Drug Evaluation Committee Research Articles

Gender and racialisation of pharmaceutical sector leaders in Canada: a cross-sectional study

Objective/designLacking diversity in pharmaceutical leadership positions could contribute to inequities in medicine access. The objective of this cross-sectional study was to determine the gender and racial identities of individuals who...

Fetal Exposure to Risky Drugs: Analysis of Antenatal Clinic Prescriptions in a Nigerian Tertiary Care Hospital

Objective: To assess fetal outcomes after in-utero exposure to unsafe drugs.Methods: This was a retrospective cohort study using data from medical records of pregnant women who received antenatal care over a two-year period (2019/2020). Inclusion was based on identification of prescription of potentially risky medications during pregnancy. Medication records, as well as delivery data, were extracted for analysis. The Australian drug evaluation committee classification system of risky medications was used for analysis.Results: Results showed that 44 – 65% of medicines prescribed in pregnancy carry significant risks to fetal wellbeing. Fetal outcomes showed high levels of low birth weight, still birth, and early neonatal death. The common medicines prescribed irrationally in pregnancy were, among others, antibiotics, ACEIs, NSAIDs, Biguanides, and opiates, all of which are associated with adverse fetal outcomes.Conclusion: There is a high level of fetal exposure to risky medications and adverse delivery outcomes. There is a need to improve prescription through prescriber training and awareness raising on existing guidelines on good prescribing practice for pregnant women.

Pioneers in Dermatology and Venereology: an interview with Professor Xue-Jun Zhu.

Member of National Pharmacopoeia committee Member of Drug Evaluation Committee, State Food and Drug Administration Member of National Committee for National Natural Scientific Foundation International honorary member, American Dermatological Association International honorary member, Germany Dermatological Association My father was a dermatologist trained in St. Louis Hospital in Paris, France, in the 1930s. He was the one who led me to the Dermatology field. Hu C.K.M.D.; he was a great dermatologist in China and the first scholar who described vitamin D deficiency in the world. He introduced me to the immunology. Wang K.C.M.D.; former chairman of my department. He guided me on how to be a good clinical dermatologist. Rudolf L. Baer; he was a great dermatologist as well as a great organizer. I learnt how to run a department and how to organize a group of outstanding scholars working together. A. Bernard Ackerman; he was a great dermatopathologist and I learnt how to be a good speaker from him. Jean-Claude Bystryn and Irma Gigli; they taught me a lot on how to think and how to do research work. Yes. See above in “Academic engagements” in detail. Firstly, I discovered the pathogenic mechanism of paraneoplastic pemphigus (PNP) which suggested early detection of the associated tumour and early resection. Then, this resulted in a great reduction of the mortality of PNP. Secondly, I established the China Dermatologist Association as one of the initiator and promoters and contributed in the development of dermatology in China. I lost more than 10 years (1965–1975) because of the ‘culture revolution’ in my country. Classical music and travelling. Composers: Beethoven, Chopin, Tchaikovsky, Rachmaninoff. Writer: Jean L. Bolognia; Arthur Conan Doyle. Steve Katz, Otto Braun-Falco, Rudolf L. Baer, A. Bernard Ackerman, Walter F. Lever, Albert M. Kligman, Richard K. Winkelmann, Stefania Jablońska, Chuan-kuei Hu, Darrell Wilkinson. June K. Robinson, Bruce Wintroub, Timothy Berger, Jouni Uitto, John R. Stanley, Jean Paul Ortonne, Takaji Nishikawa, Thomas Luger, Zhou Bian, Georg Stingl. Ethical aspects of gene therapy. Also, more and more biological therapy will be emerging in the market, however, will be too expensive to be used worldwide. Targeted therapy; gene therapy. *Note: The Pioneers in Dermatology and Venereology interview was conceived and conducted by Johannes Ring.

