Clinical Trials Of New Drugs Research Articles

Tim Tucker—Director of the South African AIDS Vaccine Initiative

Tim Tucker graduated in medicine from the University of Cape Town (UCT) in 1991. Following an internship at the Groote Schuur Hospital in 1992, he became a Clinical Research Fellow at the Medical Research Council's (MRC) Liver Research Center at UCT for the next 4 years. As well as being responsible for treating patients with viral hepatitis, he was involved in phase 1, 2, and 3 clinical trials for new drugs, and therapeutic vaccine trials for patients with chronic hepatitis B and C. From 1997–2001, he worked in the Clinical Virology department at the Groote Schuur Hospital and during this time, completed a PhD assessing the molecular epidemiology and tropism of the hepatitis G virus (also known as GBV-C). His research interests include HIV, hepatitis viruses, and human papillomavirus (HPV). After a brief stint examining the role of amniotic fluid in HIV mother-to-child transmission, he became the Director of the South African AIDS Vaccine Initiative (SAAVI) in 2001, a position he holds today.

The shifting functional balance of patents and drug regulation.

Patents are often portrayed as the necessary reward to compensate pharmaceutical firms for the huge costs and risks associated with Food and Drug Administration (FDA)-mandated clinical trials of new drugs. But the relationship between the patent system and other regulation of drugs is more complex than this simple formulation suggests. Drug regulation operates in tandem with patents to make proprietary products profitable, and patents themselves increasingly threaten to limit profitability by diverting profits elsewhere. At the same time, resistance to high drug prices is prompting new state and federal regulatory initiatives that threaten to reduce the value of drug patents. The distinctive intertwining of patents with other regulatory regimes and the shifting role of patents in the biopharmaceutical sector call into question how this singular success story for innovation policy will play out in the future.

Company News

Shanghai Roche Adopts Siebel eBusiness Applications. Trimedyne Commences Sales in China. HK's Healthy International to Distribute US Baywood Products for the Asia Pacific. Exactech Opens Total Joint Replacement Clinics in China. NexMed's New Erectile Dysfunction Product Launched in China. Singapore Key to Agilent's R&D. Yamanouchi Ties-up with Celera Genomics. Korean Firm Gets FDA Nod for Clinical Trials of New Drugs. Dr. Reddy's Gets Approval to Market Its First Biotech Product. Nicholas Piramal and Reckitt Benckiser Joint Venture Called Off. China's Largest Gene Company Applies for 3700 Patents. Syncor Acquires Australia's Radpharm Scientific. Prana Biotech Develops Potential Cure for Alzheimer's Disease. Progen Enters Into Phase II Trial of Anti-Cancer Drug. Ranbaxy Acquires Indian Herbal Brands. Sumitomo to Commercialize Novirio's Hepatitis B Drug.

Old World News: The Monopoly Stage of Capitalism

Fifteen years ago I wrote in the Bulletin of Medical Ethics of bioethical imperialism. I was annoyed by the attempt of a group of American bioethicists to set up a European Center of Bioethics, without reference to the many Europeans already working in the field. Although one American friend reminds me of the expression every time we talk, it was not until recently that I heard others using it, and in some anger. The occasion was a conference set up by the World Medical Association, in Pretoria, South Africa, at the end of March this year, to discuss the latest version of the Helsinki Declaration. The current version of the Declaration was accepted unanimously by the forty-four national medical associations, including the American Medical Association, that attended the World Medical Assembly in Edinburgh last October. It is substantially different from previous versions because it now gives primacy to the interests of research subjects. The whole Declaration is designed to support its fifth paragraph: In medical research on human subjects, considerations related to the well-being of the human subject should take precedence over the interests of science and society. The changes have led to fierce debate, particularly in the pharmaceutical industry and among drug regulators. The new version requires much greater openness: it requires, for instance, that information about sources of funding or potential conflicts of interest be disclosed to IRBs and to subjects, that the design of all studies be publicly available, and that the results of all studies be published or otherwise made publicly available, whatever the findings. It was to discuss requirements such as these, and how to achieve them in practice, that experts from twenty countries gathered in Pretoria this March. Many of us came away disappointed, however, as a small American group effectively hijacked the conference by constantly returning discussion to the question of paragraph 29 of the Declaration. This paragraph requires that new therapies be tested against the best current methods; it also states that the requirement not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic method exists. The argument, from the U.S. Food and Drug Administration in particular, is that new drugs should always be tested against placebo unless not providing active treatment would run the risk (whose magnitude the FDA does not define) of leaving the subject dead or permanently disabled. Bob Temple, the man from the feds who always leads for them on this subject, uses a splendidly nihilistic argument. He says that you cannot use active controls in randomized clinical trials of new drugs because you do not know their precise effect in that particular trial population. …

