational research-based drug companies shifting their resources away from Germany (and partly also from Europe) and expanding their preclinical and clinical drug research and development programmes and organizations in the USA. The main reasons, which are presently under discussion in Germany, are the image and public acceptance of clinical drug research, professionalism of clinical studies (i.e. availability of an adequate infrastructure), the process of ethics committees votes, the citation impact of publications, the legal obstacles, the implementation of Good Clinical Practice (GCP), the regulatory and institutional situation and the political environment. These problems have been recognised and appraised recently by the pharmaceutical industry, universities, scientific associations, and governmental institutions. Prerequisites to improve the basic conditions of clinical research in Germany to make it internationally competitive are proposed in this paper.

Clinical Trials as Topic↗
PubMed1997

[Multi-national clinical therapy studies. Design, management and costs].

The development of new drugs requires increasingly the performance of large multinational clinical trials (MCT) with a common protocol. They must be planned when the demonstration of a hypothesis, which requires specific conditions (for example availability of patients with rare diseases, a particular infrastructure or expert knowledge in trial centers) has to be proven in an acceptable time. Our own experience has shown that such multinational trials are more time-consuming in their preparation and their analysis than multicenter trials which are run in one country. MCTs are associated with complex problems due to many differences in medical culture, treatment strategies, administrative guidelines, etc., between countries. When possible MCTs should be realized in countries and centers with relatively similar medical practices. A global coordination is necessary to control the progress of the trial in the different countries. The major requirements for the successful realisation of an MCT, from the writing of the first draft of the protocol until the publication of the results, are a well-coordinated multidisciplinary team and an effective project management.

Clinical Trials as Topic↗
PubMed1997

On the value of large multicenter drug intervention trials.

Many large multicenter clinical drug trials are outcome trials with several thousand patients, therefore also called megatrials, numerous of which encompassing the cardiovascular field. Usually designed to test and compare the efficacy of a specific therapy with the major aim being improved outcome at hard end-points, specifically morbidity and mortality, they are representative of typical intervention trials. Considering also the risk of failure, examples of large multicenter therapy trials are examined as to their value to the patients, the society, the health care providers, and--finally--also the manufacturers of the respective drugs. The 'Syst-Eur Trial' (Systolic Hypertension in Europe) representing a very recent intervention trial to treat isolated high systolic blood pressure in elderly patients with treatment based on a calcium channel blocker, nitrendipine (CAS 39562-70-4, Bayotensin, Baypress), serves to indicate that besides the major end-point results, here total stroke rate, a number of important additional efficacy and safety results may be obtained with large trials, such as in this case favourable data on total mortality, myocardial infarctions, cancer, bleeding.

Cardiovascular Agents↗
PubMed1991

Effect of the calcium antagonists nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal motility in man.

Nifedipine has been proven to be effective and safe in the treatment of primary oesophageal motility disorders which can cause angina-like chest pain and/or dysphagia. The effects of the calcium channel blockers nifedipine, nitrendipine, nimodipine and nisoldipine on oesophageal smooth muscle function in healthy male volunteers were studied by oesophageal manometry using the rapid pull-through-technique, in two randomized, double-blind crossover studies. Lower oesophageal sphincter pressure, oesophageal contraction amplitude and duration after a wet swallow (measured 5 cm and 10 cm above the lower oesophageal sphincter) were determined 30 min before and at 10 minute intervals up to 90 min after the administration of nimodipine and up to 120 min after nifedipine, nitrendipine and nisoldipine. The plasma drug concentration was measured at baseline (-15 min) and in parallel with the manometric measurements. Compared to placebo, lower oesophageal sphincter pressure was significantly decreased by 24% by nifedipine and 17% by nimodipine, whereas the effects of nitrendipine (decrease of 15%) and nisoldipine (9%) were not significant. Nifedipine significantly decreased by 17% the oral contraction amplitude compared to placebo and nimodipine by 11%. The duration of the contraction amplitudes was not altered. The decrease in sphincter pressure was correlated with the corresponding plasma drug levels of nifedipine r = 0.92, nitrendipine r = 0.80 and nisoldipine r = 0.79. Nimodipine showed no such correlation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Gastrointestinal receptors and drugs in motility disorders.

The review describes gastrointestinal receptors which are of therapeutic interest for the treatment of motility disorders. It updates the present knowledge on muscarinic, adrenergic, dopamine, opioid and dihydropyridine receptors, their subtypes, cellular sites and functional role as drug targets. On the basis of this pharmacological receptor concept, drugs like bethanechol, clonidine, lidamidine, metoclopramide, domperidone, cisapride, loperamide and nifedipine are evaluated in proven and potential indications. In view of the very complex regulation of motility, our understanding of receptors is still fragmentary and our tools to treat motility disorders do not fulfil all therapeutic requirements. This review tries to point out the areas of particular need for further basic research and the prospects of further drug development.

Calcium Channel Blockers↗
PubMed1991

Clinical efficacy of nifedipine and other calcium antagonists in patients with primary esophageal motor dysfunctions.

In this paper the pharmacodynamic effects of calcium channel blockers (verapamil, nifedipine, diltiazem, fendiline, nitrendipine, nimodipine, and nisoldipine) on esophageal motility in man and their clinical effects in patients with various forms of primary esophageal motility disorders are critically analysed and summarized. The evaluation of efficacy and safety is mainly focused on nifedipine (Bay a 1040, Adalat; CAS 21829-25-4), since it has been best documented clinical pharmacologically and therapeutically in this field. Nifedipine and--with varying potency--the other calcium antagonists reduce effectively the increased lower esophageal sphincter pressure (LESP) and abnormally high and prolonged peristaltic and nonperistaltic contractions in the esophageal body in patients with achalasia, diffuse esophageal spasm (DES), and other disorders which may cause angina-like chest pain and/or dysphagia. Pharmacodynamic effects on esophageal motility are closely correlated with the plasma concentration of nifedipine in healthy volunteers and in patients. However, a final judgement on the therapeutic value of these compounds in esophageal motor abnormalities cannot be given due to conflicting results from clinical studies with fairly small numbers of patients and varying study designs. Among the different calcium antagonists investigated nifedipine represents the best investigated and the most suitable compound for the treatment of primary hypertensive esophageal motor disorders.

Adolescent↗
PubMed1989

[Testing of drugs in humans. Current responsibilities and problems].

Despite the large number of drugs available, the development of new substances is necessary in view of the unsolved therapeutic problems, for example AIDS, cancer, rheumatoid diseases and disorders of the central nervous system such as Alzheimer's disease. More than ever before, the highest demands have to be made on the efficacy and safety of a new drug. The prerequisites for starting clinical trials in man, and the course of the phases of clinical development are described. Biometry has helped to improve the quality and thus the usefulness of clinical studies. Only in this way has it become possible to establish the superiority of one treatment over another on the basis of objective facts. The results of biometrically planned high-standard studies provide the basis for efficient and ethically justified drug development. They thus also have a direct impact on the fate of the patient.

Clinical Trials as Topic↗