Unexpected in utero exposure to psychotropic medications

Introduction Pregnancies in the world each year involve women who have or who will develop psychiatric illness during the pregnancy. Psychotropics in gestation could produce adverse perinatal and postnatal outcomes, however counseling these women to discontinue medication presents new risks associated with untreated or inadequately treated mental illness, such as poor prenatal care, inadequate nutrition, and increased alcohol and tobacco use. The single administration at a higher dosage over multiple medications, active pharmaceutical compounds with fewer metabolites and higher protein binding are preferred. Nevertheless all psychotropic medications cross the placenta, are present in amniotic fluid, and can enter breast milk. Case description The FDA, the Australian Drug Evaluation Committee and Micromedex have categorized medications according to risk during pregnancy. Based on these classifications Benzodiazepines, have been demonstrated possibly teratogenic however they are still used for treating anxiety, panic, seizures and insomnia. International Pharmacopoeia reported an increased risk of intrauterine growth retardation, hypotonia, bradycardia, respiratory depression, low Apgar and preterm delivery for fetal plasma drug concentrations equivalent to the therapeutic range of maternal prescription. Very few data are published on sudden intrauterine death (SIUD) for intrauterine exposure to psychotropic medication. We describe a SIUD correlated with unexpected toxic plasmatic fetal concentration of Lorazepam. Results and conclusions The pregnant manifested anxiety, panic attack and deficiency of emotional transport for the fetus. She was treated with Lorazepam evening dose of 2mg from 24 to 40 gestational weeks, according to therapeutic range prescription, when suddenly and unexpectedly fetus died in utero just before the delivery. We evaluated the maternal and fetal pharmacological plasmatic concentration and observed a fetal plasmatic level of Lorazepam of 330mcg/l greater the toxic cutoff of 45mcg/l, suggested by Micromedex to cause floppy infant syndrome. By autoptic diagnosis we hypothesized neuropathological signs of sudden cardiac arrest in health fetus. Take-home message We propose that the monitoring of the maternal plasma levels of benzodiazepines during pregnancy and assessment of the concentration umbilical cord at birth, have to be correlated with the fetal vital signs. Nevertheless, it is difficult to define the metabolic fate of drugs in utero. Each of the major metabolic pathways can be promoted by placental and/or fetal enzymes and the metabolite concentration in the fetus does not ineludibly reflect the ability of the fetus to metabolize drugs. For this reason it has to be strictly evaluated the toxicological etiopathogenesis of some cases of SIUD and still birth.

Regulatory Forum Opinion Piece*: Transgenic/Alternative Carcinogenicity Assays: A Retrospective Review of Studies Submitted to CDER/FDA 1997-2014.

The International Conference on Harmonization (ICH; S1B of 1997) allows a second species carcinogenicity study to be an alternative to one of the traditional 2-year studies. In the past 17 years, the FDA's Center for Drug Evaluation and Research's (CDER) Executive Carcinogenicity Assessment Committee received 269 alternative carcinogenicity assay protocols for review. This committee's recommendations regarding choice of animal model and dose selection are generally followed by sponsors conducting these studies to increase the acceptability of such studies. The P53(+/-) assay is generally considered appropriate for genotoxic products, and the TgRasH2 assay is appropriate for non-genotoxic or genotoxic drugs. In the United States, the TgAC assay is not used any more and the animals are no longer available. The TgAC assay can detect both tumor promoters and complete carcinogens, and consequently more than half of the dermal TgAC assays resulted in a positive assessment. Currently, more than 75% of mouse carcinogenicity studies are conducted in TgRasH2 mice. Behavior of genotoxic and non-genotoxic drugs in the various assays is reviewed.

Revisiting financial conflicts of interest in FDA advisory committees.

The Food and Drug Administration (FDA) Safety and Innovation Act has recently relaxed conflict-of-interest rules for FDA advisory committee members, but concerns remain about the influence of members' financial relationships on the FDA's drug approval process. Using a large newly available data set, this study carefully examined the relationship between the financial interests of FDA Center for Drug Evaluation and Research (CDER) advisory committee members and whether members voted in a way favorable to these interests. The study used a data set of voting behavior and reported financial interests of 1,379 FDA advisory committee members who voted in CDER committee meetings that were convened during the 15-year period of 1997-2011. Data on 1,168 questions and 15,739 question-votes from 379 meetings were used in the analyses. Multivariable logit models were used to estimate the relationship between committee members' financial interests and their voting behavior. Individuals with financial interests solely in the sponsoring firm were more likely to vote in favor of the sponsor than members with no financial ties (OR = 1.49, p = 0.03). Members with interests in both the sponsoring firm and its competitors were no more likely to vote in favor of the sponsor than those with no financial ties to any potentially affected firm (OR = 1.16, p = 0.48). Members who served on advisory boards solely for the sponsor were significantly more likely to vote in favor of the sponsor (OR = 4.97, p = 0.005). There appears to be a pro-sponsor voting bias among advisory committee members who have exclusive financial relationships with the sponsoring firm but not among members who have nonexclusive financial relationships (ie, those with ties to both the sponsor and its competitors). These findings point to important heterogeneities in financial ties and suggest that policymakers will need to be nuanced in their management of financial relationships of FDA advisory committee members.

