Why Do Adolescents Drink? Motivational Patterns Related to Alcohol Consumption and Alcohol-Related Problems

The present study was designed to investigate motivational patterns for drinking alcohol and their relation about alcohol consumption and problems related to alcohol consumption. Data were collected by semistructured interviews and questionnaires, containing questions about reasons for drinking, alcohol consumption, and problems related to alcohol consumption during the years 2001, 2004, and 2005. Three independent population samples from two different counties of central Sweden were included. A total of 11,167 adolescents participated. Data on reasons for drinking were analyzed by factor analysis to extract components explaining drinking motives. Relationships between motivational patterns and alcohol use were examined with correlation analysis. Three drinking motives emerged (social-enhancement, coping, and dominance motives) and related to alcohol consumption and problems related to alcohol consumption. Limitations of the study are noted and discussed.     

Adverse events and discomfort in studies on healthy subjects: the volunteer's perspective A survey conducted by the German Association for Applied Human Pharmacology

Objective: The various good clinical practice (GCP) guidelines do not define the volunteering subject as an active party. The present survey addresses the volunteer's perception of study-related inconvenience and risk and its impact on their decision to enrol. Methods: The survey consisted of a questionnaire to be filled out voluntarily and anonymously by healthy subjects who volunteered for enrolment in human pharmacology studies and who had participated in at least one previous study. Twenty-five categorised multiple-choice questions covered previous study experience, motives for volunteering, perception of and compliance with study directives and restrictions, past experience with adverse events, impact of the study environment on perceived well-being and the nature of adverse events likely to discourage them from enrolment. Results: Seven centres contributed by providing at least 30 (range 30–100) evaluable questionnaires. The database consists of a total of 440 healthy subjects (30.5% females, 69.5% males), from 18 to over 60 years of age. Two hundred and seven subjects (47.1%) were company employees and 233 (52.9%) were external volunteers. Eighty nine percent only participated in studies at one particular centre. Some 53.3% indicated financial motives, 27.8% `contribution to an improvement of pharmacotherapy', 12.7% `social responsibility', while 6.2% indicated other motives, mainly the opportunity of a free medical check-up. Thirteen subjects (3%) admitted to not answering correctly to the recruitment questions; this limited reliability is suspected to be even larger when the answer might preclude enrolment. From the volunteers' perspective, the environmental study conditions clearly appeared to have a highly relevant impact on their personal well-being. Some 17.1% of the subjects reported to have suffered adverse events occasionally and 2.7% frequently; but 14% admitted not reporting adverse events promptly and about 20% indicated that, with respect to previous adverse events, they first sought advice from other volunteers rather than from the investigator. Conclusions: Adverse events and inconveniences are inherent to nontherapeutic studies in healthy subjects. From the volunteer's perspective it appears that the incidence of adverse experiences in such studies exceeds the reported frequencies from investigators considerably. This finding suggests that investigators are usually not aware or able to ascertain the true incidence of adverse events. The present survey also confirms that pertinent information on the personal history may be unreliable. Volunteers are reluctant to answer questions regarding, in particular, their smoking habits, caffeine and alcohol consumption. Regarding the matter of informed consent, a noteworthy contradiction between the volunteers' attitude and behaviour became apparent. Although the volunteers admit that even rather minor adverse events ordinarily would discourage them, they still consent to enrolment. In view of this apparent contradiction, there is no alternative to the investigator's personal responsibility to counsel and protect the subject. Surveys such as this one may contribute to the awareness that the explicitness of GCP guidelines merely define the format, but not the content quality of these fundamental ethical values, which remain the unique burden and challenge of the investigator. Received: 17 March 1997 / Accepted in revised form: 20 June 1997     

Patients' knowledge of their condition and treatment: how it might be improved.

A study was carried out in which patients were asked questions to assess their knowledge of their condition and treatment, the questions relating particularly to care before siting an intravenous infusion and preoperative care. A high proportion of patients knew little about the procedure they were about to undergo. It is recommended that patients should be told more about matters relating to their condition and treatment. Written information could be given to supplement that given verbally by staff. A check list might be drawn up to ensure that patients receive all relevant information.     

Pharmacokinetics of amitriptyline infused intravenously in man

Summary Amitriptyline was given to four male volunteers by constant rate intravenous infusion. Blood samples were collected before, during and at various times after the infusion for estimation of the serum concentrations of amitriptyline. The level of nortriptyline never reached a detectable level. A two compartment open model was shown to be applicable to the data obtained. The meaning of the parameters obtained by a non-linear, least squares curve fitting procedure is discussed and the values are compared to those recently published for nortriptyline. The calculated biological half-life of amitriptyline was about 17 hours, a figure which differs considerably from previously calculated values for volunteers, but is in accordance with some newer results from patients.     

Are normal healthy research volunteers psychologically healthy? A pilot investigation

Most new drug development in Phase I clinical trials relies on the use of "normal healthy research volunteers" (NHRVs); however, little is known about the personality functioning of these volunteers. Determining whether NHRVs are similar to or different from individuals with "normal" personalities can impact participant recruitment, group assignment, and statistical interpretation of study results. This pilot study was undertaken to gain insight into the demographics, personality functioning, and potential psychopathology of the volunteers who participated in a Phase I confinement clinical drug trial. NHRVs (N=28) in an all-male, Phase I clinical trial completed a battery of questions, including the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and a sociodemographic questionnaire. Fifty percent of the sample showed clinically significant elevations on at least one of the scales. Current findings need to be replicated and expanded through future research. Results must be interpreted with caution because of the small, all-male sample. This preliminary study suggests that there is a difference in personality functioning between NHRVs and the general population. In addition, NHRVs may purposefully distort or conceal self-report information when participating in studies.     