Participation of Hospital Pharmacists in the Selection of Drugs Restricted in Concomitant Use with a New Investigational Drug in Clinical Trials

If drugs that must be restricted in their concomitant use with a new investigational drug are not accurately chosen, then both the ethical and scientific objectives can not be sufficiently achieved in clinical trials of new drugs. We compared the differences between the drug selections made sponsor and by a hospital pharmacist for all drugs (2, 093 drugs) adopted by Osaka Medical College Hospital.Accurate selections were made in 215.82±130.21 instances of drug use by the hospital pharmacist, but only in 151.77±105.45 instances of drug use by the sponsor. The number of accurate selections by the hospital pharmacists was significantly lager than that of sponsor (P<0.05). Furthermore, the hospital pharmacist selected drugs that were unnecessary in the protocol in only 1.91±8.95 instances of drug use, while the sponsor did so in 5.59±7.97 articles. The number of unnecessary selections by the hospital pharmacists was therefore significantly smaller than that of the sponsor (P<0.01).These results demonstrate that the ability of hospital pharmacists appears to be superior to that of the sponsor in selecting drugs which have certain restrictions. These findings thus indicate that hospital pharmacists possess sufficient drug information regarding the pharmacological action, drug interaction and pharmacodynamics of most drugs.We therefore maintain that hospital pharmacists should thus play an important role in drafting the protocol of clinical trials for new drugs. If hospital pharmacists are involved, then such clinical trials will be both more effective and more accurate.

Pharmacologic insights into the future of trastuzumab

A combination of factors has been responsible for improvements in cancer survival and cure rates. In addition to new therapies with novel/genetic targets, these include improvements in drug delivery, new schedules/sequencing of drug administration and the identification of combination therapies with greater activity/dose density than existing regimens. The recognition that such criteria can affect treatment outcome has led to their incorporation into clinical trials of new drugs. Furthermore, pharmacokinetic and pharmacodynamic parameters have become increasingly important for the rational selection of dose, administration route and schedule. The humanized monoclonal antibody trastuzumab (Herceptin) has been rationally developed to target the human epidermal growth factor receptor-2 (HER2), which is overexpressed in 20%-30% of breast cancers and is associated with poor prognosis. Trastuzumab when administered i.v. on a weekly schedule either alone or in combination with taxanes, improves survival of women with HER2-positive metastatic breast cancer. Based upon pharmacokinetic considerations, current studies are examining whether trastuzumab can be administered i.v. every three weeks or by the s.c. route. These regimens would have advantages for patients and medical staff in terms of acceptability, ease of administration and, potentially, cost effectiveness. Furthermore, various combinations of trastuzumab and chemotherapeutic agents are being explored with the aim of identifying the optimal combination regimen for clinical use. The rationale for these various studies and the studies themselves are described.

Epilepsy, vagal nerve stimulation by the NCP system, all-cause mortality, and sudden, unexpected, unexplained death.

This report concerns the 2-year extension of the study of mortality and sudden, unexpected, unexplained death in epilepsy (SUDEP) in the cohort of patients receiving vagal nerve stimulation by the NCP System for the treatment of epilepsy. A cohort of 1,819 individuals was followed 3,176.3 person-years from implantation. The 25 deaths that occurred during NCP System activation were reviewed for SUDEP by a panel. The mortality rates were lower [standardized mortality ratio (SMR = 3.6)] with the extended follow-up compared to the previous finding (SMR = 5.3). The SUDEP rates (4.1 vs. 4.5 per 1,000 person-years) were similar to those in the previous study of this cohort. When the vagal nerve stimulation experience is stratified by duration of use, the rate of SUDEP was 5.5 per 1,000 over the first 2 years, but only 1.7 per 1,000 thereafter. The mortality and SUDEP rates are similar to those reported from clinical trials of new drugs and cohorts of severe epilepsy. The lower SUDEP rates after 2 years of follow-up are intriguing, but require further investigation.