La Haute autorité de Santé (HAS)

The French National Authority for Health (Haute Autorité de Santé, HAS) was created in 2004. The aim of this study was to examine three of its principal responsibilities, namely certification of healthcare facilities, definition of chronic illnesses (ALD, affections de longue durée), and production of clinical practice guidelines. The authors did not assess other HAS responsibilities, such as the role of the drug evaluation and reimbursement committee (Commission de Transparence). Healthcare facility certification cost at least 22.4 million € in 2012 and involved 89 HAS personnel and 681 external auditors; medical issues were considered from only a very general and theoretical standpoint, leading the national ombudsman (Cour des Comptes) to qualify them as "blind spots". HAS is required to provide only an overall assessment of each healthcare institution, even though different departments may be of highly variable quality. Chronic illnesses are somewhat vaguely defined, permitting flexible interpretation by health insurers' medical experts. This leads to considerable disparities from one region to another in the number of patients qualifyingfor this status. Finally, practice guidelines must be more firmlly based on the results of the most rigorous and properly referenced scientific studies, and the resultinzg documents must be written more strictly, clearly and briefly, hi conclusion, HAS performance in the three roles we examined is disappointing Certification of healthcare institutions could be replaced by unannounced inspections by the General Welfare Inspectorate, health insurers, or regional health agencies. The definition of chronic illnesses and the production of practice guidelines could be handed over to scientific societies or academies, as illustrated by the case of hypertension.

Delays in access to affordable medicines: putting policy into perspective

We raise some issues with the study by Pearce et al. that examined the timelines of submissions for medicines to the Pharmaceutical Benefits Advisory Committee (PBAC) following recommendation by the Australian Drug Evaluation Committee (ADEC), now known as the Advisory Committee on Prescription Medicines (ACPM).

Delays in access to affordable medicines: putting policy into perspective

To save costs, the Australian Government recently deferred approval of seven new medicines recommended by the Pharmaceutical Benefits Advisory Committee (PBAC) for up to 7 months. The aim of this research is to examine the timelines of PBAC applications following approval by the Therapeutic Goods Administration (TGA), allowing the recent Cabinet delays to be considered in the context of the overall medicines approval process. All new chemical entities and products for new indications approved in 2004 by the Australian Drug Evaluation Committee (ADEC) were identified. Outcomes of PBAC meetings from 2004 to 2010 were then searched to identify if and when these products were reviewed by PBAC. ADEC recommended 63 eligible products for registration in 2004. Of the 113 submissions made to PBAC for these products, 66 were successful. Only 43% of the products were submitted to PBAC within 2 years, with an average 17-month delay from TGA approval of a product to consideration by the PBAC. Cabinet decisions to defer listing of new medicines delays access to new treatments. This occurred in addition to other longer delays, earlier in the approval process for medicines, resulting in a significant impact on the overall timeliness of listing.

Farklı Risk Kategorilerine Göre Gebelikte İlaca Maruz Kalımın Değerlendirilmesi: FDA Esaslı Kararlar Daha Fazla Küretaja Neden mi Oluyor?

Objective: The aims of the study were to compare the risk levels of exposed drugs during pregnancy with regard to United States Food and Drug Administration (FDA), Australian Drug Evaluation Committee (ADEC) and Teratogen Information System (TERIS) risk categories, and to determine the outcomes of FDA risk category based decisions on the course of pregnancy in pregnant women who applied to Dokuz Eylul University (DEU) Teratogenity Information Service (TIS). Material and Methods: In this cross-sectional study, 220 pregnant women were enrolled who referred to DEU TIS for a teratogenity risk evaluation due to drug exposure during their pregnancies. Demographics, medical history, time and duration of the exposed drugs were recorded. Drugs exposed during pregnancy were divided into two categories as high or low risk. A drug that was exposed during pregnancy of the highest risk according to FDA was taken into consideration for the evaluation of the outcomes of the pregnancy. Additionally, FDA, TERIS and ADEC risk categories which were classified as

