US Trial Research Articles

Interventions for trichomoniasis in pregnancy.

Vaginitis due to Trichomonas vaginalis is one of the most common of sexually transmitted diseases. Trichomoniasis affects women during pregnancy as well but it is not clearly established whether it causes preterm birth and other pregnancy complications. The objective of this review was to assess the effects of various treatments for trichomoniasis during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (14 January 2011). Randomized trials comparing anti-trichomonas agents during pregnancy. Trials including symptomatic or asymptomatic women with trichomoniasis were eligible. Two review authors assessed eligibility and trial quality. We included two trials with 842 pregnant women. In both trials around 90% of women were cleared of trichomonas in the vagina after treatment. In the US trial, women with asymptomatic trichomoniasis between 16 and 23 weeks were treated with metronidazole on two occasions at least two weeks apart. The trial was stopped before reaching its target recruitment because metronidazole was not effective in reducing preterm birth and there was a likelihood of harm (risk ratio 1.78; 95% confidence interval 1.19 to 2.66). The South African trial recruited women later in pregnancy and did not have the design and power to address adverse clinical outcomes. We excluded two recent studies, identified for the current update, because they did not address the primary question. Metronidazole, given as a single dose, is likely to provide parasitological cure for trichomoniasis, but it is not known whether this treatment will have any effect on pregnancy outcomes. The cure rate could probably be higher if more partners used the treatment.

One-Year Data from the RESOLUTE US Trial

One-Year Data from the RESOLUTE US Trial

Valves aortiques percutanées : résultats actuels et perspectives

As the French population is aging, a growing number of elderly patients with symptomatic severe aortic stenosis are going to require therapeutic management. Approximately 30 to 40% of these patients do not undergo surgical treatment and a high proportion is considered to be at high risk for surgery. The transluminal aortic valve implantation technique has been increasingly used over the past few years, thus providing a solution to a major therapeutic issue in our industrialized countries. While the cardiology community was rapidly convinced of its efficacy, remaining doubts regarding the outcome of this technique in terms of mortality were erased by the recent publication of results achieved in cohort B of the Partner US trial. This new approach is clearly here to stay and should soon reach a maturity phase with respect to its indications, the selection of patients and technical aspects.

Exploratory Analyses of Efficacy Data From Major Depressive Disorder Trials Submitted to the US Food and Drug Administration in Support of New Drug Applications

There has been concern about a high rate of placebo response and a substantial failure rate in recent clinical trials in major depressive disorder (MDD). This report explores differences in efficacy data from placebo-controlled MDD trials submitted in support of new drug applications (NDAs) over a 25-year period. We compiled efficacy data from 81 randomized, double-blind clinical trials, with 21,611 evaluable patients, that were submitted to the US Food and Drug Administration as part of NDAs for an antidepressant claim between 1983 and 2008. Trial data were limited to completed, randomized, multicenter, double-blind, placebo-controlled clinical trials in adult patients diagnosed with MDD according to DSM-III or DSM-IV criteria. The database was further limited to patients who were involved in clinical trials for drugs widely viewed as effective antidepressants and for doses of these drugs also viewed as effective doses. Trials were rated as successful if they showed statistical superiority vs placebo for the investigational drug on change in Hamilton Depression Rating Scale (HDRS) score (last-observation-carried-forward data). (Trials with multiple investigational drug groups were successful if there was superiority in at least 1 drug group after adjustment for multiplicity.) In particular, we explored differences in effect size and success rate of these trials, based on when the studies were conducted, geographic location of the study sites (US vs non-US), trial duration, dosing regimen, study size, and baseline disease characteristics. Eighty-one percent of MDD patients were enrolled in US sites. Although the observed placebo and drug responses at non-US sites tended to be larger than at US sites, the treatment effect (drug-placebo difference) was similar (mean change from baseline of about -2.5 units in HDRS total score) in US and non-US trials. In both US and non-US trials, the placebo response showed a modest increase over the observation period (1983-2008). Treatment effect clearly diminished over this same period, at a similar rate for both US and non-US trials despite a marked increase in the sample size of the trials. Our analysis showed that 53% of all MDD trials in the last 25 years were successful. US trials had a higher success rate than non-US trials (58% vs 33%). Before 1995, the overall success rate was 55%, compared to 50% for trials in 1995 or later, and, in general, 6-week trials had a higher success rate than 8-week trials (55% vs 42%). It should be noted that the earlier trials were mostly 6 weeks, and the 6-week trials had higher mean baseline HDRS scores than the 8-week trials. Study size did not seem to influence trial success rates. Mean baseline HDRS total scores declined over the 25-year observation period for patients in both US and non-US trials, as did treatment effect in these trials, again, regardless of region. Fixed-dose trials had a numerically slightly greater success rate than flexible-dose trials (57% vs 51%), although on average treatment effect was numerically larger in the flexible-dose trials than in fixed-dose trials (mean of -2.9 vs -2.0 on HDRS units). Treatment effect has declined over time in MDD trials, and there has been a high failure rate for these trials during the entire period, but the reasons for these findings remain elusive. Baseline disease severity seems to be a more important factor in study outcome than study duration, dosing regimen, sample size, time when studies were conducted, and regions where data were generated. Close attention is needed to a variety of factors in the design and conduct of these studies, including patient population, diagnostic considerations, patient assessment, and clinical practice differences. These considerations become increasingly important as globalization of clinical trials continues to increase.

