Efficacy and Safety

The most commonly reported adverse events of moderate or severe intensity that occurred in 2% of patients treated with raltegravir were headache, nausea, asthenia/weakness, and fatigue. It is interesting that the STARTMRK study showed that patients on raltegravir-based combination treatment showed significantly less impact on lipid levels than patients on efavirenz-based combination treatment.32 33 

In the initial clinical study with DCV, which represented a proof-of-concept trial for the HCV NS5A inhibitor mechanism, GT-1 HCV-infected subjects were administered single doses of 1,10, and 100 mg of the drug, and plasma viral load was followed for 7 days. A reduction in viremia that was both rapid and profound was observed at all doses, with mean declines in viral load of 1.8, 3.2, and 3.3 logio at the 1, 10, and 100 mg doses, respectively. Most interestingly, those receiving the highest dose experienced an 

Although clinical trials with herbal drugs are feasible, few well-controUed doubleblind (placebo-controlled) trials have been carried out with herbal medicines. Several factors might contribute to the explanation of such discrepancies, for example  

However, a large number of clinical trials have been performed with some herbal drugs, including  

Matricaria chamomilla (chamomile) recommended as a carminative, antiinflammatory and antispasmodic  

Silybium marianun (milk thistle) used for repairing liver function including cirrhosis  

Valeriana officinalis (valerian) used as a sedative and sleeping aid  

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The preclinical trials are performed in in vitro and animal studies to assess the biological activity of the new compound. In phase 1 of the clinical trials the safety of a new drug is examined and the dosage is determined by administering the compound to about 20 to 100 healthy volunteers. The focus in phase II is directed onto the issues of safety, evaluation of efficacy, and investigation of side effects in 100 to 300 patient volimteers. More than 1000 patient volunteers are treated with the new drug in phase 111 to prove its efficacy and safety over long-term use. 

FK-506 (37) interferes with IL-2 synthesis and release and has a cyclosporin-like profile, but is considerably more potent in vitro. IC q values are approximately 100-fold lower. This neutral macroHde suppresses the mixed lymphocyte reaction T-ceU proliferation generation of cytotoxic T-ceUs production of T-ceU derived soluble mediators, such as IL-2, IL-3, and y-IFN and IL-2 receptor expression (83). StmcturaHy, FK-506 is similar to sirolimus. Mycophenolate mofetil (33), brequinar (34), and deoxyspergualin are in various phases of clinical evaluation. Identification of therapeutic efficacy and safety are important factors in the deterrnination of their utiUty as immunosuppressive agents. 

Outdated Human Blood. If clinical efficacy and safety of hemoglobin solutions can be shown, the demand for product would soon outstrip the supply of outdated human blood. About 12 million units of blood (1 unit 480 mL) are used in the United States each year, and only about 500,000 outdate. The primary use of blood is in intraoperative and emergency settings. The quantity of blood available for use in production of blood substitutes depends on safety and efficient usage of blood products as well as on the demands on blood suppHes. 

Clinical studies with Norplant attest to its high contraceptive efficacy and safety. The main reason patients request the removal of Norplant is unpredictable vaginal bleeding episodes followed by amenorrhea. The bleeding problem is an unavoidable sequela of progestogen-only contraception. 

Several other antigens with good immunocontraceptive potential have been identified and investigated in laboratory animals. In most studies, the rate and duration of the immunocontraceptive effect are less than acceptable. A potential problem in immunological approaches to antifertUity research is the need for a safe, effective adjuvant and suitable animal models for evaluating the efficacy and safety of methods (111). Newer and more effective adjuvants are required for contraceptive vaccines and vaccines in general. 

Approvability. The product must be able to meet satisfactory criteria for efficacy and safety such that it is approvable by regulatory agencies responsible for the protection of patients. 

For the past few years, however, there has been a hiatus in the pace of discovery of novel medicinal agents. It has been postulated by some that the field has now slowed down due to the limitations of the almost strictly empirical approach that has been applied to date to drug development. It is possible, too, that the higher standards of efficacy and safety that a new drug must meet today, combined with the enormously increased costs of clinical trials, have acted to keep all but the most promising new drugs off the market. 

In the late 1990s, MTBE came under serious attack on grounds of both efficacy and safety. A report by the National Research Council (1999) stated that the addition of oxygen additives in gasoline, including MTBE and ethanol, are far less important in controlling pollution than emission control equipment and technical improvement to vehicle engines and exhaust systems. 

Hirsh J, Warkentin TE, Shaughnessy SG et al (2001) Heparin and low-molecular-weight heparin mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 119(Suppl.) 64S-94S... 