MLR–ANN and RTO Approach to μ‐opioid Receptor‐binding Affinity. Pooling Data from Different Sources

One hundred and six morphinan derivatives were taken from the Drug Evaluation Committee reports to propose several quantitative structure-activity relationship models to describe the mu-receptor-binding affinity. After several procedures to reduce the descriptor number, 21 descriptors were selected for the descriptor pool by a complete Multiple Linear Regression methodology. In this procedure only three molecules were considered as outliers. Several tests changing the relation between training:predicted sets were considered to find the best relation between these sets. The higher the number of molecules in the predicted set the higher the predictive power was observed. The optimal number of descriptors was established using the Akaike's information criterion and Kubinyi fitness function parameters. The Artificial Neuron Network methodology was applied to improve the Multiple Linear Regression best result. Finally, the regression through the origin methodology was applied to establish the best model from the Artificial Neuron Network methodology. The best quantitative structure-activity relationship model was proven to be independent of chance correlation.

The Australian Drug Evaluation Committee (ADEC) has recommended approval for lenalidomide

The Australian Drug Evaluation Committee (ADEC) has recommended approval for lenalidomide

QSAR Study on the Antinociceptive Activity of Some Morphinans

Quantitative structure-activity relationship studies were performed to describe and predict the antinociceptive activity of 31 morphinan derivatives reported by the US Drug Evaluation Committee in 2005 and 2006. From these, three data sets were constructed and several models were calculated following the multiple linear regression and Leave-One-Out Cross-Validation (LOO-CV) tests. In general, these models achieved good descriptive power (approximately 92%) as well as predictive power (approximately 76%), but were unable to predict an external validation set of morphinan derivatives. When artificial neural networks were applied to these models, an improvement of the predictive and external validation values was obtained. It was observed that the results of the NN models are significantly better that those obtained by multiple linear regression. In spite that the problem under investigation can be handled adequately by a linear model, a neural network does bring slight improvements in the predictive power.

非臨床安全性研究担当者の教育に関するアンケート調査報告（１）：日本の製薬企業における教育の現状 - 日本製薬工業協会 基礎研究部会 教育タスクフォース -

非臨床安全性研究担当者の教育に関するアンケート調査報告（１）：日本の製薬企業における教育の現状 - 日本製薬工業協会 基礎研究部会 教育タスクフォース -

非臨床安全性研究担当者の教育に関するアンケート調査報告（２）：安全性試験実務者の教育 -日本製薬工業協会 基礎研究部会 教育タスクフォース-

非臨床安全性研究担当者の教育に関するアンケート調査報告（２）：安全性試験実務者の教育 -日本製薬工業協会 基礎研究部会 教育タスクフォース-

非臨床安全性研究担当者の教育に関するアンケート調査報告（３）：総合的安全性評価者の育成 - 日本製薬工業協会 基礎研究部会 教育タスクフォース -

非臨床安全性研究担当者の教育に関するアンケート調査報告（３）：総合的安全性評価者の育成 - 日本製薬工業協会 基礎研究部会 教育タスクフォース -

Case studies of three pregnant smokers and their use of nicotine replacement therapy

To examine the barriers encountered by pregnant women who attempt to stop smoking by highlighting three women who used nicotine patches. A randomised-controlled trial of nicotine-replacement therapy (NRT) in the form of patches to test its acceptability for pregnant women. Ethics approval was granted despite NRT being contraindicated in Australia for pregnant women and having a low safety rating (category D) (Australian Drug Evaluation Committee, 1999). Salivary cotinine levels were used to assess nicotine exposure and provide some indicator of NRT safety. All participants were given pregnancy-specific cessation counselling, and the 20 women in the treatment arm were offered nicotine patches (15 mg/16 hr), with the option of weaning to lower strength patches if desired. The Women's and Children's Hospital, Adelaide, a public tertiary teaching hospital in South Australia, with almost 4000 births annually. 40 'high-risk' pregnant smokers who expressed interest in stopping smoking. As has been found in the general population, 'quit' rates with NRT use were low. Only three of the participants in this study, who became abstinent with patch use during pregnancy, were still abstinent at birth. The circumstances of two of these women, and a third woman who used patches to 'control' her smoking despite researcher advice, are detailed here. Only one of the two women 'abstinent at delivery' was still abstinent 3 months after birth, the last contact point of the study. Although health providers intuitively regard pregnancy as an appropriate time for women to stop smoking, the stressors during pregnancy seem to militate against cessation. This study does not indicate that use of NRT will provide an easier solution. It may be more fruitful to institute a concerted lifestyle approach with both the woman and her partner (or significant household members), and continue this support and education postnatally if cessation has not been achieved. Health professionals should also support better-targeted public health campaigns and tobacco-control initiatives generally, because, undoubtedly, the social environment is a major determinant of initiation and continuation of smoking.