Clinical Evaluation of the Resolute Zotarolimus-Eluting Coronary Stent System in the Treatment of De Novo Lesions in Native Coronary Arteries: The RESOLUTE US Clinical Trial

The RESOLUTE US (R-US) trial is a prospective, observational study designed to evaluate the clinical effectiveness of the Resolute zotarolimus-eluting stent (R-ZES) in a U.S. population. The R-ZES releases zotarolimus over a 6-month period in order to achieve optimal clinical effectiveness and safety. The R-US trial recruited patients with de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents from 2.25 to 4.0 mm in diameter. In the main analysis cohort (2.5- to 3.5-mm stents and single-lesion treatment), the primary endpoint was 12-month target lesion failure (TLF) defined as the composite of cardiac death, myocardial infarction (MI), and clinically-driven target lesion revascularization (TLR), compared with data from Endeavor zotarolimus-eluting stent (E-ZES) trials, adjusting for baseline covariates through propensity scores. Overall, 1,402 patients were enrolled with a mean reference vessel diameter of 2.59 ± 0.47 mm and diabetes prevalence of 34.4%. In the main analysis cohort, TLF was 3.7% at 12 months compared with historical E-ZES results (TLF = 6.5%). The R-ZES met the 3.3% margin of noninferiority (rate difference = -2.8%, upper 1-sided 95% confidence interval: -1.3%, p < 0.001). The overall TLF rate was 4.7%, and rates of cardiac death, MI, and TLR were 0.7%, 1.4%, and 2.8%, respectively. The 12-month rate of stent thrombosis was 0.1%. The R-ZES achieved a very low rate of clinical restenosis while maintaining low rates of important clinical safety events such as death, MI, and stent thrombosis at 1-year follow-up. (The Medtronic RESOLUTE US Clinical Trial [R-US]; NCT00726453).

Rationale and design of the clinical evaluation of the Resolute Zotarolimus-Eluting Coronary Stent System in the treatment of de novo lesions in native coronary arteries (the RESOLUTE US clinical trial)