Drug interactions with tobacco smoking. An update.

Cigarette smoking remains highly prevalent in most countries. It can affect drug therapy by both pharmacokinetic and pharmacodynamic mechanisms. Enzymes induced by tobacco smoking may also increase the risk of cancer by enhancing the metabolic activation of carcinogens. Polycyclic aromatic hydrocarbons in tobacco smoke are believed to be responsible for the induction of cytochrome P450 (CYP) 1A1, CYP1A2 and possibly CYP2E1, CYP1A1 is primarily an extrahepatic enzyme found in lung and placenta. There are genetic polymorphisms in the inducibility of CYP1A1, with some evidence that high inducibility is more common in patients with lung cancer. CYP1A2 is a hepatic enzyme responsible for the metabolism of a number of drugs and activation of some procarcinogens. Caffeine demethylation, using blood clearance or urine metabolite data, has been used as an in vivo marker of CYP1A2 activity, clearly demonstrating an effect of cigarette smoking, CYP2E1 metabolises a number of drugs as well as activating some carcinogens. Our laboratory has found in an intraindividual study that cigarette smoking significantly enhances CYP2E1 activity as measured by the clearance of chlorzoxazone. In animal studies, nicotine induces the activity of several enzymes, including CYP2E1, CYP2A1/2A2 and CYP2B1/2B2, in the brain, but whether this effect is clinically significant is unknown. Similarly, although inhibitory effects of the smoke constituents carbon monoxide and cadmium on CYP enzymes have been observed in vitro and in animal studies, the relevance of this inhibition to humans has not yet been established. The mechanism involved in most interactions between cigarette smoking and drugs involves the induction of metabolism. Drugs for which induced metabolism because of cigarette smoking may have clinical consequence include theophylline, caffeine, tacrine, imipramine, haloperidol, pentazocine, propranolol, flecainide and estradiol. Cigarette smoking results in faster clearance of heparin, possibly related to smoking-related activation of thrombosis with enhanced heparin binding to antithrombin III. Cutaneous vasoconstriction by nicotine may slow the rate of insulin absorption after subcutaneous administration. Pharmacodynamic interactions have also been described. Cigarette smoking is associated with a lesser magnitude of blood pressure and heart rate lowering during treatment with beta-blockers, less sedation from benzodiazepines and less analgesia from some opioids, most likely reflecting the effects of the stimulant actions of nicotine. The impact of cigarette smoking needs to be considered in planning and assessing responses to drug therapy. Cigarette smoking should be specifically studied in clinical trials of new drugs.

Vitamania: Vitamins in American Culture (review)

