Most ASH Abstracts Reporting Phase II Studies Lead to Peer-Reviewed Publications, but Less Than 50% of "Positive" Abstracts Lead to Phase III Investigations: An Analysis of 371 Abstracts 2013 - 2015

Reports of "positive" results in early phase trials as presented at ASH presumably herald therapeutic advances, or at a minimum, a larger, potentially confirmatory, randomized trial. However, the predictive value of an ASH abstract reporting positive results in AML for subsequent clinical utility seems low (Estey 2006, ASH). Furthermore, not all results presented at ASH are published in peer-reviewed journals, and selectively publishing positive results leads to publication bias. Moreover, truly negative studies may be scientifically more rigorous and accurate than positive studies given the unequivocal findings. The extent of publication bias is unknown as is the frequency with which positive or negative abstracts lead to subsequent investigation in phase III and the reasons why positive phase II studies might not progress to phase III. We downloaded all 2013 - 2015 ASH abstracts (N = 17,251) and evaluated all abstracts reporting phase II clinical trials (N = 371) of novel drugs and therapeutic regimens presented at ASH in these years, covering investigational treatments of MM, CLL, AML, DLBCL, MDS, NHL, ALL, CML, MCL, SLL, other lymphomas and POEMS. We first scored abstracts "positive", "negative" or "inconclusive". Criteria for a positive abstract were words/phrases such as "encouraging", "promising", "could represent a novel therapeutic option" and "warrants investigation in a randomized trial". Negative abstracts included terms such as "does not support further research" and "demonstrates no clinical activity". The remainder were scored as inconclusive. Using this approach, we scored 296/371 (80%) abstracts as positive, 37/371 (10%) as negative, and 38/371 (10%) as inconclusive. 292/371 abstracts (79%) were published in peer-reviewed journals. The abstract conclusion (positive, negative or inconclusive) was not associated with publication in a peer-reviewed journal. Most frequently, studies were published in Blood (34/292 [11.6%]) and British Journal of Haematology (39/292 [13.4%]) . In Blood, 91% (31/34) of the studies were positive. British Journal of Haematology published significantly more negative studies than Blood (26%, Fisher Exact p = 0.02). Abstracts reporting studies with larger sample sizes tended to be published more often (p = 0.066). Differences exist between the abstract conclusion and later peer-reviewed publications. Of positive ASH abstracts, 6% changed to a negative conclusion in the peer-reviewed publication. Similarly, 6.5% of the initial negative abstract later reversed to a positive conclusion. 53% of positive abstracts did not lead to phase III studies, as registered on clinicaltrials.gov. Subsequently, regimens described in positive peer-reviewed publications did not proceed to phase III research in 48%. To explore why, we sent questionnaires to the first and/or last authors of positive studies not prompting phase III trials. 52% responded. Failure of positive phase II trials to proceed to phase III was due to the decision by the pharmaceutical company to halt clinical investigation (44%), lack of any intent to study the drug in phase III in the first place (40%), insufficient funding (35%), insufficient efficacy (despite the "positive" abstract; 33%) and safety concerns (4%) (Figure). Additional reasons for not proceeding to phase III were the availability of newer regimens, the rarity of the disease, or when regulatory approval had already been obtained after phase II. In conclusion, "positive" and "negative" ASH abstracts are published as full papers equally often, although the positive ones may be published more often in journals with higher "impact factors". More than half of the regimens presented in positive ASH abstracts remain unevaluated in randomized phase III trials. A separate problem is the likely tendency to disproportionately submit (and/or accept) positive, rather than negative, studies to ASH in the first place. We believe our findings raise issues in clinical research that may not be in the best interest of patients. This demands more consideration than it currently receives. Figure 1 Figure 1. Disclosures Ossenkoppele: Astellas: Consultancy, Honoraria; Agios: Consultancy, Honoraria; Abbvie, AGIOS, BMS/Celgene Astellas,AMGEN, Gilead,Servier,JAZZ,Servier Novartis: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Jazz: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Gilead: Consultancy, Honoraria. Rowe: Biosight Inc.: Consultancy.

Case Study Method: A Step-by-Step Guide for Business Researchers

Qualitative case study methodology enables researchers to conduct an in-depth exploration of intricate phenomena within some specific context. By keeping in mind research students, this article presents a systematic step-by-step guide to conduct a case study in the business discipline. Research students belonging to said discipline face issues in terms of clarity, selection, and operationalization of qualitative case study while doing their final dissertation. These issues often lead to confusion, wastage of valuable time, and wrong decisions that affect the overall outcome of the research. This article presents a checklist comprised of four phases, that is, foundation phase, prefield phase, field phase, and reporting phase. The objective of this article is to provide novice researchers with practical application of this checklist by linking all its four phases with the authors’ experiences and learning from recently conducted in-depth multiple case studies in the organizations of New Zealand. Rather than discussing case study in general, a targeted step-by-step plan with real-time research examples to conduct a case study is given.