Drug-eluting stents (DES) are commonly used to treat obstructive coronary disease and avoid restenosis. Newer DES have been developed to improve effectiveness and safety. We describe a clinical trial to evaluate a DES with a novel polymer that may improve the antirestenosis effectiveness while maintaining the safety standards of currently Food and Drug Administration-approved DES. The RESOLUTE US Trial is a multicenter, nonrandomized trial prospectively designed to compare the Resolute zotarolimus-eluting stent (R-ZES) to the Food and Drug Administration-approved Endeavor ZES using patient-level historical control data, adjusting for baseline covariates through propensity score. The stents differ primarily in the polymer, which, in the R-ZES, is designed to elute zotarolimus over a longer period. The study will enroll up to 1,574 patients with ischemic heart disease due to de novo native coronary lesions suitable for 1- or 2-vessel treatment with stents from 2.25 to 4.0 mm in diameter. The primary end point is target lesion failure at 12 months postprocedure, defined as the composite of cardiac death, target-vessel myocardial infarction (MI), and clinically driven target lesion revascularization by percutaneous or surgical methods. Secondary end points include device, lesion and procedural success, death, MI, cardiac death and MI, composites of these clinical events, and stent thrombosis at each follow-up assessment up to 5 years postprocedure. The RESOLUTE US Trial (ClinicalTrials.gov #NCT00726453) is a prospective, multicenter, observational study with a patient-level historical control designed to assess the safety and efficacy of the R-ZES for the treatment of de novo lesions in native coronary arteries.

BMS Gains Expanded Territorial Rights to Anti-PD-1 Antibody from Ono Pharmaceutical

In exchange for Japanese co-development and co-commercialisation rights to its rheumatoid arthritis biologic Orencia® (abatacept), Bristol-Myers Squibb (BMS) has gained expanded territorial rights from Ono Pharmaceutical to BMS-936558/ONO-4538, an anti-programmed cell death (PD-1) antibody in Phase I and II clinical trials in the US for a number of tumour types. BMS already had rights to develop and commercialise the cancer immunotherapy in North America as a result of its 2009 acquisition of Medarex and it now has rights in the rest of the world, except in Japan, Korea and Taiwan.

Meta-analysis of randomised trials comparing thiopurines in childhood acute lymphoblastic leukaemia

Mercaptopurine has been used in continuing treatment for childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated thioguanine might be more effective than mercaptopurine. The US and UK cooperative groups began randomized thiopurine trials and agreed prospectively to a meta-analysis. All randomized trials of thioguanine versus mercaptopurine were sought and data on individual patients were analysed by standard methods. Combining three trials (from US, UK and Germany), the overall event free survival (EFS) was not significantly improved with thioguanine (Odds ratio (OR) = 0.89; 95% confidence interval 0·78–1·03). Apparent differences in results between trials may be partly explained by the different types of patients studied. The larger treatment effect reported in males in the US trial was confirmed in the other trials. There was heterogeneity between sex/age subgroups (p=0·001), with significant EFS benefit of thioguanine only seen for males aged under 10 years old (OR=0·70; 0·58–0·84), although this did not result in a significant difference in overall survival (OR=0·83; 0·62–1·10). Additional toxicity occurs with thioguanine. Mercaptopurine remains the standard thiopurine of choice, but further study of thioguanine may be warranted to determine whether it may benefit particular subgroups.

Influence of Publication of US and European Prostate Cancer Screening Trials on PSA Testing Practices

In 2009, results from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial indicated no difference in mortality between the screening and the control groups (rate ratio = 1.13, 95% confidence interval = 0.75 to 1.70), whereas those from the European Randomized study of Screening for Prostate Cancer trial indicated a 20% reduction in mortality among the screening group (rate ratio = 0.80, 95% confidence interval = 0.65 to 0.98). In this study, we examined whether prostate-specific antigen (PSA) testing has changed following these publications. The primary outcome measure was the proportion of men seen at least once in a primary care or urology clinic between August 1, 2004, and March 31, 2010, who received a PSA test. Following the publications, PSA use declined slightly-by 3.0 percentage points and 2.7 percentage points among men aged 40-54 and 55-74 years, respectively. PSA testing among men older than 75 years initially declined slightly following the recommendations by the US Preventive Services Task Force in 2008 and continued to decline after the trial publications.