Reviewed by: Vitamania: Vitamins in American Culture * Mary Bogin (bio) Vitamania: Vitamins in American Culture. By Rima Apple. New Brunswick, N.J.: Rutgers University Press, 1996. Pp. xi+245; illustrations, notes, index. $48 (hardcover); $18.95 (paper). Vitamania is a well-documented chronicle of America’s enthusiastic embrace of vitamin supplements, first marketed as tablets in the 1920s. Rima Apple begins with the promotional campaigns for cod liver oil in the 1910s and ends with an analysis of why 43 percent of American adults daily ingested vitamin supplements at a cost of more than one billion dollars in 1993. Her well-written social history of vitamin supplements illuminates the question of how Americans make their own interpretations of scientific findings when exposed to a cacophony of information in the form of advertisements, government pronouncements, physicians’ and pharmacists’ advice, and articles in the popular media. Apple does not explain the technological development of vitamin preparations and food fortification or review the scientific research on vitamins. Nor does she try to determine whether vitamin supplements are necessary for optimal health. Instead Apple explores how Americans perceive the adequacy of their diet and the need to supplement it with vitamins. “In the face of fierce disagreement among scientists, . . . why has the American consumer’s love affair with vitamins continued unabated for nearly a century?” [End Page 804] Apple asks (p. 1). Her book provides a useful overview of the history of drug regulation in the twentieth century, from the Food and Drug Act of 1906 to the rigorous clinical trials for new drugs required under the Kefauver-Harris Amendment of 1966. Despite conflicting scientific interpretations of the efficacy of vitamin supplements (except in cases of gross vitamin deficiencies such as rickets and beriberi) and continuing opposition from the American Medical Association and the Food and Drug Administration (FDA), the percentage of Americans consuming vitamins has increased. Apple carefully lays out the arguments of the many sides in the controversy, including those of pharmacists, the vitamin industry, government regulators, members of Congress, organic farming advocates, the grocery industry, Ralph Nader watchdog groups, and consumers. She offers rich documentation from trade journals, court cases, internal memos from vitamin manufacturers, congressional hearings, the FDA archives, advertisements, the popular press, and popular books such as Linus Pauling’s Vitamin C and the Common Cold (1970). Particularly gripping are Apple’s last four chapters on the FDA’s repeated attempts between 1940 and 1994 to regulate the vitamin industry in order to protect consumers from fraudulent claims by vitamin producers. In four major campaigns, the FDA tried to control the selling of vitamins by requiring manufacturers to prove their dietary claims for supplements. In 1973 the FDA proposed new rules that would have divided vitamin products into three categories based on potency, with higher-potency vitamins being classified as drugs, subject to strict clinical trials to prove efficacy. Fearing that the ultimate aim of the FDA was to take supplements off the market or make them available only by prescription, pharmaceutical companies and consumers mounted a fierce defense of the right to take vitamins of any potency in any combination. The volume of mail from consumers to the FDA and members of Congress reportedly was rivaled only by the number of letters received on the Vietnam War and Watergate. Apple shows that consumers resented the paternalism of the proposed FDA regulations and opposed government interference in their freedom of choice to take vitamins. In response to the objections, Congress passed two laws, one in 1976 and one in 1994, to prevent stricter FDA rules and to allow consumers free access to vitamin supplements. Much of the book is an analysis of the aggressive advertising and industrial marketing strategies of vitamin manufacturers. Apple charts the history of how vitamin therapy was sold to middle-class Americans in advertisements that often posed as factual scientific information. For example, Miles Laboratories, the manufacturers of One-A-Day and Flintstones children’s vitamins, implanted the idea between 1945 and 1970 that even Americans with a well-balanced diet needed vitamins to correct insidious nutritional deficiencies that lurked subclinically. Miles characterized vitamins as “nutritional insurance.” [End Page 805] Apple concludes, however, that advertising...

