Efficacy data

Safety and efficacy data on a number of antitussives and expectorants have been reviewed by the FDA s Advisory Review Panel on Over-the-Counter (OTC) Cough, Cold, Allergy, Bronchodilator, and Antiasthmatic Products. The conclusions and recommendations regarding the effectiveness, safety, labeling, and suitability for marketing of over-the-counter preparations have been reported (103). After review of these recommendations, FDA has issued final monographs for over-the-counter antitussives (12) and for expectorants (1). LD q data for most of the compounds described have been reported (104,105). 

Safety and quality aspects are the main topics that must be addressed from a regulatory perspective at the pre-clinical phase of drug development. Indicative efficacy data will also be obtained, but authoritative data can be obtained only from clinical studies conducted with humans. Safety and preliminary efficacy indications... 

Samples of blood and excreta are taken for laboratory analysis. It is expected that, at the end of this phase, you will have a preliminary estimate of the maximum dose that may be safely tolerated in humans, and also a basic profile of the drug s pharmacokinetic behaviour. Depending on the availability of appropriate analytical indicators, pharmacodynamic and indicative efficacy data may also be generated. The data acquired must be carefully analysed and assessed so that, based on the findings, appropriate Phase II trials can be planned. 

Generic Application (based on reference product Safety and Efficacy data)... 

The developer may receive conditional approval for up to five years, through annual renewals, on the basis that the safety has been established, but that complete efficacy data will only be generated during the conditional approval period. The labelling must bear the statement conditionally approved by FDA pending a full demonstration of effectiveness under application number . 

The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy, in which case additional safety and efficacy data are required. The same qualitative and quantitative composition only applies to the active ingredients. Differences in excipients will be accepted unless there is concern that they may substantially alter the safety or efficacy. The same pharmaceutical form must take into account both the form in which it is presented and the form in which it is administered. Various immediate-release oral forms, which would include tablets, capsules, oral solutions and suspensions, shall be considered the same pharmaceutical form for this purpose. 

The EU will accept applications without supporting pre-clinical and clinical data, if it can be demonstrated that the active substances have been in well-established medical use in the Community for at least 10 years, with recognised efficacy and an acceptable level of safety. This route would be appropriate for many common over-the-counter (OTC) products. Safety and efficacy is supported by providing copies of published scientific literature as part of the submission that is, the submission relies on safety and efficacy data available in the public domain, as opposed to confidential data from authorised applications that is the cornerstone of generic applications. 

An EU application for a combination product that contains previously authorised active substances must be supported by appropriate safety and efficacy data for the combination. However, there is no need to submit data on the safety and efficacy of the components individually. The combination product is considered a unique product distinct from the authorisations granted to the individual ingredients, and will thus have a separate exclusivity clock running from the date when the combination was authorised. 

The most advanced PDF inhibitor to emerge thus far from this collaboration is LBM-415 (12) (also called NVP PDF-713 or VIC-104959), an V-formyl-V-hydroxylamine compound still containing a proline residue at P2. The activity, PK properties, and in vivo efficacy data of (12) were presented at the 14th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) (2004) and the structure of this... 

Acupressure and acupuncture have been investigated based on the theory that certain points on the body control specific bodily functions.11 The P6 (Neiguan) point on the inside of the wrist has been used historically by acupuncturists to treat nausea and vomiting. While this approach seems safe and cost effective, efficacy data in the treatment of NVP are conflicting. The majority of studies showed a benefit to this approach, but the studies had methodologic flaws.9,11,12... 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

MPA derivatives have replaced azathioprine as the antiproliferative agent of choice in most organ transplant centers. The MPA derivatives generally are considered to provide a more specific immunosuppressive effect compared with azathioprine. Mycophenolate mofetil and enteric-coated mycophe-nolic acid have similar safety and efficacy data in renal transplant recipients. 