House dust mite sublingual immunotherapy: Results of a US trial

Few trials of sublingual immunotherapy (SLIT) in the United States have been reported. This randomized, placebo-controlled feasibility SLIT study compared the safety and physiologic effects of high- versus low-dose Dermatophagoides farinae vaccine. Thirty-one D farinae-sensitive adults with allergic rhinitis with or without mild intermittent asthma were eligible for randomization to high-dose maintenance vaccine (n = 10, 4200 allergen units [approximately 70 μg of Der f 1/d]), low-dose maintenance vaccine (n = 10; 60 allergen units [approximately 1 μg of Der f 1/d]), or placebo (n = 11) over 12 to 18 months. Medication-symptom scores and adverse events were monitored, serum D farinae-specific IgE and IgG4 levels were measured, and bronchial reactivity to D farinae was determined at baseline and 6-month intervals. Of the 31 randomized subjects, 6 withdrew because of non-treatment-ascribed events. Four withdrew because of treatment-ascribed effects: high-dose group, 1 of 10 (gastrointestinal symptoms); low-dose group, 1 of 10 (gastrointestinal symptoms); and placebo group, 2 of 11 (headache and increased nasal symptoms). Thus 21 subjects completed the study: high-dose group, 9; low-dose group, 7; and placebo group, 5. Eleven of the 21 subjects experienced mild-to-moderate gastrointestinal symptoms, throat irritation, or both (high-dose group, 5/9; low-dose group, 4/7; and placebo group, 2/5). No severe systemic reactions were noted. No differences in symptom-medication scores were found. High-dose SLIT increased the bronchial threshold to allergen challenge and increased serum D farinae-specific IgG4 levels, whereas low-dose SLIT and placebo had no significant effect. High-dose D farinae SLIT was generally tolerable, increased serum D farinae-specific IgG4 levels, and improved the bronchial threshold to allergen challenge. Larger US trials are warranted.

Transcatheter aortic valve implantation: evidence on safety and efficacy compared with medical therapy. A systematic review of current literature

Transcatheter aortic valve implantation (TAVI) promises effective treatment for high-risk elderly patients with symptomatic severe aortic stenosis (AS). However, the adoption of TAVI must be justified and guarantee long-term performance. Systematic reviews are a core methodology in evidence-based health economics for judging medical effectiveness. In this work, the methodology was applied to provide objective evidence on the efficacy and safety of TAVI at 1-year follow-up and to assess whether TAVI confers a survival benefit compared with medical therapy. In accordance with the toolkit of the "German Scientific Working Group Technology Assessment for Health Care" (GSWG), a systematic literature review on the safety and efficacy of TAVI procedures was conducted in major bibliographic databases to identify all relevant publications. Preestablished inclusion criteria were defined. An initial screening of identified articles regarding titles and abstracts was followed by a full-text screening. Data from eligible articles were extracted and evaluated according to GSWG checklists followed by a qualitative synthesis of information. The systematic literature search identified 12 primary publications (derived from 1,849 citations) for TAVI [number of patients (n)=1,049] and 11 publications (derived from 189 citations) for medical therapy of AS (n=946) that fulfilled the inclusion criteria. Mean overall procedural success rate for included TAVI interventions was 93.3%. Mean combined procedural, post-procedural, and cumulative in-hospital/30-day mortality was 11.4% (n=116; range 5.3-23%). 1year after TAVI, the mean overall survival rate was 75.9% (range 64.1-87%) compared with 62.4% (range 40-84.8%) for medically treated patients (p value<0.01). 1-year survival after TAVI for patients treated with transvascular (TV) procedures was higher than after transapical (TA) procedures (79.2 vs. 73.6%) (p value=0.04). At 1-year follow-up, the improved valvular function remained stable, and there was a trend towards an improved ventricular function. Based on the best available data, in patients with symptomatic severe AS, TAVI demonstrates an improved 1-year survival compared with medical treatment. The survival benefit of TV-TAVI over medical therapy elucidated from this systematic literature review is +16.8% and therefore, in good congruence with the recently published results from the randomized PARTNER US trial (+20%).