The right to a fair trial

Few newspaper readers can even have been aware of the need for double-blind clinical trials of new drugs, until the recent furore over the early results of such a trial.The Independent was explicit in its front page lead story on 7 April (“Drug can halve the risk of breast cancer”). The Guardian was more cautious (“Drug may halve risk of breast cancer”). Their common subject was the release of data from a trial in the US indicating that tamoxifen might be highly beneficial in women who were especially vulnerable to the disease.The contrast between these and other substantial reports in UK broadsheet newspapers and those in the tabloids was striking. The Sun, for example, ignored the news altogether, while the Mirror gave it three sentences at the bottom of page 7. So much for the women readers of these mass circulation papers.But this was no ordinary clinical trial. The US National Cancer Institute had indeed announced results (from the National Surgical Adjuvant Breast and Bowel Project) which apparently showed a 45% reduction in the risk of invasive breast cancer in those of 13,000 women who had been receiving tamoxifen as a preventative in a double-blind trial.The findings, however, were publicised 14 months before the original target date because early results suggested that the drug was proving highly effective. Abandoning the trial protocol, and thus sacrificing some of the intended clarity in the results, the organizers had taken the unusual step of breaking the double-blind.Hence the prudence of the Guardian's headline, and the cautionary comments from UK experts embedded in its account and in most other UK coverage. In general, however, journalists paid more attention to the known side-effects of tamoxifen, rather than to the possibility that its administration had simply postponed the development of breast cancer and had not prevented it altogether.It was the potential for toxicity, too, which persuaded several US newspapers to use headlines such as “Cancer breakthrough comes with big risk” (USA Today) and “Breast cancer study offers hope but no easy answers” (Los Angeles Times). Although most British accounts mentioned other on-going UK and international studies (albeit briefly in some cases), most US writers totally ignored them.The US papers reflected anxieties about the side-effects, not the incompleteness of the resultsThey continued to do so even after a press conference called in London by the Cancer Research Campaign and the Imperial Cancer Research Fund, which received extensive coverage in the British press on 8 April. In contrast to expert comments published the previous day (“This is very, very encouraging”, Dr Trevor Powles; “We are delighted”, Dr John Toy), the tone became extremely sceptical.“Doctors accuse US of wrecking cancer drug test … Researchers are angry that early announcement of results ruins other trials,” said the results ruins other trails,” said the Times. “US breast cancer claims denounced … It will take years to be sure about new drug,” said the Guardian.The Guardian's coverage at this stage was superb. In addition to a news item, health correspondent Sarah Boseley contributed a comprehensive analysis, two thirds of a page in length, accompanied by diagrams and references to source material. This was a model feature of the type often required by the public but seldom provided by the media, and which is essential to explain such a complex issue fully.The Times adopted a similar approach, with a collation of four pieces on different aspects of the story. One was an admirably succinct summary by science editor Nigel Hawkes of the problems created by the premature termination of the US study, focusing particularly on the important questions that will now never be answered.With the conspicuous exception of the New York Times, caveats concerning the “wrecked” trial were largely absent from US coverage. Reports were tempered, certainly, by warnings of side-effects, and in some instances by careful observations on the potential application of genetic tests to identify high-risk women. But few reporters highlighted the inherent uncertainties in conclusions from a study abandoned long before the end of the time originally deemed necessary for unambiguous results. And the word “breakthrough” was much used.Were UK readers, on the other hand, likely to be confused by the spectacle of one seemingly authoritative group of experts repudiating research findings reported by another? After all, this was not a clash of opinion as to what causes obesity, autism or depression, but a disagreement over the very foundations of scientific method.The question is valid. Nevertheless, Britain's newspaper readers probably learned more about the theoretical and practical dilemma inherent in double-blind studies than US readers did from their country's style of reportage. As the Los Angeles Times observed, this was a story with no easy answers. Yet the wider perspective adopted by most UK journalists did much to aid understanding.

FDA Gets Feedback on Informed Consent Waiver

ABSTRACT LAST SEPTEMBER, the Food and Drug Administration (FDA) invited comment on a new proposal for exceptions from the requirement for obtaining informed consent of patients when testing new drugs or devices during medical emergencies.Now those responses are in, and while most generally support the proposal, many respondents expressed reservations and suggested changes in its details.The proposal, aimed at facilitating research while at the same time protecting the patients involved, describes how and under what circumstances exceptions from consent for this type of research could be granted when patients are unable to give consent because of their medical condition.The FDA had issued its proposal (JAMA. 1995;274:1184-1185) in light of increasing concerns that strict interpretation of current regulations intended to protect human subjects from research-related risks was jeopardizing certain types of studies—clinical trials of new drugs or devices used in life-threatening situations when the patients are unable to give

Clinical trials to study pain in patients with advanced cancer: practical difficulties

Cancer is a common cause of death in our society and associated pain is prevalent in cancer patients. Despite this, pain is often not treated optimally. Although education (patient and caregiver) might improve the situation, many difficulties remain in carrying out clinical trials of new drugs or therapies in this particular group of patients. Appropriate controlled clinical trials need to be designed to maximise validity (randomised, blinding, quality of collected data, enough evaluable patients, statistical analyses) and effectiveness. Patient numbers are often small, the diseases and mechanisms of pain non-homogenous, and assessment techniques and analgesic requirements (and tolerance) may be variable. Furthermore, pain may be unstable, polypharmacy is often involved, behavioral and other cognitive factors may change, patient compliance may be suspect, and side effect profiles may be difficult to interpret (disease, patient status, polypharmacy). Strategies that may increase validity constrain the feasibility of the study and the generalisability of the study results obtained.

Pharmacokinetic parameters relevant to recovery from opioids.

