A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - An application for paediatric dosage form selection

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy.     

Acceptability of Potential Rectal Microbicide Delivery Systems for HIV Prevention: A Randomized Crossover Trial

We assessed the acceptability of three of over-the-counter products representative of potential rectal microbicide (RM) delivery systems. From 2009 to 2010, 117 HIV-uninfected males (79 %) and females (21 %) who engage in receptive anal intercourse participated in a 6-week randomized crossover acceptability trial. Participants received each of three products (enema, lubricant-filled applicator, suppository) every 2 weeks in a randomized sequence. CASI and T-ACASI scales assessed product acceptability via Likert responses. Factor analysis was used to identify underlying factors measured by each scale. Random effects models were fit to examine age and gender effects on product acceptability. Three underlying factors were identified: Satisfaction with Product Use, Sexual Pleasure, and Ease of Product Use. For acceptability, the applicator ranked highest; however, differences between product acceptability scores were greatest among females and younger participants. These findings indicate that RM delivery systems impact their acceptability and should be considered early in RM development to enhance potential use.     

The effects of suggestions of altertness in hypnosis on pupillary response: Report on a single subject

The pupil size of a single S was recorded under 2 types of hypnotic suggestion: alertness instructions and traditional relaxation instructions. It was found that the size of the pupil increased significantly under alertness instructions. This result was taken as further corroboration of the hypothesis that changes in various parameters of arousal apparently associated with hypnosis may be attributed to specifiable characteristics of the instructions used rather than to stable characteristics of the “state” of hypnosis.     

Is anterior resection of the rectosigmoid safe after preoperative radiation?

Forty patients with carcinoma of the rectum or rectosigmoid underwent preoperative irradiation, followed by anterior resection with anastomosis. The radiation dose was 4500 rads administered in 25 fractions over a period of five weeks. One to three weeks after the radiation was completed, anterior resection of the rectosigmoid with anastomosis was done. Of the 40 patients, 23 had hand-sewn anastomoses and 17 had EEA stapled anastomoses. Fourteen of the 40 had diverting loop colostomies, all colostomies were subsequently closed, and there were no clinical postoperative anastomotic leaks. Anterior resection and anastomosis are considered to be technically safe with the surgical and radiation techniques used. Read at the joint meeting of the American Society of Colon and Rectal Surgeons with the Section of Colo-Proctology, Royal Society of Medicine, and the Section of Colonic and Rectal Surgery, Royal Australasian College of Surgeons, New Orleans, Louisiana, May 6 to 11, 1984.