Clinical trials patient safety

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. 

Nesiritide has been shown to improve symptoms of dyspnea and fatigue. In a randomized clinical trial, the safety and efficacy of adding nesiritide to standard care was compared to placebo and nitroglycerin.53 Nesiritide was found to significantly decrease PCWP more than nitroglycerin and placebo over 3 hours. Nesiritide improved patients self-reported... 

Becker MA, Schumacher HR, Wortmann RL, MacDonald PA, Palo WA, Eustace D et al. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase a twenty-eight-day, multicenter, phase II, randomized, double-blind, placebo-controlled, dose-response clinical trial examining safety and efficacy in patients with gout. Arthritis Rheum 2005 52(3) 916-23. 

In clinical trials the safety profile of aztreonam was similar to or better than that of other more conventional beta-lactam antibiotics, in adult patients with both normal renal function (3,4) and impaired renal function (5). These findings have been confirmed in children (6). 

HA has been used as a hydrophihc carrier to deliver diclofenac topically for the treatment of premalignant skin lesions such as actinic keratoses (AK) (106-112) and for colon-26 adenocarcinoma (113-115). HA is the preferred carrier for transdermal delivery of diclofenac, as it has been shown to enhance the partitioning of the drug into the skin compared to other vehicles (116). Furthermore, in a clinical trial, the safety and efficacy of 3% diclofenac in 2.5% HA gel have been evaluated as a topical treatment for actinic keratosis (108). Patients treated with HA-diclofenac showed significantly lower target and cumulative lesion number scores and lesion total thickness scores compared to the placebo group. The treatment with 3.0% diclofenac in 2.5% HA gel was effective when used for 60 days and was well tolerated in patients with AK. 

At the conclusion of a clinical trial, patients may be continued on treatment and followed-up for a period of months or years, generating more long-term safety experience (these are known as open-label extensions). When clinical trials are conducted entirely after marketing, they may provide important new safety information provided that they contain enough patients, and have few exclusion criteria and clinically relevant outcomes that are easily measured (e.g. mortality). Such studies are often called large simple trials. ... 

In clinical trials, patients were identified based on the molecular analysis using the same diagnostic kit from Abbott employed to detect ALK fusions. Crizotinib was administrated orally at the standard dose of 250 mg twice daily in a 28-day cycles. Based on a cohort of 50 advanced NSCLC patients with ROS 1 rearrangement, the ORR was 72%. The safety profile of crizotinib in these new patient populations was similar to that observed in patients harboring ALK-fusion mutations. For example, the most common treatment-related adverse effects (grade 3) were hypophosphatemia, neutropenia, and an elevated alanine aminotransferase level. There were no treatment-related grade 4 or 5 adverse events in the ROSl patients." ... 

The first study to demonstrate the activity of enfuvirtide in HIV-infected patients (Kilby et al. 1998) showed that patients receiving the maximum 100 mg intravenous dose had maximum median declines in HIV-1 RNA of -1.96 logjo copies/mL through 14 days. Several additional studies (Kilby et al. 2002 Lalezari et al. 2003a, b) further demonstrated the safety and efficacy of enfuvirtide and led to the selection of twice-daily subcutaneous injections of a 90 mg nominal dose for testing in the TORO (T-20 vs. optimized regimen only) pivotal clinical trials. 

The PRO ACT-11 trial was designed to assess the clinical efficacy and safety of lA r-pro-UK. In this study, 180 patients were enrolled in a 2 1 randomization scheme to receive either 9 mg lA r-pro-UK plus 4 hours of low-dose IV heparin, or low-dose IV heparin alone. The primary clinical outcome, the proportion of patients with slight or no disability at 90 days (mRS of < 2), was achieved in 40% of the 121 patients in the r-pro-UK treatment group, compared to 25% of the 59 patients in the control group (absolute benefit 15%, relative benefit 58%, number need to treat = 7 p = 0.04). The recanalization rate (TlMl 2 and 3) was 66% for the r-pro-UK group and 18% for the control group (p < 0.001). Symptomatic ICH within 24 hours occurred in 10% of r-pro-UK patients and 2% of control patients (p = 0.06). All symptomatic ICHs occurred in patients with a baseline NIHSS... 

The exact role of rituximab in RA is not clearly defined, but it is indicated for patients with moderate to severe RA with a history of inadequate response to DMARDs and other BRMs. Rituximab carries a black-box warning of fatal infusion reactions and severe mucocutaneous reactions even though these events did not occur during the RA clinical trials. The benefits of rituximab must be tempered against the safety concerns reported with use of rituximab in the oncology setting. 

A cancer patient may encounter many different health care professionals phlebotomists, pathologists, surgeons, medical and radiation oncologists, physician assistants, pharmacists, nurses, counselors, dieticians, social workers, and chaplains all may be involved with a single patient. Each one plays an important role in care of the cancer patient. The pharmacist s role may include education of patients and family members, education of staff about new agents and safety issues, preparation of therapies, resolution of reimbursement issues, development of order sets, and participation in clinical trials. Each patient should have access to an interdisciplinary team to assist him or her during treatment. 

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