Several recent studies have suggested that the terminal half-lives of many drugs do not predict the rate of washout of drug after the relatively short durations of infusions used in anesthesia. Many anesthetic drugs fit a three-compartment mamillary model, with three volumes of distribution (central [V1] and peripheral [V2 and V3]) and three clearances (elimination or metabolic [Cl1] and distribution [Cl2 and Cl3]). It has been suggested that a large V3:Cl3 ratio contributes to rapid recovery after infusion. We investigated the role of each of these primary pharmacokinetic parameters to determine values of each that would contribute to rapid recovery after various dosing schemes. Three sets of computer simulations were performed based on a three-compartment mamillary model for fentanyl, alfentanil, and sufentanil. Set I predicted the change in plasma concentration of each drug after a bolus if each pharmacokinetic parameter were independently increased by 5%. Set II predicted the time for an 80%, 50%, or 20% decrease in plasma concentration after infusions of varying duration (the 80%, 50%, and 20% decrement time, respectively) if each pharmacokinetic parameter were independently increased by 5%. Set III calculated the percent change in each pharmacokinetic parameter alone that would give a 30% shorter decrement time after infusions of varying duration. Set I demonstrated that after a bolus dose to obtain identical initial plasma concentrations, the drug with a larger V1 had a higher plasma concentration than did the parent drug at all subsequent times. The drug with a larger Cl1 had a lower plasma concentration than did the parent drug at all times. A larger V2, V3, Cl2, or Cl3 led to a lower plasma concentration at times soon after the bolus and subsequently to a higher plasma concentration than did the parent drug. Set II demonstrated that after an infusion, increasing V1 led to a longer decrement time and increasing Cl1 led to a shorter decrement time for infusions of all durations. Increasing V2, V3, Cl2, or Cl3 led to a shorter decrement time when the infusion had been short and when a small decrease in plasma concentration was desired. Increasing each of these four parameters led to a longer decrement time when the infusion had been long and when a larger decrease in plasma concentration was desired. Set III demonstrated that a smaller V1 or a larger Cl1 always led to a shorter decrement time. For infusions of short duration and for a small decrease in plasma concentration, a larger V2, V3, Cl2, or Cl3 led to the desired decrease in decrement time. For infusions of longer duration and for larger decreases in plasma concentration, a smaller V2, V3, Cl2, or Cl3 was able to decrease the decrement time by 30%. This study proposes qualitative guidelines for pharmacokinetic properties desirable in anesthetic drugs. If a rapid decrease in plasma concentration is desired after an infusion, it is always beneficial to have a small V1 and a large Cl1. For infusions of short duration, after which only a small decrease in plasma concentration is required, it is beneficial to have a larger V2, V3, Cl2, and Cl3. For infusions of longer duration, after which a large decrease in plasma concentration is desired, it is beneficial to have a smaller V2, V3, Cl2, and Cl3. These proposals may be beneficial for planning clinical trials of new drugs.

Women in clinical trials of new drugs. A change in Food and Drug Administration policy. The Working Group on Women in Clinical Trials.

The Food and Drug Administration (FDA) is taking two important steps to ensure that new drugs are properly evaluated in women. First, it is providing formal guidance to drug developers to emphasize its expectations that women will be appropriately represented in clinical studies and that new drug applications will include analyses capable of identifying potential differences in drug actions or efficacy between the sexes. Second, the agency is altering a 16-year-old policy that has excluded most women with “childbearing potential” from the earliest phases of clinical trials. Attention to sex differences is part of a larger effort by the FDA . . .

Some FDA perspectives on data monitoring in clinical trials in drug development

The FDA's interest in data monitoring of clinical trials derives from its public health responsibility to assure the safety and efficacy of new drugs based on evidence from adequate and well-controlled studies. Therefore the FDA is concerned that clinical trials of new drugs are designed and carried out in a manner that will insure the integrity and validity of study inferences. The FDA regulation and guidelines recognize the role of data monitoring and the variety and diversity of situations utilizing a data monitoring process in clinical studies. This paper describes relevant aspects of the regulations and guidelines, some concerns the FDA has with regard to monitoring of both government- and industry-sponsored trials and the consequences of early termination of trials of new drugs in the investigational and marketed stages. Comments include advice on communication between the FDA and data monitoring committees.

