Good Publication Practice Guidelines Research Articles

An Overview of the 2022 Update of Good Publication Practice (GPP) Guidelines: A Medical Writer’s Perspective

The Good Publication Practice (GPP) guidelines are a set of principles and recommendations pertaining to peer-reviewed or peer-orientated publications arising from research funded by or conducted in collaboration with industry sponsors, typically pharmaceutical, biotechnology, and medical device companies.
 This year marks the 20-year anniversary of the first GPP guidelines, which were published in 2003.1 These initial GPP guidelines were developed to promote transparency and to establish standards for publication practice used by pharmaceutical companies. Since then, GPP guidelines have undergone several updates to reflect changes within the publication field and to provide additional practical guidance on publication processes and procedures. These updates include GPP22 published in 2009 and GPP33 published in 2013. Good Practice for Conference Abstracts and Presentations (GPCAP)4 was published in 2019 to provide guidance specifically for congress abstract and presentations. The latest update of the GPP guidelines, the GPP 2022 update, was published in August 20225.

Good Publication Practice (GPP) Guidelines for Company-Sponsored Biomedical Research: 2022 Update.

These updated Good Publication Practice (GPP) guidelines include recommendations for publishing company-sponsored biomedical research. The GPP guidelines apply to peer-reviewed or peer-oriented biomedical publications, such as manuscripts, meeting presentations, posters, and abstracts, as well as enhanced content, such as plain-language summaries. The current GPP guidelines incorporate guidance on ethics and transparency as well as the planning, development, review, and approval of biomedical publications and policies and procedures that describe these practices. Supplemental materials lay out processes for steering committees, publication plans, publication working groups, determining authorship, and documentation. Information about new topics, such as alliances and working with patients, has been included where appropriate within these supplemental materials. Incorporating the principles and best practices presented in these GPP guidelines will result in increased transparency and a firm ethical footing. This guidance is also intended to enable the compliant incorporation of new and emerging publication tools for the ethical publication of company-sponsored research.

A case of normal C1 esterase inhibitor hereditary angioedema successfully treated with berotralstat

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, recurrent, localized episodes of swelling that often affect the extremities, face, abdomen, and larynx.1Busse PJ Christiansen SC Riedl MA Banerji A Bernstein JA Castaldo AJ et al.US HAEA medical advisory board 2020 guidelines for the management of hereditary angioedema.J Allergy Clin Immunol Pract. 2021; 9 (e3): 132-150Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar,2Caballero T. Treatment of hereditary angioedema.J Investig Allergol Clin Immunol. 2021; 31: 1-16Crossref PubMed Scopus (12) Google Scholar HAE is most typically caused by mutations in the C1-esterase inhibitor (C1-INH) gene (serpin family G member 1; SERPING1) that result in deficient (type 1) or dysfunctional (type 2) C1-INH protein.3Longhurst HJ Bork K. Hereditary angioedema: an update on causes, manifestations and treatment.Br J Hosp Med. 2019; 80: 391-398Crossref PubMed Scopus (41) Google Scholar These mutations lead to dysregulation of the kallikrein-bradykinin cascade and increases in bradykinin production and vascular permeability, which are thought to be the main causes of HAE attacks.4Banday AZ Kaur A Jindal AK Rawat A Singh S. An update on the genetics and pathogenesis of hereditary angioedema.Genes Dis. 2019; 7: 75-83Crossref PubMed Scopus (32) Google Scholar Type 1 and type 2 HAE, which are collectively known as HAE-C1-INH, are associated with lower-than-normal plasma levels of both complement component 4 (C4) and C1-INH functionality in laboratory tests and represent 95% of HAE