Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients’ symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item’s importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

PurposeThe purpose of the paper is to provide a thorough analysis of the concepts of business intelligence (BI), knowledge management (KM) and analytical CRM (aCRM) and to establish a framework for integrating all the three to each other. The paper also seeks to establish a KM and aCRM based framework using data mining (DM) techniques, which helps in the enterprise decision‐making. The objective is to share how KM and aCRM can be integrated into this seamless analytics framework to sustain excellence in decision making using effective data mining techniques and to explore how working on such aCRM system can be effective for enabling organizations delivering complete solutions.Design/methodology/approachThis paper is based on focused and dedicated study of the literature present on the aCRM, KM and data mining techniques. The paper considered how to develop a strategy and operational framework that would build aCRM on the foundation of existing DM techniques and KM approach to meet the business challenges. Based on this research, a customized, integrated framework, to match the needs of business was designed.FindingsKM focuses on managing knowledge within the organization and aCRM focuses on gaining analytical information from the customer data. Both KM and aCRM help in the decision making process and understanding. This knowledge is difficult to uncover. Hence, this paper explains the importance of data mining tools and techniques to uncover knowledge by the integration between KM and aCRM. This paper presents an integrated KM and aCRM based framework using DM techniques.Research limitations/implicationsAll the firms may not be in favor of adopting KM while implementing aCRM. The KM requires a convalesce of organizational culture, technology innovations, effective work force in culminating knowledge dissemination in all business domains.Practical implicationsThe organizations implementing this knowledge enabled aCRM framework would be easily able to convert their business knowledge via the analytical CRM to solve many business issues, such as increase response rates from direct mail, telephone, e‐mail, and internet delivered marketing campaigns, increased sales and increased services. With aCRM, firms can identify their most profitable customers and use this knowledge for promotional schemes for those customers as well as identify future customers with prediction on ROI.Originality/valueThe need for the integration of KM and aCRM is clear. It is written for practitioners who are looking for approaches to improve business performance and maintain high profits for their business by incorporating knowledge‐enabled aCRM in their setup.

Multiple myeloma is mostly an incurable disease. The U.S. Food and Drug Administration (FDA) granted daratumumab accelerated approval in November 2015 as monotherapy for patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or who are double refractory to a proteasome and an immunomodulatory agent. This article describes the FDA review of the strength of evidence for this application and its clinical implications for the multiple myeloma population.

Swarm intelligence (SI) is the collective behavior of decentralized, self-organized systems, natural or artificial. SI systems are typically made up of a population of simple agents interacting locally with one another and with their environment. The inspiration often comes from nature, especially biological systems. The agents follow very simple rules, and although there is no centralized control structure dictating how individual agents should behave, local, and to a certain degree random, interactions between such agents lead to the emergence of "intelligent" global behavior, unknown to the individual agents. Natural examples of SI include ant colonies, bird flocking, animal herding, bacterial growth, and fish schooling. Research in SI started in the late 1980s. Besides the applications to conventional optimization problems, SI can be employed in library materials acquisition, communications, medical dataset classification, dynamic control, heating system planning, moving objects tracking, and prediction. Indeed, SI can be applied to a variety of fields in fundamental research, engineering, industries, and social sciences. The main objective of this special issue is to provide the readers with a collection of high quality research articles that address the broad challenges in application aspects of swarm intelligence and reflect the emerging trends in state-of-the-art algorithms. The special issue received 42 high quality submissions from different countries all over the world. All submitted papers followed the same standard (peer-reviewed by at least three independent reviewers) as applied to regular submissions to "this journal". Due to the limited space, 15 papers

Background: Racial disparity in the incidence of multiple myeloma is well established; however, to the authors' knowledge, little is known regarding the impact of racial differences on disease characteristics, response to therapy, and clinical outcome. Methods: The authors studied 453 patients (174 of whom were black and 279 of whom were white) who underwent transplant between 2000 and 2013. The median follow-up was 4.4 years. Results: Black patients were significantly younger than white patients (median age, 54 years vs 59 years; P<.0001), more frequently presented with anemia (P 5 .04), had more of the immunoglobulin G isotype (P<.001), and had a borderline favorable cytogenetic risk (P 5 .06). Overall response to induction was similar, but deeper responses were observed in more white patients compared with black patients receiving immunomodulatory drug-based induction (P 5 .02). Referral for transplant was significantly delayed in black individuals (median, 1.3 years vs 0.9 years; P 5 .003). Overall survival from the time of transplant was similar for black and white patients, with medians of 6.2 years and 5.7 years, respectively, but survival from the time of diagnosis was significantly longer among black individuals (median, 7.7 years vs 6.1 years; P 5 .03). Maintenance therapy was found to positively impact progression-free survival but not overall survival, irrespective of race. Conclusions: The results of the current study confirm ethnic differences in age, referral patterns, response to therapy, and overall survival. Future validation of these disparities is urgently needed.