Stabilization of psychophysical performance of healthy volunteers by propranolol—a contribution to differential psychopharmacology

Eight volunteers out of 81 medical students of a one-year register were selected in a two-step procedure by means of a motivation Q-sort. Of these, four were motivated for success (S.M.), whereas four were motivated for failure (F.M.). Following a stratification step, two subjects each from each group were orally given propranolol (0.6 mg/kg) or placebo in a double-blind trial. Test inventory; flicker fusion frequency; determination performance in normal and tailored testing; subjective self-rating; blood pressure; pulse. Evaluation was accomplished in the conventional dose-related way (propranolol versus placebo) and in a serum level oriented approach common in differential psychopharmacology, by judging the personality structure (nervousness, neuroticism, extraversion) and the volunteers' motivation. It was found that propranolol when compared to placebo did not alter the vigilance, performance and subjective assessment of the volunteers; hence, the next step of evaluation was made regardless of the treatment. The initial performance of F.M. subjects as measured on the determination test unit was substantially poorer when compared to S.M. volunteers. During a 7.5-h period after application, the reaction time of F.M. subjects was noted to improve both as a result of training due to repeated tests and as a function of propranolol. As only a small number of volunteers was available for the investigation, further studies are encouraged to verify performance of F.M. subjects.     

Open-label extension studies: do they provide meaningful information on the safety of new drugs?

The number of open-label extension studies being performed has increased enormously in recent years. Often it is difficult to differentiate between these extension studies and the double-blind, controlled studies that preceded them. If undertaken primarily to gather more patient-years of exposure to the new drug in order to understand and gain confidence in its safety profile, open-label extension studies can play a useful and legitimate role in drug development and therapeutics. However, this can only occur if the open-label extension study is designed, executed, analysed and reported competently. Most of the value accrued in open-label extension studies is gained from a refinement in the perception of the expected incidence of adverse effects that have most likely already been identified as part of the preclinical and clinical trial programme. We still have to rely heavily on post-marketing safety surveillance systems to alert us to type B (unpredictable) adverse reactions because open-label extension studies are unlikely to provide useful information about these types of often serious and relatively rare adverse reactions. Random allocation into test and control groups is needed to produce precise incidence data on pharmacologically expected, or type A, adverse effects. Some increased confidence about incidence rates might result from the open-label extension study; however, as these studies are essentially uncontrolled and biased, the data are not of great value. Other benefits have been proposed to be gained from open-label extension studies. These include ongoing access to an effective but otherwise unobtainable medicine by the volunteers who participated in the phase III pivotal trials. However, there are unappreciated ethical issues about the appropriateness of enrolling patients whose response to previous treatment is uncertain, largely because treatment allocation in the preceding randomised, double-blind, controlled trial has not been revealed at the time of entry into the open-label extension study. Negative aspects of open-label extension studies revolve around their use as a marketing tool, as they build a market for the drug and generate pressure for subsidised access to the drug from consumers and their physicians. Consumers, institutions where these studies are conducted and research ethics committees need to be convinced of the motives, as well as the quality, of the open-label extension study and its execution before supporting such studies. Open-label extension studies do have a legitimate but limited place in the clinical development of new medicines. The negative perceptions about these studies have arisen because of perversion of acceptable rationales for this type of study and a failure to recognise (or disclose) the limitations resulting from the inherent weaknesses in their design. Increased human exposure to a new medicine under reasonably controlled circumstances to increase confidence in the safety of the medicine is an acceptable rationale for an open-label extension study, and a useful activity to increase the knowledge of the safety profile of a new medicine. However, this goal is increasingly being achieved by means other than open-label extension studies.     

Pharmacokinetics of butobarbital after single and multiple oral doses in man

Summary A method is described for the assay of therapeutic levels of butobarbital (5-ethyl-5-n-butylbarbituric acid) in human plasma, which involves a single extraction step followed by gas chromatography with alkali flame ionization detection. The pharmacokinetics of butobarbital were studied in five healthy volunteers after oral administration of 200 mg. Plasma concentrations were determined at regular intervals up to 96 h and the data were fitted by non-linear, least squares regression analysis according to one-compartment kinetics. The average lag time was 0.11 h and the absorption half-life 0.21 h. The elimination half-life varied from 33.6 to 41.5 h with an average of 37.5 h. Four of the volunteers participated in a study of multiple dosing (every 24 h) during which substantial accumulation of butobarbital was observed. The elimination half-life after termination of drug administration had decreased to about 20–25% of its initial value, probably because of enzyme induction. It was concluded that butobarbital could not be regarded as a suitable drug for treatment of insomnia, since CNS depressant effects were likely to persist into the following day. Repeated administration of butobarbital should be avoided and its incidental use restricted to patients who require day-time sedation.     

Weight of financial reward in the decision by medical students and experienced healthy volunteers to participate in clinical trials

Summary The aim of this survey was twofold: to assess the willingness of medical students to volunteer for clinical trials and to evaluate the weight of the financial reward and other general details as seen by healthy volunteers who had already participated in clinical trials. A specific questionnaire was given to each group to be answered anonymously. Among the medical students only 2.9% had already volunteered, 39.7% said that they would never participate, 24.7% would do it for scientific interest, 32.2% for scientific interest and financial reward, and 4.2% for the financial reward alone. In experienced volunteers, financial reward was the main reason to participate (90%) followed by curiosity (6.3%). The financial reward actually received was considered adequate compensation for the time and discomfort by most of the volunteers (83.7%). The information supplied by the research team and the arrangements made to treat any hazardous event were considered adequate (47.5%) or optimal (42.5%). Almost all the experienced volunteers (93.8%) answered positively when asked about participation in future studies. The results show that financial reward is a very important reason for healthy volunteers to participate in clinical trials.