Provision of information about drug side-effects to patients

To make informed decisions about taking medicinal drugs, people need accurate information about side-effects. A European Union guideline now recommends use of qualitative descriptions for five bands of risk, ranging from very rare (affecting < 0·01% of the population), to very common (>10%). We did four studies of more than 750 people, whom we asked to estimate the probability of having a side-effect on the basis of qualitative and quantitative descriptions. Our results showed that qualitative descriptions led to gross overestimation of risk. Until further work is done on how patients taking the drugs interpret these terms, the terms should not be used in drug information leaflets.

Communicating information about medication side effects: effects on satisfaction, perceived risk to health, and intention to comply

Previous research has shown that people's evaluations of explanations about medication and their intention to comply with the prescription are detrimentally affected by the inclusion of information about adverse side effects of the medication. The present study (Experiment 1) examined which particular aspects of information about side effects (their number, likelihood of occurrence, or severity) are likely to have the greatest effect on people's satisfaction, perception of risk, and intention to comply, as well as how the information about side effects interacts with information about the severity of the illness for which the medication was prescribed. Across all measures, it was found that manipulations of side effect severity had the greatest impact on people's judgements, followed by manipulations of side effect likelihood and then number. Experiments 2 and 3 examined how the severity of the diagnosed illness and information about negative side effects interact with two other factors suggested by Social Cognition models of health behaviour to affect people's intention to comply: namely, perceived benefit of taking the prescribed drug, and the perceived level of control over preventing or alleviating the side effects. It was found that providing people with a statement about the positive benefit of taking the medication had relatively little effect on judgements, whereas informing them about how to reduce the chances of experiencing the side effects had an overall beneficial effect on ratings.

Is 15 per cent very common? Informing people about the risks of medication side effects

Objectives - To assess the general public's interpretation of the verbal descriptors for side effect frequency recommended for use in medicine information leaflets by a European Union (EU) guideline, and to examine the extent to which differences in interpretation affect people's perception of risk and their judgments of intention to comply with the prescribed treatment. Method - Two studies used a controlled empirical methodology in which people were presented with a hypothetical, but realistic, scenario about visiting their general practitioner and being prescribed medication. They were given an explanation that focused on the side effects of the medicine, together with information about the probability of occurrence using either numerical percentages or the corresponding EU verbal descriptors. Interpretation of the descriptors was assessed. In study 2, participants were also required to make various judgments, including risk to health and intention to comply. Key findings - In both studies, use of the EU recommended descriptors led to significant overestimations of the likelihood of particular side effects occurring. Study 2 further showed that the "overestimation" resulted in significantly increased ratings of perceived severity of side effects and risk to health, as well as significantly reduced ratings of intention to comply, compared with those for people who received the probability information in numerical form. Conclusion - While it is recognised that the current findings require replication in a clinical setting, the European and national authorities should suspend the use of the EU recommended terms until further research is available to allow the use of an evidence-based approach.

Comparison of two methods of presenting risk information to patients about the side effects of medicines

Objective: To determine whether the use of verbal descriptors suggested by the European Union (EU) such as "common" (1-10% frequency) and "rare" (0.01-0.1%) effectively conveys the level of risk of side effects to people taking a medicine. Design: Randomised controlled study with unconcealed allocation. Participants: 120 adults taking simvastatin or atorvastatin after cardiac surgery or myocardial infarction. Setting: Cardiac rehabilitation clinics at two hospitals in Leeds, UK. Intervention: A written statement about one of the side effects of the medicine (either constipation or pancreatitis). Within each side effect condition half the patients were given the information in verbal form and half in numerical form (for constipation, "common" or 2.5%; for pancreatitis, "rare" or 0.04%). Main outcome measure: The estimated likelihood of the side effect occurring. Other outcome measures related to the perceived severity of the side effect, its risk to health, and its effect on decisions about whether to take the medicine. Results: The mean likelihood estimate given for the constipation side effect was 34.2% in the verbal group and 8.1% in the numerical group; for pancreatitis it was 18% in the verbal group and 2.1% in the numerical group. The verbal descriptors were associated with more negative perceptions of the medicine than their equivalent numerical descriptors. Conclusions: Patients want and need understandable information about medicines and their risks and benefits. This is essential if they are to become partners in medicine taking. The use of verbal descriptors to improve the level of information about side effect risk leads to overestimation of the level of harm and may lead patients to make inappropriate decisions about whether or not they take the medicine.