cases.3Longhurst HJ Bork K. Hereditary angioedema: an update on causes, manifestations and treatment.Br J Hosp Med. 2019; 80: 391-398Crossref PubMed Scopus (41) Google Scholar,4Banday AZ Kaur A Jindal AK Rawat A Singh S. An update on the genetics and pathogenesis of hereditary angioedema.Genes Dis. 2019; 7: 75-83Crossref PubMed Scopus (32) Google Scholar However, some patients present with a form of HAE that is typically associated with normal plasma C1-INH levels and functionality (HAE-nl-C1-INH), normal plasma C4 complement levels, and attacks that are predominately facial in nature.3Longhurst HJ Bork K. Hereditary angioedema: an update on causes, manifestations and treatment.Br J Hosp Med. 2019; 80: 391-398Crossref PubMed Scopus (41) Google Scholar Diagnosis of HAE-nl-C1-INH represents a considerable challenge and is reliant on genetic testing.3Longhurst HJ Bork K. Hereditary angioedema: an update on causes, manifestations and treatment.Br J Hosp Med. 2019; 80: 391-398Crossref PubMed Scopus (41) Google Scholar,5Henao MP Kraschnewski JL Kelbel T Craig TJ. Diagnosis and screening of patients with hereditary angioedema in primary care.Ther Clin Risk Manag. 2016; 12: 701-711Crossref PubMed Scopus (42) Google Scholar Current evidence suggests that, similar with HAE-C1-INH, HAE-nl-C1-INH is mediated by increased bradykinin production.3Longhurst HJ Bork K. Hereditary angioedema: an update on causes, manifestations and treatment.Br J Hosp Med. 2019; 80: 391-398Crossref PubMed Scopus (41) Google Scholar,6Bork K. Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor.Allergy Asthma Clin Immunol. 2010; 6: 15Crossref PubMed Google Scholar Consistent with this, mutations in genes involved in bradykinin formation, such as factor XII, plasminogen, angiopoietin-1, kininogen-1, and myoferlin genes, have been identified in patients with HAE-nl-C1-INH.7Bork K Machnig T Wulff K Witzke G Prusty S Hardt J. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence.Orphanet J Rare Dis. 2020; 15: 289Crossref PubMed Scopus (39) Google Scholar However, the genetic basis of HAE-nl-C1-INH is still unknown in many cases,7Bork K Machnig T Wulff K Witzke G Prusty S Hardt J. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence.Orphanet J Rare Dis. 2020; 15: 289Crossref PubMed Scopus (39) Google Scholar which, in combination with the lack of an available confirmatory biomarker or diagnostic test,1Busse PJ Christiansen SC Riedl MA Banerji A Bernstein JA Castaldo AJ et al.US HAEA medical advisory board 2020 guidelines for the management of hereditary angioedema.J Allergy Clin Immunol Pract. 2021; 9 (e3): 132-150Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar can make it difficult for patients to access insurance coverage for their treatment. Therefore, physicians of patients with suspected HAE-nl-C1-INH may choose to initiate a trial course of an HAE-specific therapy to observe a treatment response,8Riedl MA Banerji A Gower R. Current medical management of hereditary angioedema: follow-up survey of US physicians.Ann Allergy Asthma Immunol. 2021; 126: 264-272Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar which can provide a rationale for insurance coverage of long-term treatment costs. Here, we report a case of HAE-nl-C1-INH occurring in the context of a family history of HAE-C1-INH (type 1) disease, which was difficult to treat because of the patient's needle phobia, but ultimately responded well to oral berotralstat therapy. The patient was a 60-year-old woman who reported several previous episodes of swelling that came on over the course of a day and were atypically limited mostly to her hands, feet, breasts, or abdomen. The patient reported that these painful swelling episodes occurred at a frequency of 2 to 3 times a month and typically lasted 2 to 4 days, during which she struggled to go about her usual daily activities. Before undergoing a total hysterectomy in her 40s, the patient had also experienced severe abdominal pain and swelling during her menstrual cycle, occasionally including genital involvement. The patient's mother, sister, cousin, and daughter experienced similar symptoms, and her daughter had received