Perspective on prostate cancer screening

Cancer screening has become an obligatory appendix to all periodic and continuity care of adults. It is ritualistic and seldom questioned. It is discrete and modular and so easily audited for 'quality'. Its impact on actual health ranges from slightly helpful to slightly harmful, and even these conclusions are usually more than slightly speculative. While, in some cases, the existing data includes the probability of an occasional life saved, all screening programmes increase many-fold the lifetime chance of confronting a false alarm and thus becoming, for a time, a cancer patient.

Selected US Trials in Adult Leukemia/Myelodysplastic Syndrome – Status, November 2010: Open for Enrollment

Selected US Trials in Adult Leukemia/Myelodysplastic Syndrome – Status, November 2010: Open for Enrollment

Brain Metastasis in Melanoma: Clinical Activity of CTLA-4 Antibody Therapy

Melanoma metastasizes frequently to the brain, and brain metastases generally drive the prognosis of melanoma patients. Surgical and radiation therapy improve the outcome of selected melanoma patients with brain metastasis, while systemic treatment using cytotoxic agents still plays a limited role. Temozolomide and fotemustine are preferentially used in melanoma patients with brain metastases in the United States and in Europe, respectively, with modest clinical activity. However, the results obtained with either agent are still limited, and efforts are needed to improve the outcome of these patients who are generally excluded from clinical trials. Among therapeutic agents in development, antibodies that block the interaction of cytotoxic T-lymphocyte-associated antigen (CTLA-4) with its ligands B7.1 and B7.2 and thus enhance antitumor immune responses have shown clinical benefit in patients with metastatic melanoma, including durable control of brain metastases. This chapter reviews the current data and the rationale for ongoing and future trials of combination cytotoxic plus immunomodulatory therapy by US and Italian multicenter trial groups.

Endoscopic radiofrequency ablation for Barrett’s esophagus: 5-year outcomes from a prospective multicenter trial

The AIM-II Trial included patients with nondysplastic Barrett's esophagus (NDBE) treated with radiofrequency ablation (RFA). Complete eradication of NDBE (complete response-intestinal metaplasia [CR-IM]) was achieved in 98.4 % of patients at 2.5 years. We report the proportion of patients demonstrating CR-IM at 5-year follow-up. Prospective, multicenter US trial (NCT00489268). After endoscopic RFA of NDBE up to 6 cm, patients with CR-IM at 2.5 years were eligible for longer-term follow-up. At 5 years, we obtained four-quadrant biopsies from every 1 cm of the original extent of Barrett's esophagus. All specimens were reviewed by one expert gastrointestinal pathologist, followed by focal RFA and repeat biopsy if NDBE was identified. Primary outcomes were (i) proportion of patients demonstrating CR-IM at 5-year biopsy, and (ii) proportion of patients demonstrating CR-IM at 5-year biopsy or after the single-session focal RFA. Of 60 eligible patients, 50 consented to participate. Of 1473 esophageal specimens obtained at 5 years 85 % contained lamina propria or deeper tissue (per patient, mean 30 , standard deviation [SD] 13). CR-IM was demonstrated in 92 % (46 / 50) of patients, while 8 % (4 / 50) had focal NDBE; focal RFA converted all these to CR-IM. There were no buried glands, dysplasia, strictures, or serious adverse events. Kaplan-Meier CR-IM survival analysis showed probability of maintaining CR-IM for at least 4 years after first durable CR-IM was 0.91 (95 % confidence interval [CI] 0.77 - 0.97) and mean duration of CR-IM was 4.22 years (standard error [SE] 0.12). In patients with NDBE treated with RFA, CR-IM was demonstrated in the majority of patients (92 %) at 5-year follow-up, biopsy depth was adequate to detect recurrence, and all failures (4 / 4, 100 %) were converted to CR-IM with single-session focal RFA.

Management of acute attacks of hereditary angioedema: potential role of icatibant.

