Developing Drug Products in an Aging Society

This book aims to address the major aspects of future drug product development and therapy for older adults, giving practical guidance for the rational product and clinical development and prescribing of drug products to older patients. The book wil provide valuable information for students, scientists, regulators, practitioners and industry. Sven Stegeman is the editor of the book entitled Developing Drug Products in an Aging Society. Paul Jansen from Ephor has contributed with a chapter to the book. The costs of the e-book are 190,39 euro and hard-cover 242,74 euro. Publisher Springer, ISBN 978-3-319-43097-3.

Haloperidol and risperidon not effective for delirium in palliative care

A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services  to relieve symptoms of delirium. Risperidone or haloperidol were compared to placebo in patients with a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95%CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95%CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95%CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95%CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95%CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95%CI, 0.91-1.84; P = .14). CONCLUSIONS AND RELEVANCE In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.

Agar et al. JAMA Intern Med. doi:10.1001/jamainternmed.2016.7491 Published online December 5, 2016.

Vitamin D and functional performance studie in thesis

The results of the thesis of Christiaan Oudshoorn indicate that vitamin D deficiency is still prevalent among older individuals and that knowledge among older individuals about vitamin D is poor. With regard to functional performance an association between vitamin D status and muscle performance in both men and women was demonstrated. High dose vitamin D supplementation improves neuromuscular function (gait speed and TUGT performance) and is well tolerated. In addition associations were also observed with cognitive performance and vascular function.

The thesis is available on this website under research/thesis

Studies towards optimization of pharmacotherapy in good progress

Two randomized controlled trials (RCTs) towards optimization of pharmacotherapy in old patients, the SENATOR and OPERAM study, are well in progress. The SENATOR study have included about 200 patients and the OPERAM study will start the inclusion period on time in December. The RCTs use software supported methods, which include also the STOPP/START criteria. The aim of the studies is to avoid the prescription of inappropriate medicines and avoidable adverse drug reactions.

A survey of geriatric expertise in medicines evaluation at national regulatory agencies in Europe: There is still room for improvement!

On behalf of the EUGMS Pharmacology Special Interest Group Perehudoff, Petrovic, O’Neill and Cherubini investigated geriatric medicine input in national regulatory medicine licensing agencies across Europe. A questionnaire was mailed to 22 national regulatory agencies in 2014. Currently only one agency (6%), i.e. the Swedish Medicines Authority, has a specific committee to evaluate medicines for older people, while previously, 2/21 agencies (10%) had a specific committee to assess medicines used by older people. The Swedish and Dutch regulatory agencies (13%) have binding policy on how to assess medicines for older people. On the other hand, nine national agencies (56%) follow external policies for the evaluation of geriatric medicines. Six agencies (38%) follow a policy concerning the inclusion of older people in clinical trials. Eight agencies (50%) have at least one geriatrician on their medical advisory boards, although this position is permanent at only three of them. Twelve agencies (75%) have access to ad-hoc geriatric advice. Compared to the previous survey, 6/21 agencies (28%) had a geriatrician on their medical advisory boards and 10/21 (48%) agencies provided for ad-hoc input of geriatricians into advisory board discussions. Finally, three regulatory authorities (19%), involve geriatricians in research on drug prescription in older people. This survey demonstrates that, despite some improvement from the previous investigation, there is still a need for promoting a greater involvement of geriatric expertise in medicines evaluation across Europe.

Th article is published in the Journal European Geriatric Medicine Doi : 10.1016/j.eurger.2016.07.003

Adjudication ADR OPERAM study

The OPERAM study, towards optimization of polypharmacy with support of the STRIP method and the STRIPassistant, has finished the protocol and will start at the end of this year with the inclusion of the first patients. At the EUGMS a poster is presented of the adjudication of the ADR. The postar is available at this website at Abstracts and Posters

Method to calculate time to benefit

Esther van der Glind and co-authors have developed a method to calculate the time to benefit. They used statistical process control (SPC), a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. The open access article is published in Drugs and Aging 2016, 33:347–353. The article is available on this website (see Research/articles).

Treat me as an old lady or an old gentleman

Ephor gives support to the “treatment as a lady” slogan.  Especially the appropriate treatment of an old lady is of importance. Elderly women are using large amounts of medicines. They deserve to be included in trials to avoid the wrong dose and severe adverse effects after the authorization of the drug. This is also the case for elderly men. There is also a need for research in old men in diseases common in women as osteoporosis. Personalized medicine is of importance, however don’t forget to avoid harm in old persons.

Vitamine D dose is of importance

High-dose vitamin D supplementation does not improve lower-extremity function and increases the risk for falls among elderly adults. This  is the result of a randomized clinical trial of 200 men and women aged 70 or older who had experienced at least one low-trauma fall in the prior year. Two high vitamin D doses monthly were compared with a standard dose of 24,000 IU of vitamin D3 per month (equivalent to the currently recommended 800 IU per day). Subjects taking the higher doses showed no improvements in lower-extremity function and were more likely to have a second fall (P = .048) in the subsequent year.

The study is published online January 4 in JAMA Internal Medicine by Heike A Bischoff-Ferrari, from the University Hospital of Zurich, Switzerland, and colleagues.

Medication review with STRIP-assistant costs 10 minutes

In a randomized controlled trial, towards computerized medication reviews with the STRIP-assistant, the authors hypothesize that having a group of users perform a similar task over a prolonged period of time will lead to improvements in efficiency of that task. Three expert teams, consisting of an independent physician and an independent pharmacist, conducted 150 computerized medication reviews on patients in 13 general practices located in Amsterdam, the Netherlands. The average time in minutes required to conduct medication reviews up to the first quartile was 20 minutes (SD = 9.00), while the time from the third quartile up was 10 minutes (SD = 6.13). This leads the authors to conclude that the amount of time users needed to perform similar tasks decreased significantly as they gained experience over time. The article is available at this website (see Research/Articles).