Randomized controlled trials in relapsed/refractory follicular lymphoma: a systematic review and meta-analysis.

This systematic literature review evaluated the clinical efficacy and safety of interventions used in relapsed/refractory follicular lymphoma. Primary efficacy outcomes were objective response rate, progression-free survival and overall survival. Safety endpoints were grade 3/4 toxicities, serious adverse events and withdrawals or deaths due to toxicity. Studies were selected if they were randomized controlled trials reporting on the efficacy or safety of treatments for relapsed or refractory follicular lymphoma, and if outcomes were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 10 randomized controlled trials of treatments for relapsed/refractory follicular lymphoma. The most prominent drug investigated (alone or in combination) was rituximab. Most trials did not report median overall survival. Two trials reported median event-free survival (range, 1.2-23.2 months). Six of ten trials reported objective response rate (range, 9-93%). Meta-analysis showed only one statistically significant result: rituximab + bortezomib yielded a significantly higher objective response rate than rituximab monotherapy (relative risk, 1.28; 95% confidence interval, 1.11-1.47). Otherwise, there were no discernable differences in overall survival or progression-free survival, partly due to insufficient reporting of results in the clinical trials. The relatively small number of randomized controlled trials, few overlapping treatment arms, and variability in the randomized controlled trial features and in the endpoints studied complicate the formal comparison of therapies for relapsed/refractory follicular lymphoma. Additional well-designed randomized controlled trials are needed to fully understand the relative outcomes of older and more recently developed therapies.

Randomized controlled trials in relapsed/refractory chronic lymphocytic leukemia: a systematic review and meta-analysis.

This systematic literature review with meta-analysis was conducted on the clinical efficacy and safety of interventions used in the treatment of chronic lymphocytic leukemia (CLL). We systematically searched databases (PubMed, Cochrane Library, and Embase; 1997 to August 2, 2012), conference abstracts, bibliographic reference lists, recent reviews, and Clinicaltrials.gov. Primary efficacy outcomes were objective response rate, progression-free survival, and overall survival. Safety end points were Grade 3/4 toxicities, serious adverse events, withdrawals because of toxicity, and deaths due to toxicity. Studies were selected if they were randomized controlled trials (RCTs) reporting on the efficacy or safety of relapsed or refractory CLL and if outcomes for CLL were reported separately from trials that included other lymphoid neoplasms. We used the Bucher method for conducting adjusted indirect comparisons within a meta-analysis. We identified 6 RCTs of pharmacologic treatment for relapsed/refractory CLL. The most common drugs investigated (alone or in combination) were fludarabine and cyclophosphamide. When reported, median overall survival ranged from 27.3 to 52.9 months, and overall response rate from 58% to 82%. Although meta-analysis of efficacy results was considered, details are not presented because only 3 studies qualified and the common comparator treatment was not clinically relevant. The relatively small number of RCTs, few overlapping treatment arms, and variability in end points studied make it difficult to formally compare therapies for relapsed/refractory CLL. Significant variability in RCT features presents a further challenge to meaningful comparisons. Additional well-designed RCTs are needed to fully understand the relative efficacy and safety of older and more recently developed therapies.

Clinical efficacy and safety in relapsed/refractory mantle cell lymphoma: a systematic literature review.