a diagnosis of laboratory-supported HAE-C1-INH (type 1). Therefore, the patient's family history and presenting symptoms led to a suspicion of undiagnosed HAE. During laboratory assessments for HAE in August 2020, the patient had normal serum levels of C1-INH antigen (21 mg/dL), C1-INH functionality that was 90% of normal, and normal serum levels of C4 complement (30 mg/dL). These values remained at normal levels when measured during 2 swelling attacks and the patient also had normal tryptase levels during attacks. These clinical findings indicated that the patient likely had HAE-nl-C1-INH despite having a family history of HAE-C1-INH (type 1). Analysis of the patient's SERPING1 gene using the GeneDx HAE-C1-INH (type 1 and type 2) panel (GeneDx, Gaithersburg, Maryland) did not identify any reportable variants, consistent with HAE-nl-C1-INH. The patient declined additional genetic testing because of cost. A review of the patient's medical history indicated that previous use of antihistamines (cetirizine and diphenhydramine), hydroxychloroquine for rheumatoid arthritis, and steroids for asthma did not noticeably affect her swelling attacks. However, the patient reported (and documented with photographs) that the use of recombinant C1-INH replacement therapy (conestat alfa) had resolved swelling attacks within an hour of administration on 2 separate occasions before our involvement. Her positive response to recombinant C1-INH replacement therapy was supportive of an HAE diagnosis and consistent with the successful treatment of HAE-nl-C1-INH attacks with C1-INH concentrate and icatibant reported in the literature.7Bork K Machnig T Wulff K Witzke G Prusty S Hardt J. Clinical features of genetically characterized types of hereditary angioedema with normal C1 inhibitor: a systematic review of qualitative evidence.Orphanet J Rare Dis. 2020; 15: 289Crossref PubMed Scopus (39) Google Scholar At the time of the patient's presentation, typically prescribed HAE-specific prophylactics included intravenous and subcutaneous treatments.2Caballero T. Treatment of hereditary angioedema.J Investig Allergol Clin Immunol. 2021; 31: 1-16Crossref PubMed Scopus (12) Google Scholar Therefore, we initially prescribed the patient lanadelumab prophylaxis (300 mg) every 2 weeks and icatibant (30 mg) on demand. However, because of severe needle phobia, the patient declined treatment with lanadelumab or icatibant. Therefore, documentation of treatment response to standard HAE therapeutics could not initially be obtained for this patient, causing considerable challenges in acquiring long-term insurance coverage for treatment. From the fall of 2020 through February 2021, the patient continued to have 2 to 3 swelling attacks per month. During this time, we were able to offer the patient oral treatment with berotralstat, a plasma kallikrein inhibitor that was approved as a once-daily prophylactic therapy to prevent HAE attacks in patients 12 years and older by the Food and Drug Administration in December 2020.9US Food and Drug Administration. ORLADEYO (berotralstat) capsules, for oral use. 2020. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/214094s000lbl.pdf. Accessed September 14, 2021.Google Scholar During the first 2 to 3 weeks of berotralstat therapy, the patient reported experiencing mild to moderate upset stomach and diarrhea, which were self-resolving and managed by taking the medication with food. Follow-up of the patient after 6 months of berotralstat treatment indicated that her HAE was well-controlled with no breakthrough swelling attacks since starting berotralstat. The patient also reported a noticeable improvement in her anxiety levels because berotralstat prophylaxis reassured her that she would be much less likely to need injectable medication for on-demand or abortive HAE therapy. On the basis of our findings, berotralstat may benefit other patients with HAE-nl-C1-INH and needle phobia. Medical writing support was provided by Jennifer Shepherd, PhD, Porterhouse Medical Group and funded by BioCryst Pharmaceuticals, Inc, Durham, North Carolina, United States, in accordance with good publication practice guidelines.

