Comparison of content of FDA letters not approving applications for new drugs and associated public announcements from sponsors: cross sectional study.

OBJECTIVES: To describe the content of non-public complete response letters issued by the US Food and Drug Administration (FDA) when they do not approve marketing applications from sponsors (drug companies) and to compare them with the content any subsequent press releases issued by those sponsors DESIGN: Cross sectional study. DATA SOURCES: All applications for which FDA's Center for Drug Evaluation and Research initially issued complete response letters (n=61) from 11 August 2008 to 27 June 2013. Complete response letters and press releases were divided into discrete statements related to seven domains and 64 subdomains and assessed to determine whether they matched. RESULTS: 48% (29) of complete response letters cited deficiencies in both the safety and efficacy domains, and only 13% cited neither safety nor efficacy deficiencies. No press release was issued for 18% (11) of complete response letters, and 21% (13) of press releases did not match any statements from the letters. Press release statements matched 93 of the 687 statements (14%), including 16% (30/191) of efficacy and 15% (22/150) of safety statements. Of 32 complete response letters that called for a new clinical trial for safety or efficacy, 59% (19) had matching press release statements. Seven complete response letters reported higher mortality rates in treated participants; only one associated press release mentioned this fact. CONCLUSIONS: FDA generally issued complete response letters to sponsors for multiple substantive reasons, most commonly related to safety and/or efficacy deficiencies. In many cases, press releases were not issued in response to those letters and, when they were, omitted most of the statements in the complete response letters. Press releases are incomplete substitutes for the detailed information contained in complete response letters.

Measurement of attacks and interferences with health care in conflict: validation of an incident reporting tool for attacks on and interferences with health care in eastern Burma.

BACKGROUND: Attacks on health care in armed conflict and other civil disturbances, including those on health workers, health facilities, patients and health transports, represent a critical yet often overlooked violation of human rights and international humanitarian law. Reporting has been limited yet local health workers working on the frontline in conflict are often the victims of chronic abuse and interferences with their care-giving. This paper reports on the validation and revision of an instrument designed to capture incidents via a qualitative and quantitative evaluation method. METHODS: Based on previous research and interviews with experts, investigators developed a 33-question instrument to report on attacks on healthcare. These items would provide information about who, what, where, when, and the impact of each incident of attack on or interference with health. The questions are grouped into 4 domains: health facilities, health workers, patients, and health transports. 38 health workers who work in eastern Burma participated in detailed discussion groups in August 2013 to review the face and content validity of the instrument and then tested the instrument based on two simulated scenarios. Completed forms were graded to test the inter-rater reliability of the instrument. RESULTS: Face and content validity were confirmed with participants expressing that the instrument would assist in better reporting of attacks on health in the setting of eastern Burma where they work. Participants were able to give an accurate account of relevant incidents (86% and 82% on Scenarios 1 and 2 respectively). Item-by-item review of the instrument revealed that greater than 95% of participants completed the correct sections. Errors primarily occurred in quantifying the impact of the incident on patient care. Revisions to the translated instrument based on the results consisted primarily of design improvements and simplification of some numerical fields. CONCLUSION: This instrument was validated for use in eastern Burma and could be used as a model for reporting violence towards health care in other conflict settings.

Local control and long-term disease-free survival for stage D1 (T2-T4N1-N2M0) prostate cancer after radical prostatectomy in the PSA era.

OBJECTIVES: With the advent of prostate-specific antigen (PSA) screening, the number of lymph node metastases found after radical prostatectomy (RP) has been decreasing. Although it has been shown in this population that immediate adjuvant androgen deprivation therapy (ADT) improves survival compared with initiating ADT at clinical recurrence, the effect of starting ADT at biochemical recurrence is unknown. We examined a series of patients with Stage D1 (T2-T4N1-N2M0) prostate cancer discovered after RP, most of whom started ADT at biochemical recurrence. METHODS: A total of 2121 patients underwent RP and bilateral pelvic lymph node dissection from January 1990 and December 2000. Of these men, 28 had lymph node metastases (1.3%), 24 of whom had adequate follow-up data for analysis. RESULTS: No perioperative or long-term complications, such as pelvic recurrence, gross hematuria, urinary retention, or hydronephrosis, developed. With a median follow-up of 74 months, the estimated 5-year survival rate was 94%, similar to the average life expectancy of age-matched men in the United States. The 5-year biochemical disease-free survival rate was 15%. A total of 18 patients who did not start immediate ADT had an estimated 100% overall survival rate at 5 years. CONCLUSIONS: The results of our study have shown that survival for patients with Stage D1 prostate cancer after RP is excellent and equivalent to that of age-matched controls. Long-term pelvic morbidity due to primary tumor progression was prevented by RP. By waiting until PSA failure to initiate ADT, we found that a small percentage of patients (15% at 5 years) were rendered disease free with surgery alone and could avoid the side effects of ADT, with excellent overall survival maintained for those starting ADT at biochemical progression.

Is Hispanic race an important predictor of treatment failure following radical prostatectomy for prostate cancer?

PURPOSE: Hispanic-Americans are the fastest growing minority group in the United States. Many studies have compared prostate cancer treatment outcomes between black and white men, but few such studies have been done with Hispanic men. We compared clinical and pathological features as well as the treatment failure rate of radical prostatectomy in contemporaneously treated groups of Hispanic and white men with prostate cancer. MATERIALS AND METHODS: Between 1995 and 2002, 136 Hispanic men and 315 white men underwent radical prostatectomy. Treatment failure was defined as having a prostate specific antigen (PSA) of 0.2 or greater more than 8 weeks after surgery or receiving any adjuvant therapy. Known predictors of failure and race were evaluated for their ability to predict treatment failure. RESULTS: Median followup was 32 months for Hispanic and 36 months for white patients. Hispanic men were older, had a higher percentage of abnormal rectal examinations, Gleason 7 tumors and preoperative PSA levels greater than 10. Preoperative PSA, specimen Gleason score, pathological stage and surgical margin were all strongly associated with treatment failure (p<0.001). Despite differences in clinical characteristics, overall failure rates did not differ between Hispanic and white men (18.7% vs 17.8%). The odds ratio for treatment failure for Hispanic relative to white men after adjusting for the previously mentioned risk factors was 0.87 (95% CI [0.44, 1.68], p = 0.670). CONCLUSIONS: This study shows that Hispanic race does not influence the treatment failure rate of radical prostatectomy in contemporaneously treated patients with prostate cancer at 1 institution. To our knowledge this study represents the largest of its kind, but longer followup and other confirmatory studies are needed.