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Biomedical subjects

W M Wardell

Publications and source records attributed to W M Wardell.

15 recordsLinked to original sources
PubMed1979

Methodology for demonstrating sustained efficacy of hypnotics: a comparative study of triazolam and flurazepam.

To test for sustained hypnotic efficacy, triazolam (0.6 mg) or flurazepam (30 mg) was given to chronic insomniac patients for 7 consecutive nights in parallel, double-blind design. Triazolam at this dose was an effective hypnotic by all usual subjective measures and did not produce appreciable hangover. Flurazepam performed similarly. For either drug, comparison of the mean scores for the first 2 nights with that for the last 2 nights for any of the parameters did not reveal any significant difference. Thus, both triazolam and flurazepam showed sustained efficacy for 1 week at these doses. Some interesting theoretical and practical questions about the measurement of sustained efficacy of hypnotics in situations of repetitive dosing were addressed by the study. While a placebo control is desirable, the results obtained may be uninterpretable. An acute-care hospital setting may not be the ideal setting for doing such studies. There were indications from the study that the first-night results in a hypnotic clinical trial may be atypical.

Adult↗
PubMed1978

The rate of development of new drugs in the United States, 1963 through 1975.

Information was obtained on 1,103 new chemical entities (NCEs) first tested in man from 1963 through mid-1975 by 36 U. S.-owned and 10 foreign-owned pharmaceutical companies operating in the U. S. Of these NCEs 1,029 reached the stage of IND filing. The portion of the U. S. industry responsible for the NCEs was relatively concentrated; 7 of the 36 companies accounted for half of the NCEs and 4 of these accounted for one-third. Although the annual worldwide rate of testing of NCEs by U. S. companies appeared to rise and then fall from 1963 through 1966, since 1966 the rate has been fairly constant. With time, however, a higher proportion of U. S.-owned NCEs is being first studied in man abroad. The annual rate of IND filings for U. S.-owned NCEs generally declined from 1965 to 1972, whereas the rate was fairly constant for foreign-owned NCEs over the entire period. The overall success rate in drug development has been low; nearly 90% of the NCEs studied in man are dropped prior to NDA submission, but about 88% of the NDAs submitted are approved for market. The 1974-1975 data indicate that the mean durations of the IND and NDA phase were then 4 and 2 years, respectively. However, there were variations in the time required for DNA approval between different pharmacologic areas. The data described in this paper represent the first baselines against which future trends in the processes of drug development and approval can be measured.

Chemistry, Pharmaceutical↗
PubMed1978

The drug lag revisited: comparison by therapeutic area of patterns of drugs marketed in the United States and Great Britain from 1972 through 1976.

This study describes rates and patterns of new drug introductions in the U.S. and Britain from January, 1972, through December, 1976, updating an earlier study that described the patterns over the previous decade. This comparative international approach enables overall effects of different regulatory, industrial, and other types of changes in drug research and development in the two countries to be evaluated. Numerical differences persisted. In the 1972 to 1976 period, 82 new drugs appeared for the first time in either country. Only 29% of these became mutually available in both countries, 2.4 times as many becoming available first in Britain as in the U.S. Of the 71% that became exclusively available, 2.6 times as many became available in Britain as in the U.S. More important than numerical data are clinical implications of differences between the countries. The largest differences have narrowed since the previous study, but important categories in which the U.S. still lagged behind Britain in December, 1976, included cardiovascular drugs, peptic ulcer drugs, and central nervous system drugs--including therapies for depression, epilepsy, and migraine. Several factors contributed to the narrowing of U.S.--British therapeutic differences, including more realistic regulatory practices and higher quality clinical studies in the U.S., more conservative practices in Britain, attention drawn by previous studies to anachronisms in the U.S., and industrial changes such as more efficient penetration of the U.S. market by foreign firms. It is difficult to determine the relative contribution of each of these factors to the narrowing of the international difference.

Analgesics↗
PubMed1977

Analgesic efficacy of an orally administered combination of pentazocine and aspirin. With observations on the use and statistical efficiency of GLOBAL subjective efficacy ratings.

The analgesic efficacy of a combination of pentazocine and aspirin (PA) in the ration 1:13 was compared with that of 650 mg of aspirin alone (A650) and with placebo (PBO), in 98 patients with postoperative pain. Two dose levels of the combination were compared: the lower dose (PA-L) consisted of pentazocine 25 mg and aspirin 325 mg, while the higher dose (PA-H) consisted of pentazocine 50 mg and aspirin 650 mg. All active treatments performed significantly better than PBO. PA-L performed as well as A650, while PA-H performed significantly better than A650. In addition to the usual subjective measures of analgesia, we obtained in 74 patients an evaluation of the overall (GLOBAL) performance of the treatment. This was rated on an ordinal scale of 1 ("poor") to 5 ("excellent"). On the GLOBAL scale, PBO had a mean score of 2.4 (fair-good); A650 and PA-L had scores of 3.6 and 3.9 respectively (good-very good): and PA-H had a score of 4.5 (very good-excellent). In five of six comparisons between treatment means, GLOBAL had the best discriminating power of all six measures. In the two comparisons of greatest interest (A650 against PBO and PA-H against A650), GLOBAL was more than twice as efficient as the TOTAL (summed pain score) measure. In comparing the statistical efficiency of different measures of the same analgesic effect, there is a problem in determining what are "clinically equivalent differences" on the various analgesic scales employed. We propose the use of the observed sample differences and the safeguard of repeating the comparisons over several studies to minimize the effect of random-origin bias.

Adult↗