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma–related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51–79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit–risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.

IMPORTANCE Patient-reported outcomes (PROs) can inform health care decisions, regulatory decisions, and health care policy. They also can be used for audit/benchmarking and monitoring symptoms to provide timely care tailored to individual needs. However, several ethical issues have been raised in relation to PRO use. OBJECTIVE To develop international, consensus-based, PRO-specific ethical guidelines for clinical research. EVIDENCE REVIEWThe PRO ethics guidelines were developed following the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network's guideline development framework. This included a systematic review of the ethical implications of PROs in clinical research. The databases MEDLINE (Ovid), Embase, AMED, and CINAHL were searched from inception until March 2020. The keywords patient reported outcome* and ethic* were used to search the databases. Two reviewers independently conducted title and abstract screening before full-text screening to determine eligibility. The review was supplemented by the SPIRIT-PRO Extension recommendations for trial protocol. Subsequently, a 2-round international Delphi process (n = 96 participants; May and August 2021) and a consensus meeting (n = 25 international participants; October 2021) were held. Prior to voting, consensus meeting participants were provided with a summary of the Delphi process results and information on whether the items aligned with existing ethical guidance.FINDINGS Twenty-three items were considered in the first round of the Delphi process: 6 relevant candidate items from the systematic review and 17 additional items drawn from the SPIRIT-PRO Extension. Ninety-six international participants voted on the relevant importance of each item for inclusion in ethical guidelines and 12 additional items were recommended for inclusion in round 2 of the Delphi (35 items in total). Fourteen items were recommended for inclusion at the consensus meeting (n = 25 participants). The final wording of the PRO ethical guidelines was agreed on by consensus meeting participants with input from 6 additional individuals. Included items focused on PRO-specific ethical issues relating to research rationale, objectives, eligibility requirements, PRO concepts and domains, PRO assessment schedules, sample size, PRO data monitoring, barriers to PRO completion, participant acceptability and burden, administration of PRO questionnaires for participants who are unable to self-report PRO data, input on PRO strategy by patient partners or members of the public, avoiding missing data, and dissemination plans. CONCLUSIONS AND RELEVANCEThe PRO ethics guidelines provide recommendations for ethical issues that should be addressed in PRO clinical research. Addressing ethical issues of PRO clinical research has the potential to ensure high-quality PRO data while minimizing participant risk, burden, and harm and protecting participant and researcher welfare.

On June 29, 2020, the FDA approved pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection (Phesgo) for the treatment of patients with HER2-positive early-stage and metastatic breast cancer. Patients should be selected for therapy based on an FDA-approved companion diagnostic test. Approval was primarily based on the FeDeriCa trial, a randomized, open-label, multicenter comparability study of pertuzumab, trastuzumab, and hyaluronidase-zzxf subcutaneous injection compared with intravenous pertuzumab and intravenous trastuzumab administered in the neoadjuvant and adjuvant settings with chemotherapy for the treatment of patients with early breast cancer. The pharmacokinetic endpoints were, first, to demonstrate that the exposure of subcutaneous pertuzumab was not inferior to that of intravenous pertuzumab, and then to demonstrate that the exposure of subcutaneous trastuzumab was not inferior to that of intravenous trastuzumab. The primary endpoints were met with the observed lower limit of the two-sided 90% confidence intervals above the prespecified noninferiority margins. The most common adverse reactions were alopecia, nausea, diarrhea, anemia, and asthenia. The totality of the evidence demonstrated comparability of the subcutaneous product to intravenous, allowing for extrapolation and approval of all breast cancer indications for which intravenous trastuzumab and pertuzumab are approved.