STRUKTUR DAN FUNGSI SOSIAL CERITA RAKYAT (LEGENDA SETEMPAT) PINCURAN TUJUAH DI KANAGARIAN SIKUCUA TIMUR KECAMATAN V KOTO KAMPUANG DALAM KABUPATEN PADANG PARIAMAN

This study aims to describe: (1) folklore structure of local legend Tujuah in Kanagarian Sikucua Timur sub-district V Koto Kampuang Dalam Padang Pariaman district, (2) social function folklore local legend Tujuah in Kanagarian Sikucua Timur sub-district V district Koto Kampuang sub-district Padang Pariaman. This type of research is qualitative research using descriptive methods. The data of this research are folklore of local legends of Tujuah in Kanagarian Sikucua Timur, Subdistrict V, Koto Kampuang Dalam, Padang Pariaman District. The data in this study were analyzed in four stages, namely: (1) the data identification stage, the data collected from the informants were identified through two stages, namely: (a) the stage of transcription, transliteration, and (b) the stage of describing the results of observation, recording, and interview, (2) Data classification or analysis stage, (3) Discussion phase and conclusion of the results of classification or data analysis, (4) Reporting phase. Based on the results of the study, it can be concluded that the folklore structure of local legend Tujuah in Kanagarian Sikucua Timur, V Subdistrict, Koto Kampuang Dalam, Padang Pariaman Regency consists of, namely: (1) language style, language style speech used by folklore in local legend Folklore Pariaman dialect, (2) point of view, (3) character and character, figures found in local folklore local legend Pujuran Tujuah is divided into two, Sutan Bagindo as the main character, and Putri Bungsu, Mandeh Rubiah, Rajo Simanta as a side character, ( 4) background, background of folklore local legend Pujuran Tujuah is a setting, time setting and social setting, (5) plot / plot, plot / plot in folklore local legend Pincuran Tujuah is a conventional plot, and has three stages: , the initial stage or introduction (beginning), middle stage or conflict (midle), and the final stage or end (end), (6) themes, and (7) mandate. The social function of folklore local legend of the Tujuah Swamp in Kanagarian Sikucua Timur, V Koto Kampuang Dalam District, Padang Pariaman Regency, namely: (1) educating, and (2) entertaining.Keywords: folklore, legend, minangkabau

Toward harmonization of clinical molecular diagnostic reports: findings of an international survey

Background: The International Organization for Standardization (ISO) 15189 standard provides recommendations for the postexamination reporting phase to enhance quality in clinical laboratories. The purpose of this study was to encourage a broad discussion on current reporting practices for molecular diagnostic tests by conducting a global survey of such practices. Methods: The International Federation of Clinical Chemistry and Laboratory Medicine’s Committee for Molecular Diagnostics (IFCC C-MD) surveyed laboratories on selected ISO 15189 recommendations and topics. The survey addressed the following aspects: (1) laboratory demographics, (2) report format, (3) result reporting/layout, (4) comments in report and (5) interpretation and clinical decision-making information. Additionally, participants indicated categories needing standardization. Results: Sixteen responses from laboratories located in Asia, Europe, the Middle East, North America and South America were received. Several categories yielded 100% agreement between laboratories, whereas other categories had less than or equal to 50% concordance. Participants scored “nomenclature” and “description of methodologies” as the two most frequently cited aspects needing standardization. Conclusions: The postexamination phase requires extensive and consistent communication between the laboratory, the healthcare provider and the end user. Surveyed laboratories were most likely to follow explicit ISO 15189 recommendations vs. recommendations when the term(s) “where appropriate or where applicable” was used. Interpretation and reporting of critical values varied among participants. Although the outcome of this study may not fully represent the practices of all molecular testing laboratories in countries around the world, the survey identified and specified several recommendations that are requirements for harmonized reporting in molecular diagnostics.

Medical laboratory associated errors: the 33-month experience of an on-line volunteer Canadian province wide error reporting system

Background:This article reports on the findings of 12,278 laboratory related safety events that were reported through the British Columbia Patient Safety & Learning System Incident Reporting System.Methods:The reports were collected from 75 hospital-based laboratories over a 33-month period and represent approximately 4.9% of all incidents reported.Results:Consistent with previous studies 76% of reported incidents occurred during the pre-analytic phase of the laboratory cycle, with twice as many associated with collection problems as with clerical problems. Eighteen percent of incidents occurred during the post-analytic reporting phase. The remaining 6% of reported incidents occurred during the actual analytic phase. Examination of the results suggests substantial under-reporting in both the post-analytic and analytic phases. Of the reported events, 95.9% were reported as being associated with little or no harm, but 0.44% (55 events) were reported as having severe consequences.Conclusions:It is concluded that jurisdictional reporting systems can provide valuable information, but more work needs to be done to encourage more complete reporting of events.

POLA FRAUD PADA PENYELENGARAAN BIMBINGAN TEKNIS (BIMTEK) DI SEKTOR PEMERINTAHAN

<p class="Default"><em>This study is aims to determine patterns of fraud in the technical assistance implementation activities in the government sector that is in the local work unit in the district X. It’s descriptive qualitative study by interviewing several informants who where directly involved in the technical assistance.The aspects that will be analyzed include three phases: planning phases, implementation phases and reporting phase. The result of this study shows that the frauds in the three phase of technical assistance implementation. There are mark up of the price and number of participants at the planning phase. In the implementation phase the fraud is within shortening timing and eventually there is technical assistance fictitious, and at the reporting phase found that the fraud pattern is a discrepancy between the letter of accountability with real cost.</em></p>

Zuiver belevingsonderzoek: het vermijden van onbedoelde beïnvloeding in kwalitatief onderzoek

Modelling Shared Reality Modelling Shared Reality This article introduces ‘Modelling Shared Reality’, a new qualitative research methodology which has its roots in Clean Language and Symbolic Modelling. Using the protocol explained in this article, undesired influence of the researcher is minimized during all phases of the research: the interviews, the analysis and the reporting phase. The methodology is action-oriented: both the process and the results function as a catalyst for actions or behavioral change. It is frequently used in the context of organizational change or development processes, as well as policy decisions, policy evaluations, and participative processes.