Randomized controlled trials patient safety

Treatment of symptomatic diverticular disease of the colon is aimed at the relief of symptoms and the prevention of major complications. The efficacy of fiber supplementation and of anticholinergic and spasmolytic agents remains controversial. Antibiotics are commonly used in the treatment of inflammatory complications of diverticular disease. Data from open labelled and randomized controlled trials do suggest the efficacy of rifaximin in obtaining symptomatic relief in patients with diverticular disease. Approximately 30% therapeutic gain compared to fiber supplementation only can be expected after one year of intermittent treatment with rifaximin. Considering the safety and tolerability of rifaximin, this drug can be recommended for patients with symptomatic uncomplicated diverticular disease. 

Pharmacokinetic studies in patients yielded an estimated product half-life of approximately 20 days (11-50 days range) and the product clearance was found to be variable according to body weight, gender and tumour burden. Safety and efficacy were established by three randomized, controlled trials. The first study was a randomized double-blind trial involving 813 patients. The primary end-point measured was overall survival, which was extended from a median of 15.6 months to 20.3 months. 

Roskos LK, Boudinot ED Effects of dose and sex on the pharmacokinetics of piroxicam in the rat. Biopharm Drug Dispos 11 215-225, 1990 Rosier M, Anand R, Cici-Sain A, et al Efficacy and safety of rivastigmine in patients with Alzheimer s disease international randomized controlled trial. BMJ 318 633-640, 1999... 

Blazing MA, de Lemos JA, White HD, et al., for the A to Z Investigators, Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin A randomized controlled trial. JAMA 2004 292 55-64,... 

The combination of clozapine and lithium has been studied in a randomized controlled trial in 10 patients with schizophrenia and 10 with a schizoaffective disorder taking clozapine with either lithium or placebo for 4 weeks (299). The combination was well tolerated, except for reversible neurotoxic reactions in two patients with schizophrenia, and safety measures showed no significant variations. The authors concluded that the lithium added to clozapine appears to afford potential benefit in schizoaffective disorders without harmful effects for schizophrenia, however, it did not afford improvement but posed a risk of lithium toxicity. 

The qnestion of whether digoxin shonld be nsed to treat patients with mild to moderate heart faUnre in sinns rhythm, in the wake of randomized, controlled trials of its efficacy, inclnding PROVED, RADIANCE, and DIG (SEDA-18,196) (SEDA-20,173), has been reviewed (62). The anthors conclnded that digoxin is effective in prodn-cing symptomatic improvement in patients with mild or moderate heart faUnre, bnt that becanse of concerns abont its safety carefnl consideration mnst be taken in each case before nsing it. 

Richter JE, Kahrilas PJ, Johanson J, Maton P, Breiter JR, Hwang C, Marino V, Hamelin B, Levine JG, Esomeprazole Study Investigators. Efficacy and safety of esomeprazole compared with omeprazole in GERD patients with erosive esophagitis a randomized controlled trial. Am J Gastroenterol 2001 96(3) 656-65. 

Lalezari JP, Holland GN, Kramer F, McKinley GF, KemperCA, Ives DV, Nelson R, Hardy WD, Kupperman BD, Northfelt DW, Youle M, Johnson M, Lewis RA, Weinberg DV, Simon GL, Wolitz RA, Ruby AE, Stagg RJ, Jaffe HS. Randomized, controlled trial of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. J AIDS Hum Retrovirol 1998 17 339-344. 

As part of the analysis and critique of both CAM and conventional modalities, integrative medicine practitioners search for accurate information in texts, primary literature, and the Internet to counsel their patients on the relative efficacy, safety, and appropriate use of these therapies. To ensure validity of research findings, it is becoming increasingly evident that other methodologies, in addition to the randomized controlled trial, need to be conceived and completed to fully evaluate these unconventional therapies as well as the integrative medical model itself. 

Several novel agents have been tried in bipolar disorder, but randomized controlled trials are needed to determine their efficacy and safety. High doses of levothyroxine sodium (0.15 to 0.4 mcg/day) have been reported to have mood-stabilizing properties in rapidcycling bipolar patients when combined with traditional mood-stabilizing agents. ... 

Apfel S C, Schwartz S, Adornato B T, et al. (2000). Efficacy and safety of recombinant human nerve growth factor in patients with diabetic polyneuropathy A randomized controlled trial. rhNGF Clinical Investigator Group. J. Amer. Med. Associ. 284 2215-2221. 

Askling J, Fahrbach K, Nordstrom B, Ross S, Schmid CH, and Symmons D. 2011. Cancer risk with tumor necrosis factor alpha (TNF) inhibitors meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data. Pharmacoepidemiology and Drug Safety 20 119-130. 

Khemis A, Kaiafa A, QueiUe-Roussel C et al (2007) Evaluation of efficacy and safety of rudnol serum in patients with melasma a randomized controlled trial. Br J Dermatol 156 997-1004... 

Nelson H, Bonuccelli C, Radner F, Ottosson A, Carroll KJ, Andersson TL, LaForce C. Safety of formoterol in patients with asthma combined analysis of data from double-blind, randomized controlled trials. J Allergy Clin Immunol 2010 125(2) 390-6.e8. 

---