Optimize clinical trial

Similar results were obtained in the randomized Cancer and Leukemia Group B trial 20 of bisphosphonate-naive patients with breast cancer, prostate cancer, and myeloma in which reduction in the dosing frequency of zoledronic acid from monthly to every 3 months was found to be noninferior.

The clinical relevance of this single time point difference is not clear. Our results differ from the findings in the ZOOM study, 18 which found separation in N-terminal telopeptide between the 2 treatment arms, in favor of the every 4 weeks treatment group, which, however, was not reproduced by our double-blind design.

A feasibility study REFORM of women with metastatic breast cancer involving the bone and prior exposure to intravenous bisphosphonates randomized study participants to receive pamidronate every 3 to 4 weeks or to a deescalated interval of 12 weeks.

Regarding the AEs of special interest, the number of osteonecrosis of the jaw cases, cardiac ischemic AEs, and atrial fibrillation AEs were very low; 2 patients in the every 4 weeks group had an adjudicated osteonecrosis of the jaw event, whereas there were none in the every 12 weeks group.

In the ZOOM study, 18 3 osteonecrosis of the jaw cases were reported in the every 4 weeks group and 4 osteonecrosis of the jaw cases in the every 12 weeks group.

In the current study, no patient in any treatment group experienced an adjudicated atypical femur fracture event, with all femur fractures adjudicated. The proportion of patients who experienced renal treatment-emergent AEs was not obviously different between the 2 treatment groups. As discussed earlier, in the absence of SRE data from the second year of treatment with zoledronic acid vs placebo available at the time this trial was designed, the sample size and noninferiority margin of OPTIMIZE-2 were based on SRE data from the first year of treatment instead.

In addition, the deletion of the placebo arm made it difficult to assess the efficacy of continued treatment with zoledronic acid after the first year. Thus, the results should be interpreted with caution. After discussions with the US Food and Drug Administration, no changes are anticipated in the zoledronic acid label. Further studies are warranted to investigate the effect of long-term treatment with zoledronic acid on bone saturation and bone retention rate as well as clinically relevant outcomes.

Corresponding Author: Gabriel N. Published Online: January 26, Author Contributions: Drs Hortobagyi and Lipton had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Dr Van Poznak reported receiving grants from Novartis Pharmaceuticals Corporation during the conduct of the study and grants from Amgen and Bayer outside the submitted work.

Dr Sauter reported being an employee of Novartis Pharmaceuticals Corporation and holding stock options. Dr Mohanlal reported receiving employment-related salary from Novartis Pharmaceuticals Corporation during the conduct of the study and being employed with Novartis Pharmaceutical Corporation until July , at the time the study was conducted and when the first draft of the manuscript was developed.

Dr Zheng reported being an employee of Novartis Pharmaceuticals Corporation and holding stock options. Dr Lipton reported receiving laboratory grants from Novartis Pharmaceuticals Corporation. No other disclosures were reported.

Additional Contributions : We thank the patients who took part in the trial and the investigators, study nurses, and clinical research associates from the individual trial centers who provided ongoing support.

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Figure 1. Patient Disposition Full Analysis Set. View Large Download. Figure 2. Table 1. Baseline and Demographic Characteristics a.

Table 2. Supplement 1. Trial Protocol. Supplement 2. Additional Details of the Study Methods eMaterial. Additional Details of the Study Results eTable 1. Number of Infusions Before the Study eTable 2. Renal Adverse Events eTable 3. On-treatment Deaths eFigure. Dosing Schedule for a Bone-Modifying Agent. Save Preferences. Privacy Policy Terms of Use. This Issue. Views 10, Citations View Metrics. Twitter Facebook More LinkedIn.

Original Investigation. July Gabriel N. Dakhil, MD 6 ; Barbara B. Hershey Medical Center, Hershey, Pennsylvania. Key Points Question Is zoledronic acid every 12 weeks noninferior to zoledronic acid every 4 weeks?

Study Design and Patients. Randomization and Blinding. Statistical Analysis. Back to top Article Information. Roodman GD. Mechanisms of bone metastasis. N Engl J Med. PubMed Google Scholar Crossref.

Coleman RE. Despite intensive and expensive clinical efforts, its prevalence is growing. Nonpharmacologic treatments are effective at improving pain-related outcomes; however, treatment effect sizes are often modest. Physical therapy PT and cognitive behavioral therapy CBT have the most consistent evidence of effectiveness. Growing evidence also supports mindfulness-based approaches. Discussions with providers and patients highlight the importance of discussing and trying options to find the treatment that works for them and determining what to do when initial treatment is not successful.

Metadata can be stored in various stages of development. It can be updated, approved, and kept as organizational standards. Using a clinical metadata repository MDR results in saved time, a reduced need for resources, and the ability to get quality products to the market quicker. Impact analysis is a key objective of clinical metadata repositories and should be built-in. It lets you see what upstream and downstream metadata and processes are affected if a particular change is made.

Before you make that change. Impact analysis puts you in a much better place to make informed decisions on whether a proposed change is worth making, or not. There should be a way for team members to request changes to existing metadata content. It must be possible to edit, add, and retire metadata content. These changes should go through a well thought out governance process.

See the example below. Governance refers to the process that must be adhered to for any change to existing metadata content and organizational standards.

Or for the creation of new metadata content. A quality clinical metadata repository should allow versioning of internal standards across the organization. It should let you update and improve both study level standards and organizational standards.