Effectiveness of Sodium Zirconium Cyclosilicate in Hemodialysis Patients With Severe Hyperkalemia

Severe hyperkalemia is often defined as predialysis serum potassium (sK+) concentration ≥6.0 mmol/l and is associated with a greater risk of hospitalization, major adverse cardiovascular events, and all-cause mortality versus referent predialysis sK+ concentrations.1Einhorn L.M. Zhan M. Hsu V.D. et al.The frequency of hyperkalemia and its significance in chronic kidney disease.Arch Intern Med. 2009; 169: 1156-1162https://doi.org/10.1001/archinternmed.2009.132Crossref PubMed Scopus (397) Google Scholar,2Karaboyas A. Zee J. Brunelli S.M. et al.Dialysate potassium, serum potassium, mortality, and arrhythmia events in hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2017; 69: 266-277https://doi.org/10.1053/j.ajkd.2016.09.015Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Several approaches are available for managing potassium homeostasis in hemodialysis patients.3Pun P.H. Middleton J.P. Dialysate potassium, dialysate magnesium, and hemodialysis risk.J Am Soc Nephrol. 2017; 28: 3441-3451https://doi.org/10.1681/ASN.2017060640Crossref PubMed Scopus (32) Google Scholar A challenge in selecting an appropriate dialysate potassium concentration is balancing removal of potassium to avoid hyperkalemia while minimizing the risk of adverse events associated with lowering potassium too rapidly. The use of nondialytic measures, such as potassium binders during the interdialytic period, to improve potassium homeostasis decreases the need to expose patients to a dialysate with low potassium concentrations.3Pun P.H. Middleton J.P. Dialysate potassium, dialysate magnesium, and hemodialysis risk.J Am Soc Nephrol. 2017; 28: 3441-3451https://doi.org/10.1681/ASN.2017060640Crossref PubMed Scopus (32) Google Scholar Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder that preferentially captures potassium in the gastrointestinal lumen, increasing potassium fecal excretion and thereby reducing sK+ concentration.4Stavros F. Yang A. Leon A. Nuttall M. Rasmussen H.S. Characterization of structure and function of ZS-9, a K+ selective ion trap.PLoS One. 2014; 9e114686https://doi.org/10.1371/journal.pone.0114686Crossref PubMed Scopus (97) Google Scholar,5Kosiborod M. Rasmussen H.S. Lavin P. et al.Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial.JAMA. 2014; 312: 2223-2233Crossref PubMed Scopus (228) Google Scholar The phase IIIb DIALIZE study (NCT03303521) revealed that SZC is an effective and well-tolerated treatment for hyperkalemia in patients with end-stage kidney disease undergoing maintenance hemodialysis.6Fishbane S. Ford M. Fukagawa M. et al.A phase 3b, randomized, double-blind, placebo-controlled study of sodium zirconium cyclosilicate for reducing the incidence of predialysis hyperkalemia.J Am Soc Nephrol. 2019; 30: 1723-1733https://doi.org/10.1681/ASN.2019050450Crossref PubMed Scopus (52) Google Scholar Here, we report the results of a post hoc analysis of DIALIZE that assessed the efficacy of SZC versus placebo in patients with severe hyperkalemia (predialysis sK+ concentration ≥6.0 mmol/l) at baseline. In DIALIZE, at baseline (visit 1, day −7), 88 patients (SZC n = 46, placebo n = 42) had predialysis sK+ concentration ≥6.0 mmol/l and 106 patients (SZC n = 49, placebo n = 57) had predialysis sK+ concentration <6.0 mmol/l (Supplementary Results and Supplementary Table S1). Treatment responders were defined as patients who, during the 4-week evaluation period, maintained target predialysis sK+ concentration for ≥3 of 4 hemodialysis treatments after the long interdialytic interval (LIDI) and did not require rescue therapy to lower sK+ concentration. Among patients with baseline severe hyperkalemia, the proportions of treatment responders were significantly greater with SZC versus placebo using target predialysis sK+ ranges of 4.0 to 5.0 mmol/l (34.8% vs. 0%, respectively; Figure 1a) and an extended range of 4.0 to 5.5 mmol/l (67.4% vs. 19.0%, respectively; Figure 1b) (both P < 0.0001 for SZC vs. placebo). For patients receiving SZC, there was no statistical difference between