Icatibant (Firazyr(®)) is a novel subcutaneous treatment recently licensed in the European Union for acute hereditary angioedema. Hereditary angioedema, resulting from inherited partial C1 inhibitor deficiency, is a disabling condition characterized by intermittent episodes of bradykinin-mediated angioedema. Icatibant blocks bradykinin B2 receptors, attenutating the episode. Randomized double-blind, placebo-controlled trials of icatibant, showed significant superiority over oral tranexamic acid in 74 European patients and a trend to improvement in a similar US trial comparing icatibant with placebo in 55 patients. Outcomes for several endpoints did not reach significance in the US trial, perhaps because of low participant numbers and confounding factors: a further trial is planned. Open label studies have shown benefit in multiple treatments for attacks at all sites. Approximately 10% of patients require a second dose for re-emergent symptoms, usually 10 to 27 hours after the initial treatment. Its subcutaneous route of administration, good tolerability and novel mode of action make icatibant a promising addition to the limited repertoire of treatments for hereditary angioedema.

Digest

AbstractDepressionSSRIs and suicide rateSSRI antidepressants have replaced tricyclic antidepressants (TCAs) as the agents of first choice and now account for the majority of antidepressants prescribed. This relatively rapid change has been linked to a decline in the rate of suicide but researchers from Norway have found no evidence to support this (BMC Psychiatry 2010;10:62).They found that suicide rates for all four Nordic countries (Denmark, Finland, Norway and Sweden) were already declining when the SSRIs were introduced in the early 1990s. Sales of antidepressants had increased by about half between 1975 and 1989, and increased fivefold between 1990 and 2006. At that time, SSRIs accounted for about two‐thirds of antidepressant sales. There was no statistical evidence that the increase in SSRI sales or the decrease in TCA sales was associated with a decline in suicide rates and there was no evidence of a lagged response.Recurrence and rate of discontinuationRecurrence of depression or panic occurs sooner after rapid discontinuation of antidepressant therapy than slow discontinuation, say US investigators (Am J Psychiatry 2010;167:934‐41).They compared the effects of clinically‐determined rapid (over one to seven days, 47 per cent) and slow (over 14 days or longer, 53 per cent) discontinuation of antidepressant in 398 patients with depression, panic disorder or bipolar disorder. All patients were attending a tertiary clinic; they had responded well to treatment and were not depressed at the time of discontinuation.Compared with gradual discontinuation, rapid discontinuation was associated with a shorter time to the first new episode of depression or panic (3.6 vs 8.4 months). After rapid discontinuation, the time to a new episode was approximately one quarter of the interval between episodes while taking an antidepressant. Also, after rapid discontinuation, the difference in time to a new episode between tricyclic antidepressants (TCAs) and newer antidepressants was less than one week; after gradual discontinuation, the time to a new episode was five months longer with TCAs than with newer antidepressants.Looking at baseline factors, rapid discontinuation was associated with younger age (by four to five years) and shorter treatment duration (by three months). There was no difference according to diagnosis or type of antidepressant. Rapid discontinuation was 16 times more likely to have been the patient's choice than slow discontinuation.Augmenting antidepressant therapyTwo US trials have evaluated the efficacy of new strategies to augment unsuccessful antidepressant therapy.S‐adenosyl methionine (SAMe) is a methyl donor that occurs naturally in the body; it is available in Europe and marketed in the US as a dietary supplement. Meta‐analysis of several small trials suggests that it may be effective as monotherapy for depression.In 73 patients with depression despite at least six weeks' treatment with an adequate dose of an SSRI, the addition of SAMe 400mg twice daily significantly increased response rate (36 vs 18 per cent with placebo) and remission rate (26 vs 12 per cent), according to Hamilton Depression Rating Scale (HAM‐D) score after six weeks (Am J Psychiatry 2010;167:942‐8). This was supported by Clinical Global Impression (CGI) ratings.• With a slightly different aim in mind, a crossover trial tested whether the NMDA antagonist ketamine could induce a rapid improvement in 18 patients with treatment‐resistant bipolar depression during stable treatment with lithium or valproate (Arch Gen Psychiatry 2010;67:793‐802).Compared with placebo, IV infusion of ketamine 0.5mg per kg improved depression symptom scores within 40 minutes, reaching a peak effect on day 2 (about 10 points on the Montgomery Åsberg Depression Rating Scale (MADRS) score) and persisting through to day 3. The response rate according to the MADRS score was 71 per cent with ketamine and 6 per cent with placebo. The main adverse effect of ketamine was dissociation, though this was recorded only at 40 minutes after administration; one patient in each group developed manic symptoms.The authors say their findings prove the value of targeting the NMDA receptor complex and say further studies are needed to develop a long‐term treatment. Copyright © 2010 Wiley Interface Ltd