In addition to relying on safety and efficacy data, the initial DMARD choice depends on disease severity, patient characteristics (i.e., comorbidities, likelihood of adherence), cost, and clinician experience with the medication.1,7 Methotrexate alone or in combination therapy is the initial treatment of choice for patients with aggressive disease. Patients with early, mild disease may receive monotherapy with sulfasalazine or hydroxychloroquine. Agents such as azathioprine, D-penicillamine, and gold salts are used rarely today because of concerns about toxicity and reduced efficacy.1,15... 

The newer quinolones have a greater spectrum of activity. These agents are effective for pyelonephritis. Avoid in pregnancy and children. Moxifloxacin is not listed due to lack of indication and efficacy data. 

The reason for this confusing situation is that all efficacy data are depending from the test method used to find the effective time - concentration ratio of the disinfectant. 

There are different ways to classify clinical trial data. As mentioned earlier, data can be classified by their physical nature into discrete chunks or as a more continuous measurable quantity. In clinical trials there are other important contextual ways of grouping data as well. For instance, clinical trials are primarily focused on determining two things about a drug, biologic, or device Is it efficacious, and is it safe The data that help to answer these questions are broadly classified as efficacy data and safety data, respectively. 

In this form, event would be replaced by some clinical finding such as myocardial infarction, stroke, seizure, or the like. This example form is extremely simplified, as there are usually a number of associated data variables captured as well. The event/endpoint page data must be clean, because it likely captures the primary efficacy data for the clinical trial. 

Where antioxidants or antimicrobial preservatives are used, the finished product release specification will need to include identification tests and assays for these two types of excipient. The shelf life specification should also include a specification for assay for antimicrobial preservatives. Stability data will be required for both antioxidants and antimicrobial preservatives in the finished product, and in addition the preservative efficacy of the formulated product should be examined over its shelf life and by means of appropriate in-use stability tests. Preservative efficacy data should also be presented at the lower limit of the preservative assay. 

A metaanalysis indicated that EGb 761 (an extract of ginkgo biloba) may have some therapeutic effect at doses of 120 to 240 mg of the standard leaf extract twice daily. Because of limited efficacy data, the potential for adverse effects (e.g., nausea, vomiting, diarrhea, headache, dizziness, weakness, and hemorrhage), and the poor standardization of herbal products, it is recommended that ginkgo biloba be used only with caution. 

Diazepam may be used (5 mg three times daily), but efficacy data are conflicting. 

Recently, a Japanese research group published preclinical safety and efficacy data of an oral antiestrogen (TZE-5323) (Saito et al. 2003). This drug has been shown to have a strong affinity for human ERa and ER/i and a dose-dependent capacity to inhibit estradiol-stimulated transcriptional activation (Saito et al. 2003). In the experimental endometriosis model in rats, TZE-5323 dose-dependently reduced the volume of the endometrial implant with an effectiveness similar to that of danazol and leuprorelin acetate without causing significant changes in bone mineral density and in serum estradiol levels (Saito et al. 2003). 

A number of other small molecule Syk kinase inhibitors have been reported in the literature [61-64], Since there are no reports of detailed evaluation or animal efficacy data, some of these inhibitors may not have advanced further. 

How Will Conducting a Clinical Trial in a Pharmacogenetically Defined Subset of Patients Influence the Collection of Adequate Safety and Efficacy Data Prior to Registration ... 

The time between immxmizing the mice with CD20 (August 1990) and filing the IND for Rituxan (December 1992) was 2 years and 4 months. That brief span encompassed the first time IDEC had ever produced and manufactured a recombinant antibody in CHO cells for clinical trials in humans. The IND also included safety and efficacy data in primates, in which monkeys who had had their normal B cells completely depleted from their blood and depleted in part from their lymph nodes showed no adverse events. In addition, a human y4 version of rituximab was shown not to deplete B cells in monkeys, indicating for the first time that the Fc portion of the human yl antibody was contributing to depletion of cells with CD20 on their surface in vivo ... 

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