Position Paper: A Women's Health Research Agenda

Journal of Women's HealthVol. 2, No. 2 Position Paper: A Women's Health Research AgendaTRACY L. JOHNSONTRACY L. JOHNSONSearch for more papers by this authorPublished Online:12 Jun 2009https://doi.org/10.1089/jwh.1993.2.95AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByCultural and Spiritual Meanings of Childbirth24 June 2016 | Journal of Holistic Nursing, Vol. 17, No. 3Gay Male, Lesbian and Bisexual Health-Related Research Funded by the National Institutes of Health Between 1974 and 1992Journal of Homosexuality, Vol. 37, No. 1Cultural Meanings of Childbirth24 June 2016 | Journal of Holistic Nursing, Vol. 15, No. 4Reframing women's health in nursing education: A feminist approachNursing Outlook, Vol. 43, No. 6Women’s Health: Nurses Pave the WayJournal of Obstetric, Gynecologic & Neonatal Nursing, Vol. 24, No. 3Gender Equity in Research12 June 2009 | Journal of Women's Health, Vol. 3, No. 3Women and the Family of the FutureJournal of Obstetric, Gynecologic & Neonatal Nursing, Vol. 23, No. 2Women in Clinical Trials of New Drugs -- A Change in Food and Drug Administration PolicyNew England Journal of Medicine, Vol. 329, No. 4 Volume 2Issue 2Jan 1993 To cite this article:TRACY L. JOHNSON.Position Paper: A Women's Health Research Agenda.Journal of Women's Health.Jan 1993.95-98.http://doi.org/10.1089/jwh.1993.2.95Published in Volume: 2 Issue 2: June 12, 2009PDF download

Coccidioidomycosis: changes in clinical expression, serological diagnosis, and therapeutic options.

Coccidioidomycosis occurs in greater than 50,000 persons each year. As concurrent infections with the human immunodeficiency virus become more frequent, the spectrum of coccidioidal illness has shifted toward more extensive and life-threatening disease. This trend has intensified interest in developing more-sensitive methods for diagnosis of coccidioidal infection early in its course. ELISA procedures that detect fungal antigen and antibodies in patient sera have been devised but require more-purified antigens for clinically useful specificity. Clinical trials of new drugs have been initiated that may offer advantages in safety, efficacy, or ease of administration. Itraconazole and fluconazole show promise, especially in the treatment of coccidioidal meningitis. However, it has not yet been determined whether either antifungal agent is more effective than established agents, such as amphotericin B or ketoconazole. These changes in the clinical spectrum, methods of diagnosis, and therapeutic options will likely influence the medical approach to coccidioidal infections in coming years.

Good Clinical Practices in the US: Impact of European Guidelines

The Food and Drug Administration (FDA) must be assured that the clinical trials of new drugs are properly conducted, that the data are accurately reported, and that the risks to the subjects are minimized, regardless of whether the studies are performed in the United States or in foreign countries. The FDA's standards for conducting clinical trials are set forth in the Investigational New Drug regulations, the Protection of Human Subjects regulations, and the Institutional Review Board (IRB) regulations. The FDA has also prepared monitoring guidelines for sponsors, and numerous other guidelines for clinical investigators and institutional review boards. Regulations, guidelines, and the criteria for the acceptance of foreign drug studies are reviewed. An overview of foreign clinical inspections is presented and the perceived impact of the European Community (EC) Good Clinical Practices requirements is discussed.

The analysis of failure time data in crossover studies

Clinical trials of new drugs in the treatment of angina pectoris frequently make use of exercise tests to evaluate efficacy. The crossover design is often employed. The methods commonly used to analyse the various exercise times, for example, 'time to pain', are insensitive and potentially biased by the manner in which they deal with the censored nature of the data. Survival analysis can be adapted for use in crossover trials, both in a relatively simple way, and also through the full power of the Cox model. This is considerably more sensitive and not subject to the same bias. This methodology leads to the use of median survival times to illustrate treatment effects and this provides a practical interpretation of clinical relevance. The estimation of median survival times in crossover trials poses some special problems. The methodology is illustrated throughout by means of a specific two-period example in which atenolol was compared with the combination of atenolol and nifedipine. The three-period design is also briefly discussed.

Evaluating results of clinical trials in treatment of complicated urinary tract infection

Clinical trials of new drugs should produce results that are not due to chance, inherent differences in groups, or handling of the groups by the investigator. These sources of error may be prevented by having groups of a size that provides sufficient statistical power and thus rules out sample variation. Differences in groups can be prevented by randomization, and double blinding the subjects prevents investigator bias.