A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program

A recent Institute of Medicine (IOM) report (1) cited several deficiencies in the Clinical Trials Cooperative Group Program of the National Cancer Institute (NCI), including an inefficient and cumbersome oversight structure and a 20% reduction in funding since 2002. The authors concluded that these and other problems have resulted in start-up times for phase III Cooperative Group trials that range from 1.25 to almost 7 years and a clinical trial completion rate of only 50%. They also noted that clinical trials of cancer treatments are increasingly located outside the United States. Although the oversight structure and funding decline at the NCI may be partially responsible for the observed problems, demographic and market forces are also likely causes. We searched ClinicalTrials.gov for trials registered since 2005 that involved adult cancer patients and found that planned enrollment in NCI-sponsored clinical trials—the number of patients the investigators intended to enroll at the start of the trial—declined from 2.90% of new US cancer cases in 2005 to 1.79% in 2009 (Table 1). During this same time period, planned enrollment for all other (ie, non–NCI-sponsored) US-based adult clinical trials of cancer treatments increased from 3.24% to 4.62% of new US cancer cases. Table 1 Planned US trial enrollment divided by the number of new US cancer patients These trends illustrate the diminishing role of the NCI in the sponsorship of US-based clinical trials in both absolute and relative terms. As planned enrollment in NCI-sponsored trials has decreased, planned enrollment in commercially sponsored trials has increased. Whether a more efficient and better funded NCI would have been able to prevent this trend is debatable. Planned enrollment for all US-based cancer clinical trials averaged more than 6% of all new US cancer cases over this time period, which is more than double the 3% figure the IOM authors cite as the historical average. Considering the slow increase in the number of new US cancer cases per year and the rapid increase in commercially sponsored clinical trials, the observed reduction in enrollment in NCI-sponsored trials might have been unavoidable. Lengthy trial completion times, low trial completion rates, and a shift away from US-based trials would also be likely consequences. For clinical trials of treatments for certain types of cancer, the potentially available participants may be especially scarce. For example, planned enrollment for leukemia trials equaled 12.8% of new US cases from 2005 to 2009. The rate for breast cancer trials equaled 8.9%. As the IOM report authors noted, “publicly funded clinical trials play a vital role by addressing questions that are important to patients but are less likely to be top priorities of industry.” This statement underscores the importance of achieving an optimal mix of publicly and privately funded clinical trials. With the limited number of potential participants in clinical trial in the United States, policy makers will need to consider methods to increase patient participation in cancer clinical trials or, alternatively, ways to allocate enrollment between publicly and privately funded clinical trials with a goal of improving clinical trial completion rates.

Reizdarm: Koloskopieren oder nicht?

Spiegel BMR, Farid M, Esrailian E, Talley J, Chang L. Is irritable bowel syndrome a diagnosis of exclusion? A survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol 2010; 105: 848 – 858 Chey WD, Nojkov B, Rubenstein JH, Dobhan RR, Greenson JK, Cash BD. The yield of colonoscopy in patients with non-constipated irritable bowel syndrome: results from a prospective, controlled US trial. Am J Gastroenterol 2010; 105: 859 – 865

Early Warning: An Ailing Canary in the Mine

Early Warning: An Ailing Canary in the Mine