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

Australian Drug Evaluation Committee (ADEC) 40th Anniversary

The 40th anniversary of the Australian Drug Evaluation Committee, commonly known as ADEC, occurred in late July 2003. ADEC first met on Thursday 25 July 1963, under the Chairmanship of Dr Edgar Thomson, in the boardroom at the Royal Prince Alfred Hospital, Sydney. The Committee was composed of seven members eminent in the fields of clinical medicine and pharmacology. ADEC has met regularly since and its August 2003 meeting was its 229th meeting. Australia was centrally involved in the recognition of the teratogenicity of thalidomide. William McBride’s letter published in the Lancet in December 1961 attracted the world’s attention. In 1963, to a large extent as a result of the thalidomide experience, discussions took place between the Australian Department of Health and senior Australian clinicians on ways and means of more effectively exerting control over drugs causing serious adverse effects. The thalidomide experience had brought home to Australian health officials that there were not only benefits but also potential risks from the use of therapeutic compounds. As a result of these discussions, the then Minister for Health established an independent body, the ADEC, to advise on the safety of new drugs being imported into Australia and to formulate measures for the evaluation of possible adverse affects of drugs that were being used in Australia. The functions given to the new Committee were: • to make medical and scientific evaluations of such therapeutic substances that the Minister referred to it for evaluation; • to make medical and scientific evaluations of other therapeutic substances if, in the opinion of the Committee, it would be desirable to do so; and • to furnish such advice to the Minister as the Committee considered necessary related to the importation into, and the distribution within, Australia of therapeutic substances that were the subject of evaluations made by it. ADEC met three times during 1963. These meetings laid the foundations for what would become the evaluation process for new drug substances in Australia. General topics discussed at these early meetings included the functions of the ADEC, the definition of a new drug, details of the future Australian drug evaluation process using comparisons with international practice at the time and the role of the individual medical practitioner in drug safety surveillance. Standards for submission of data for importation of medicines into Australia were introduced as a result of the early recommendations of the Committee. The Committee also sought to ensure that companies were required to provide information about risks, as well as benefits, in promotional material for health professionals. The early ADEC made a number of important decisions in relation to individual product groups. Drug substances discussed by the Committee in 1963 included Enovid® 1, the first oral contraceptive approved by the US FDA, which was of great interest to the pharmaceutical industry at the time. In the wake of thalidomide, any drug with such widespread potential use in women of childbearing years encountered a rather cautious regulatory environment. ADEC advised of the need for medical supervision of patients using oral contraceptives. Interestingly, ADEC was not convinced of a cause and effect relationship between use of oral contraceptives and thrombosis at that time. It was 3 or 4 years later before studies in Europe showed convincingly the link between high-dose oestrogens and thrombotic events. The early ADEC also acted to discourage the use of some long-acting sulphonamides, which were widely used in general practice at the time. These sulphonamides were causing StevensJohnson syndrome, especially in children. There had been 19 cases reported in Australia, mainly in children, with four deaths. In 1964, ADEC undertook a detailed review of five Australian reports to it of deaths in patients using sympathomimetic drugs to treat severe asthma. Subsequently, the Committee published a warning in the January 1965 issue of the Medical Journal of Australia. This warning was an important stimulus to studies in the UK and elsewhere of the association between pressurised

The Australian Drug Evaluation Committee has recommended for approval Pharmion's thalidomide

The Australian Drug Evaluation Committee has recommended for approval Pharmion's thalidomide