Expressing medicine side effects: assessing the effectiveness of absolute risk, relative risk, and number needed to harm, and the provision of baseline risk information

Objective: To assess the effectiveness of absolute risk, relative risk, and number needed to harm formats for medicine side effects, with and without the provision of baseline risk information. Methods: A two factor, risk increase format (relative, absolute and NNH) x baseline (present/absent) between participants design was used. A sample of 268 women was given a scenario about increase in side effect risk with third generation oral contraceptives, and were required to answer written questions to assess their understanding, satisfaction, and likelihood of continuing to take the drug. Results: Provision of baseline information significantly improved risk estimates and increased satisfaction, although the estimates were still considerably higher than the actual risk. No differences between presentation formats were observed when baseline information was presented. Without baseline information, absolute risk led to the most accurate performance. Conclusion: The findings support the importance of informing people about baseline level of risk when describing risk increases. In contrast, they offer no support for using number needed to harm. Practice implications: Health professionals should provide baseline risk information when presenting information about risk increases or decreases. More research is needed before numbers needed to harm (or treat) should be given to members of the general populations. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Communicating risk of medication side effects: an empirical evaluation of EU recommended terminology

Two experiments compared people's interpretation of verbal and numerical descriptions of the risk of medication side effects occurring. The verbal descriptors were selected from those recommended for use by the European Union (very common, common, uncommon, rare, very rare). Both experiments used a controlled empirical methodology, in which nearly 500 members of the general population were presented with a fictitious (but realistic) scenario about visiting the doctor and being prescribed medication, together with information about the medicine's side effects and their probability of occurrence. Experiment 1 found that, in all three age groups tested (18 - 40, 41 - 60 and over 60), participants given a verbal descriptor (very common) estimated side effect risk to be considerably higher than those given a comparable numerical description. Furthermore, the differences in interpretation were reflected in their judgements of side effect severity, risk to health, and intention to comply. Experiment 2 confirmed these findings using two different verbal descriptors (common and rare) and in scenarios which described either relatively severe or relatively mild side effects. Strikingly, only 7 out of 180 participants in this study gave a probability estimate which fell within the EU assigned numerical range. Thus, large scale use of the descriptors could have serious negative consequences for individual and public health. We therefore recommend that the EU and National authorities suspend their recommendations regarding these descriptors until a more substantial evidence base is available to support their appropriate use.

Students’ perception of the safety and value of a herbal vs. a conventional medicine for treating insomnia

University students suffer from variable sleep patterns including insomnia;[1] furthermore, the highest incidence of herbal use appears to be among college graduates.[2] Our objective was to test the perception of safety and value of herbal against conventional medicine for the treatment of insomnia in a non-pharmacy student population. We used an experimental design and bespoke vignettes that relayed the same effectiveness information to test our hypothesis that students would give higher ratings of safety and value to herbal product compared to conventional medicine. We tested another hypothesis that the addition of side-effect information would lower people’s perception of the safety and value of the herbal product to a greater extent than it would with the conventional medicine.

The imminent availability of a potent weight-loss medicine in pharmacies: public perception of effectiveness

Orlistat is an effective weight-loss medicine, which will soon be available for purchase in pharmacies. We used a factorial experiment and found that informing people about the availability for purchase of this medicinal product previously only available on prescription resulted in higher ratings of perceived value and effectiveness compared to a natural health supplement even though we used the same statement about effectiveness. This positive perception of orlistat was not impaired by the provision of side-effect information. Orlistat will soon be available in pharmacies. Health professionals must act to prevent its misuse by those not overweight.

Interpretation of recommended risk terms: differences between doctors and lay people

Objectives: To examine doctors' (Experiment 1) and doctors' and lay people's (Experiment 2) interpretations of two sets of recommended verbal labels for conveying information about side effects incidence rates. Method: Both studies used a controlled empirical methodology in which participants were presented with a hypothetical, but realistic, scenario involving a prescribed medication that was said to be associated with either mild or severe side effects. The probability of each side effect was described using one of the five descriptors advocated by the European Union (Experiment 1) or one of the six descriptors advocated in Calman's risk scale (Experiment 2), and study participants were required to estimate (numerically) the probability of each side effect occurring. Key findings: Experiment 1 showed that the doctors significantly overestimated the risk of side effects occurring when interpreting the five EU descriptors, compared with the assigned probability ranges. Experiment 2 showed that both groups significantly overestimated risk when given the six Calman descriptors, although the degree of overestimation was not as great for the doctors as for the lay people. Conclusion: On the basis of our findings, we argue that we are still a long way from achieving a standardised language of risk for use by both professionals and the general public, although there might be more potential for use of standardised terms among professionals. In the meantime, the EU and other regulatory bodies and health professionals should be very cautious about advocating the use of particular verbal labels for describing medication side effects.