baseline predialysis sK+ ≥6.0 mmol/l versus <6.0 mmol/l subgroups in responder rates using a target predialysis sK+ range of 4.0 to 5.0 mmol/l (34.8% vs. 46.9%, respectively; P = 0.2974) and an extended range of 4.0 to 5.5 mmol/l (67.4% vs. 71.4%, respectively; P = 0.8239). In the baseline severe hyperkalemia subgroup, the proportions of patients achieving target predialysis sK+ ranges at ≥1, ≥2, ≥3, and 4 LIDI visits in the 4-week evaluation period were greater with SZC versus placebo at both target predialysis sK+ ranges (Figure 2a and b ). In the baseline severe hyperkalemia subgroup, 17.4% and 47.8% of patients receiving SZC achieved target predialysis sK+ ranges of 4.0 to 5.0 mmol/l and 4.0 to 5.5 mmol/l at all 4 LIDI visits, respectively, versus 0% and 2.4% of patients receiving placebo, respectively (Figure 2a and b). Logistic regression analysis indicated that differences in the proportions of patients achieving target predialysis sK+ ranges at ≥1, ≥2, ≥3, and 4 LIDI visits were significant for SZC versus placebo, based on 95% CIs not crossing 0% (Figure 2a and b).Figure 2Proportions of patients with target predialysis sK+ range of (a) 4.0 to 5.0 mmol/l and (b) 4.0 to 5.5 mmol/l at ≥1, ≥2, ≥3, and 4 LIDI visits and corresponding mean sK+ concentrations, by baseline predialysis sK+ subgroup. Visit 1 (day −7) predialysis sK+ measurement was used as baseline. Only sK+ data from LIDI visits during the evaluation period (days 36, 43, 50, and 57) were used. Patients who received rescue therapy were included. Percentages were calculated for each treatment arm using the number of patients in each predialysis sK+ subgroup at baseline as the denominator; no imputation of missing data was conducted. sK+ concentrations are overall mean (SD) for patients with target predialysis sK+ range at ≥1, ≥2, ≥3, or 4 LIDI visits. LIDI, long interdialytic interval; sK+, serum potassium; SZC, sodium zirconium cyclosilicate.View Large Image Figure ViewerDownload Hi-res image Download (PPT) With both SZC and placebo, mean predialysis sK+ concentrations over the LIDI visits in the 4-week evaluation period were numerically greater for patients with baseline predialysis sK+ ≥6.0 mmol/l than those with <6.0 mmol/l. Mean predialysis sK+ concentrations were consistently and significantly lower with SZC versus placebo in both baseline predialysis sK+ subgroups (P < 0.0001 for SZC versus placebo at each LIDI visit) (Supplementary Figure S1). The frequency of predialysis hypokalemia (sK+ <3.5 mmol/l) was low overall (Supplementary Table S3). The proportions of patients with hypokalemia were numerically higher with SZC in the baseline predialysis sK+ <6.0 mmol/l subgroup than ≥6.0 mmol/l subgroup (Supplementary Table S3). To the best of our knowledge, this is the first assessment of the efficacy of a potassium binder in maintenance hemodialysis patients with severe hyperkalemia (predialysis sK+ concentration ≥6.0 mmol/l) based on data from a randomized controlled trial. Among the patients with severe hyperkalemia, the rates of treatment response were significantly greater with SZC versus placebo, regardless of target predialysis sK+ range used (i.e., 4.0–5.0 mmol/l or 4.0–5.5 mmol/l). Among the patients receiving placebo with severe hyperkalemia, mean predialysis sK+ concentrations over 4 weeks remained at approximately 6.0 mmol/l, indicating without additional strategies these patients continued to be at risk of persistent severe hyperkalemia and associated adverse events.1Einhorn L.M. Zhan M. Hsu V.D. et al.The frequency of hyperkalemia and its significance in chronic kidney disease.Arch Intern Med. 2009; 169: 1156-1162https://doi.org/10.1001/archinternmed.2009.132Crossref PubMed Scopus (397) Google Scholar,2Karaboyas A. Zee J. Brunelli S.M. et al.Dialysate potassium, serum potassium, mortality, and arrhythmia events in hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2017; 69: 266-277https://doi.org/10.1053/j.ajkd.2016.09.015Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar Among SZC-treated patients, the extended predialysis sK+ range of 4.0 to 5.5 mmol/l reduced the impact of severe