Benchmarking R&D success rates of leading pharmaceutical companies: an empirical analysis of FDA approvals (2006-2022).

Previous analyses provide an industry benchmark of ∼10% for the success rate in clinical development. However, prior analyses were limited by a narrow timeframe, a diverse research focus, biases in phase-to-phase transition methodology or a focus on specific use cases. We calculated unbiased input:output ratios (Phase I to FDA new drug approval) to analyze the likelihood of first approval using data from clinicaltrials.

Ethanol perturbs lipid organization in models of stratum corneum membranes: An investigation combining differential scanning calorimetry, infrared and (2)H NMR spectroscopy.

Ethanol is used in a variety of topical products. It is known to enhance the permeability of the skin by altering the ability of the stratum corneum (SC) intercellular membranes to form an effective barrier. In addition, ethanol and other alcohols are key components of antiseptic gels currently used for hand wash.

Proton MRS of large multiple sclerosis lesions reveals subtle changes in metabolite T(1) and area.

The T(1) values of metabolites were measured in eight subjects with clinically definite multiple sclerosis (MS) having at least one large brain lesion (2.6 ± 0.7 mL) and in eight age- and sex-matched healthy controls.

Tangles of neurogenetics, neuroethics, and culture.

Neurogenetics promises rich insights into how the mind works. Researchers investigating the range of topics from normal brain functioning to pathological states are increasingly looking to genetics for clues on human variability and disease etiology. Is it fair to assume this interest in neurogenetics is universal? How should researchers and clinicians approach ideas of consent to research or prediction of disease when a subject or patient understands the mind with concepts or language incompatible with neurogenetics? In this paper we consider how non-Western philosophies bring complexity to ideas of individual and community consent and confidentiality in the context of neurogenetics.

Genetic counseling for early-onset familial Alzheimer disease in large Aboriginal kindred from a remote community in British Columbia: unique challenges and possible solutions.

A novel, pathogenic presenilin 1 (PS1) mutation has recently been identified in a large Aboriginal kindred living in dispersed communities throughout British Columbia, Canada. Disseminating genetic information and ensuring that appropriate genetic counseling services are provided to all concerned relatives have posed several unique challenges. These challenges include knowledge exchange and continuity of care in a geographically remote and culturally distinct community.

The functional roles of poly(ethylene glycol)-lipid and lysolipid in the drug retention and release from lysolipid-containing thermosensitive liposomes in vitro and in vivo.

Triggered release of liposomal contents following tumor accumulation and mild local heating is pursued as a means of improving the therapeutic index of chemotherapeutic drugs. Lysolipid-containing thermosensitive liposomes (LTSLs) are composed of dipalmitoylphosphatidylcholine (DPPC), the lysolipid monostearoylphosphatidylcholine (MSPC), and poly(ethylene glycol)-conjugated distearoylphosphatidylethanolamine (DSPE-PEG(2000)). We investigated the roles of DSPE-PEG(2000) and lysolipid in the functional performance of the LTSL-doxorubicin formulation.

Phase behavior of an equimolar mixture of N-palmitoyl-D-erythro-sphingosine, cholesterol, and palmitic acid, a mixture with optimized hydrophobic matching.

The phase behavior and lipid mixing properties of an equimolar mixture of nonhydroxylated palmitoyl ceramide (Cer16), palmitic acid (PA), and cholesterol have been investigated using 2H NMR and vibrational spectroscopy. This mixture is formed by the three main classes of lipids found in the stratum corneum (SC), the top layer of the epidermis, and provides an optimized hydrophobic matching. Therefore, its behavior highlights the role played by hydrophobic matching on the phase behavior of SC lipids.

Absolute metabolite concentrations calibrated using the total water signal in brain (1)H MRS.

Magnetic resonance spectroscopy (MRS) has been coupled with a multi-echo imaging sequence to determine the relaxation corrected signal areas of the metabolites and the tissue water. Stimulated echo acquisition mode (STEAM) spectra (TE/TM/TR 30/13.7/5000 ms) acquired from gray and white matter voxels in 43 healthy volunteers were fit using LCModel.

MR evidence of long T2 water in pathological white matter.

Purpose: To describe what, if any, specific long T(2)-related abnormalities occur in the white matter of subjects with either phenylketonuria (PKU) or multiple sclerosis (MS).

Materials And Methods: The 48-echo T(2) relaxation data (maximum TE = 1.12 sec) were acquired from 15 PKU subjects, 20 MS subjects, and 15 healthy volunteers.

Normal-appearing white matter in patients with phenylketonuria: water content, myelin water fraction, and metabolite concentrations.

Purpose: To prospectively assess relative water content (RWC), myelin water fraction (MWF), and hydrogen 1 magnetic resonance (MR) spectroscopy findings in the white matter (WM) of patients with phenylketonuria (PKU).

Materials And Methods: This study was approved by the institution's investigational review board, and informed consent was obtained. T2 water relaxation data were acquired by using a 48-echo measurement in a transverse plane through the genu and splenium of the corpus callosum in 16 patients (six men, 10 women; age range, 18-40 years) with PKU and 16 age- and sex-matched control subjects.

Universal behavior of membranes with sterols.

Lanosterol is the biosynthetic precursor of cholesterol and ergosterol, sterols that predominate in the membranes of mammals and lower eukaryotes, respectively. These three sterols are structurally quite similar, yet their relative effects on membranes have been shown to differ. Here we study the effects of cholesterol, lanosterol, and ergosterol on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine lipid bilayers at room temperature.

Proton T2 relaxation of cerebral metabolites of normal human brain over large TE range.

T2 of NAA, creatine and choline-containing compounds were measured in posterior frontal white matter and occipital grey matter in 10 healthy human volunteers. Decay curves comprised signals from eight TE times ranging from 30 to 800 ms with TR 2000 ms acquired with a PRESS sequence on a 1.5 T clinical scanner.

Proton T1 relaxation times of cerebral metabolites differ within and between regions of normal human brain.

Saturation recovery spectra (STEAM) were acquired at 1.5 T with 7 TRs ranging from 530 to 5000 ms and a constant TE of 30 ms in voxels (7.2 ml) located in occipital grey, parietal white and frontal white matter (10 subjects each location).