Over the counter medicines and the need for immediate action: a further evaluation of European Commission recommended wordings for communicating risk

A study examined people's interpretation of European Commission (EC) recommended verbal descriptors for risk of medicine side effects, and actions to take if they do occur. Members of the general public were presented with a fictitious (but realistic) scenario about suffering from a stiff neck, visiting the local pharmacy and purchasing an over the counter (OTC) medicine (Ibruprofen). The medicine came with an information leaflet which included information about the medicine's side effects, their risk of occurrence, and recommended actions to take if adverse effects are experienced. Probability of occurrence was presented numerically (6%) or verbally, using the recommended EC descriptor (common). Results showed that, in line with findings of our earlier work with prescribed medicines, participants significantly overestimated side effect risk. Furthermore, the differences in interpretation were reflected in their judgements of satisfaction, side effect severity, risk to health, and intention to take the medicine. Finally, we observed no significant difference between people's interpretation of the recommended action descriptors ('immediately' and 'as soon as possible'). (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Cannabidivarin is anticonvulsant in mouse and rat in vitro and in seizure models

Summary Background and purpose: Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models. Experimental approach: The effect of CBDV (1-100μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4-AP application or Mg2+-free conditions was assessed by in vitro multi-electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50-200 mg kg-1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine-induced seizures in rat. CBDV effects in combination with commonly-used antiepileptic drugs were investigated in rat seizures. Finally, the motor side effect profile of CBDV was investigated using static beam and gripstrength assays. Key results: CDBV significantly attenuated status epilepticus-like epileptiform LFPs induced by 4-AP and Mg2+-free conditions. CBDV had significant anticonvulsant effects in mES (≥100 mg kg-1), audiogenic (≥50 mg kg-1) and PTZ-induced seizures (≥100 mg kg-1). CBDV alone had no effect against pilocarpine-induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at 200 mg kg-1 CBDV. CBDV had no effect on motor function. Conclusions and Implications: These results indicate that CBDV is an effective anticonvulsant across a broad range of seizure models, does not significantly affect normal motor function and therefore merits further investigation in chronic epilepsy models to justify human trials.

Increasing doxorubicin activity against breast cancer cells using PPARγ-ligands and by exploiting circadian rhythms

Doxorubicin is effective against breast cancer, but its major side effect is cardiotoxicity. The aim of this study was to determine whether the efficacy of doxorubicin on cancer cells could be increased in combination with PPARγ agonists or chrono-optimization by exploiting the diurnal cycle. We determined cell toxicity using MCF-7 cancer cells, neonatal rat cardiac myocytes and fibroblasts in this study. Doxorubicin damages the contractile filaments of cardiac myocytes and affects cardiac fibroblasts by significantly inhibiting collagen production and proliferation at the level of the cell cycle. Cyclin D1 protein levels decreased significantly following doxorubicin treatment indicative of a G1 /S arrest. PPARγ agonists with doxorubicin increased the toxicity to MCF-7 cancer cells without affecting cardiac cells. Rosiglitazone and ciglitazone both enhanced anti-cancer activity when combined with doxorubicin (e.g. 50% cell death for doxorubicin at 0.1 μM compared to 80% cell death when combined with rosiglitazone). Thus, the therapeutic dose of doxorubicin could be reduced by 20-fold through combination with the PPARγ agonists, thereby reducing adverse effects on the heart. The presence of melatonin also significantly increased doxorubicin toxicity, in cardiac fibroblasts (1 μM melatonin) but not in MCF-7 cells. Our data show, for the first time, that circadian rhythms play an important role in doxorubicin toxicity in the myocardium; doxorubicin should be administered mid-morning, when circulating levels of melatonin are low, and in combination with rosiglitazone to increase therapeutic efficacy in cancer cells while reducing the toxic effects on the heart.

Technical note: Organics-induced fluorescence in Raman studies of sulfuric acid aerosols

Fluorescence is a troublesome side effect in laboratory Raman studies on sulfuric acid solutions and aerosol particles. We performed experiments showing that organic matter induces fluorescence in H2SO4/H2O solutions. The intensity of the fluorescence signal appears to be almost independent of the concentration of the organic substances, but depends strongly on the sulfuric acid concentration. The ubiquity of organic substances in the atmosphere, their relatively high abundance, and the insensitivity of the fluorescence with respect to their concentrations will render most acidic natural aerosols subject to absorption and fluorescence, possibly influencing climate forcing. We show that, while fluorescence may in the future become a valuable tool of aerosol diagnostics, the concurrent absorption is too small to significantly affect the atmosphere's radiative balance.