Site directed delivery This approach of conjugating av 33 integrin ligand with a chemotherapeutic agent for optimal efficacy and safety in cancer is under investigation. Earlier work demonstrated the validity of this concept [10]. 

Cholesterol Treatment Trialists (CTT) Collaborators (2005) Efficacy and safety of cholesterol-lowering treatment prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 366 1267-1278... 

Purpose Confirm therapeutic efficacy and safety (indications for use, recommended dosage, contraindications, long-term administration and emergence of additional side effects)... 

Bouza C, Magro A, Munoz A, et al Efficacy and safety of naltrexone and acamprosate in the treatment of alcohol dependence a systematic review. Addiction 99 811-828, 2004... 

Mason BJ, RitvoEC, Morgan RO, etal A double-blind, placebo-controlled pilot study to evaluate the efficacy and safety of oral nalmefene HCL for alcohol dependence. Alcohol Clin Exp Res 18 1162-1167, 1994... 

Ultrarapid detoxification employs general anesthesia and opioid antagonists to accomplish withdrawal more quickly (Alvarez and Carmen del Rio 1999 Bell et al. 1999 Brewer et al. 1998 Brewer and Maksoud 1997 Gerra et al. 2000 Kleber 1998 Rabinowitz et al. 1998 SanandArranz 1999 Shreeram et al. 2001 Stephenson 1997 Strang et al. 1997). Its efficacy and safety are being studied. 

Efficacy. A pivotal study by Hurt et al. (1997) established the efficacy and safety of bupropion SRfor treatment of nicotine dependence, which led to its approval for this indication by the FDA in 1998. This study was a 7-week, double-blind, placebo-controUed, multicenter trial of three doses of bupropion SR (100 mg/day, 150 mg/day, or 300 mg/day in twice daily dosing). Patients were 6l5 cigarette smokers who smoked at least 15 cigarettes/day. The medication was administered in combination with weekly individual cessation counseling. End-of-trial 7-day point prevalence cessation rates were 19.0% for placebo and 28.8%, 38.6%, and 44.2% for the 100 mg/day, 150 mg/day, and 300 mg/day bupropion doses, respectively. At 1-year follow-up, cessation rates were 12.4% for placebo and 19.6%, 22.9%, and 23.1% for the 100 mg/day,... 

Lawrence et al. [66] in a split face study, compared the efficacy and safety of Jessner s solution and 35% TCA with 5% fluorouracil in the treatment of widespread facial actinic keratoses. Fifteen patients were treated. Both treatments reduced the number of visible actinic keratoses by 75%. Similarly, both caused equivalent reductions in keratinocyte atypia, hyperkeratosis, and parakeratosis. Compared to fluorouracil, only one application of the peel was necessary. 

Sefton J, Kligman AM, Kopper SC, Lue JC, Gibson JR (2004) Photodamage pilot study a double-blind, vehicle-controlled study to assess the efficacy and safety of tazarotene 0.1% gel. J Am Acad Dermatol 43 656-663... 

Thiboutot D, Thieroff-Ekerdt R, Graupe K (2003) Efficacy and safety of azelaic acid (15%) gel as a new treatment for papulopustular rosacea results from 2 vehicle-controlled, randomized, phase III studies. J Am Acad Dermatol 48 836-845... 

Persson GB, Chung KF, Bousquet J. Kerstjens HA, Fox H, Thirlwell J, Cioppa GD Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma. Clin Exp Allergy 2004 34 632-638. 

Muller UR, Helbling A, Berchtold E Immunotherapy with honey bee and yellow jacket venom is different regarding efficacy and safety. J Allergy Clin Imm- 48 unol 1992 89 529-535. 

Prevention and Emergency Treatment 151 Immunotherapy 151 Efficacy and Safety... 

When choosing a particular solvent for a specific application a wide range of factors should be considered, including some not directly related to the specific application. Obviously cost, efficacy and safety need to be considered first, and these will generally rule out some options. Following this a more detailed assessment of additional factors should be carried out, ideally including ... 

Corey-Bloom J, Anand R, Veach J, for the ENA 713 B352 Study Group (1998). A randomised trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild and moderately severe Alzheimer s disease. IntJGeriatrPsychopharmacolX, 55-65. 

Rogers SL, Friedhoff LT (1996). The efficacy and safety of Donepezil in patients with Alzheimer s disease results of a US multicentre, randomised, double-blind, placebo-controlled trial. Dementia ,... 

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