A systematic literature review was performed to collect and review information on the clinical efficacy and safety of treatments for relapsed/refractory (R/R) mantle cell lymphoma (MCL), with a meta-analysis, if possible. PubMed, Embase, and the Cochrane Library were searched for studies published in English from January 1, 1997, to August 2, 2012. Conference proceedings, bibliographic reference lists of included articles, recent reviews, and ClinicalTrials.gov were searched for phase II to IV studies displaying results. Studies were included if they reported on patients with R/R MCL who were ineligible to receive high-dose chemotherapy with stem cell transplant. Studies of patients with several non-Hodgkin lymphoma subtypes were only included if they reported MCL outcomes separately. We identified 59 studies in R/R MCL. Forty distinct treatment regimens were evaluated. Thirty studies included more than 15 patients with R/R MCL. Six studies were comparative (including 5 randomized controlled trials [RCTs]); 53 were single-arm. There were no common treatments among the RCTs; therefore, a meta-analysis was not feasible. Thirty-one of 59 studies reported baseline data for patients with R/R MCL. Of the 30 studies with > 15 patients with R/R MCL, 30 reported overall response rate data, 14 reported progression-free survival (PFS), and 12 reported overall survival (OS). The small number of RCTs in R/R MCL precludes identifying an optimal treatment. Small sample sizes, infrequent reporting of OS and PFS, and limited information on patient characteristics made a comparison of results difficult. High-quality comparative studies of novel therapies that have the potential to demonstrate OS advantages in R/R MCL are needed.

Clinical efficacy and safety in relapsed/refractory diffuse large B-cell lymphoma: a systematic literature review.

This systematic literature review was designed to assess information on the clinical efficacy and safety of interventions used in the treatment of refractory or relapsed diffuse large B-cell lymphoma (R/R DLBCL) and to perform a meta-analysis if possible. We searched databases (PubMed, EMBASE, and Cochrane Library for articles from 1997 to August 2, 2012 reported in English), conference abstracts, bibliographic reference lists, and the ClinicalTrials.gov database for phase II to IV studies with results. Studies had to report on patients with R/R DLBCL who were not eligible to receive high-dose therapy (HDT) with stem cell transplantation (SCT) (autologous or allogeneic). Mixed-type non-Hodgkin lymphoma (NHL) studies were required to report R/R DLBCL outcomes separately. We identified 55 studies that presented outcomes data separately for patients with R/R DLBCL. Of 7 comparative studies, only 4 were randomized controlled trials (RCTs). In the 2 RCTs with a common regimen, the patient populations differed too greatly to perform a valid meta-analysis. The 48 single-arm studies identified were typically small (n < 50 in most), with 31% reporting median progression-free survival (PFS) or overall survival (OS) specifically for the R/R DLBCL population. In these studies, median OS ranged from 4 to 13 months. The small number of RCTs in R/R DLBCL precludes identifying optimal treatments. Small sample size, infrequent reporting of OS and PFS separated by histologic type, and limited information on patient characteristics also hinder comparison of results. Randomized studies are needed to demonstrate which current therapies have advantages for improving survival and other important clinical outcomes in patients with R/R DLBCL.

Adoption and use of health information technology in physician practice organisations: systematic review.

BACKGROUND: Health information technology (HIT) has the potential to improve clinical outcomes, increase health provider productivity and reduce healthcare costs. Over half of all patient care is delivered in physician practice organisations, yet adoption and utilisation of HIT in these groups lags behind inpatient facilities. OBJECTIVE: To better understand current utilisation rates along with benefits and barriers to HIT adoption in physician practice organisations. METHODS: Published literature on the adoption and use of HIT in physician practice organisations within the USA between 12 January 2004 and 12 January 2009 and indexed in MEDLINE and EMBASE was included in the systematic review. Grey literature was also searched. Studies related to the adoption and use of HIT in hospitals and community health centres were excluded. RESULTS: A total of 119 articles were eligible for inclusion in the review. Adoption rates across physician groups remain low, with between 9% and 29% of practices having implemented electronic medical records. HIT improves clinical outcomes, increases the use of vaccinations and improves medication adherence. Furthermore, HIT adoption leads to cost savings for physician groups, improves staff productivity and enriches patient-provider interactions. The largest barrier to HIT adoption in physician groups is the high initial and ongoing costs of electronic systems. Lack of sufficient training, a disorganised or non-receptive practice culture and technological problems such as inadequate connectivity appear to impede effective HIT use. CONCLUSIONS: HIT has the potential to positively impact on physician practice organisations, although significant and diverse barriers block adoption. Research into these obstacles should be coupled with efforts to understand barriers to effective implementation after HIT adoption.