hyperkalemia on the efficacy outcomes evaluated. Findings from the treatment responder analysis indicate that some SZC-treated patients had reductions from baseline in predialysis sK+ concentration but were not deemed as responders using the target predialysis sK+ range of 4.0 to 5.0 mmol/l because their sK+ concentration was between 5.0 mmol/l and 5.5 mmol/l. Nevertheless, the extended predialysis sK+ range of 4.0 to 5.5 mmol/l reflects one deemed to be acceptable in clinical practice, while avoiding concentrations >5.5 mmol/l associated with increased hospitalization and mortality.2Karaboyas A. Zee J. Brunelli S.M. et al.Dialysate potassium, serum potassium, mortality, and arrhythmia events in hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2017; 69: 266-277https://doi.org/10.1053/j.ajkd.2016.09.015Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar These findings suggest that, among hemodialysis patients with severe hyperkalemia, SZC lowers and maintains predialysis sK+ concentrations to a clinically acceptable range in most patients over 4 weeks. The frequency of predialysis hypokalemia events was low overall and generally comparable for SZC and placebo. The events of postdialysis hypokalemia were numerically greater with SZC versus placebo, and among the baseline predialysis sK+ <6.0 mmol/l versus ≥6.0 mmol/l subgroups, consistent with the potassium-lowering effects of SZC in addition to hemodialysis and the smaller reduction in sK+ required to meet the hypokalemia threshold, respectively. A challenging aspect of hyperkalemia management is the lack of a standardized definition for the grading of severity.7Alfonzo A. Harrison A. Baines R. Chu A. Mann S. MacRury M. Clinical practice guidelines: treatment of acute hyperkalaemia in adults. The Renal Association.https://ukkidney.org/sites/renal.org/files/RENAL%20ASSOCIATION%20HYPERKALAEMIA%20GUIDELINE%202020.pdfGoogle Scholar,8Clase C.M. Carrero J.J. Ellison D.H. et al.Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference.Kidney Int. 2020; 97: 42-61https://doi.org/10.1016/j.kint.2019.09.018Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar Collectively, there is consensus to immediately assess and treat patients with severe hyperkalemia.7Alfonzo A. Harrison A. Baines R. Chu A. Mann S. MacRury M. Clinical practice guidelines: treatment of acute hyperkalaemia in adults. The Renal Association.https://ukkidney.org/sites/renal.org/files/RENAL%20ASSOCIATION%20HYPERKALAEMIA%20GUIDELINE%202020.pdfGoogle Scholar,8Clase C.M. Carrero J.J. Ellison D.H. et al.Potassium homeostasis and management of dyskalemia in kidney diseases: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference.Kidney Int. 2020; 97: 42-61https://doi.org/10.1016/j.kint.2019.09.018Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar The recent Renal Association Clinical Practice Guidelines on Hemodialysis recommend maintaining a predialysis sK+ concentration range of 4.0 to 6.0 mmol/l,9Ashby D. Borman N. Burton J. et al.Renal Association clinical practice guideline on haemodialysis.BMC Nephrol. 2019; 20: 379https://doi.org/10.1186/s12882-019-1527-3Crossref PubMed Scopus (46) Google Scholar as a sK+ concentration ≥6.0 mmol/l is associated with a greater risk of hospitalization and all-cause mortality.1Einhorn L.M. Zhan M. Hsu V.D. et al.The frequency of hyperkalemia and its significance in chronic kidney disease.Arch Intern Med. 2009; 169: 1156-1162https://doi.org/10.1001/archinternmed.2009.132Crossref PubMed Scopus (397) Google Scholar Nevertheless, the increased rates of hospitalization and mortality associated with predialysis sK+ concentration >5.5 mmol/l2Karaboyas A. Zee J. Brunelli S.M. et al.Dialysate potassium, serum potassium, mortality, and arrhythmia events in hemodialysis: results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).Am J Kidney Dis. 2017; 69: 266-277https://doi.org/10.1053/j.ajkd.2016.09.015Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar challenge the use of a target of 6.0 mmol/l. In our analysis, nearly two-thirds of hemodialysis patients with severe hyperkalemia receiving SZC achieved a target predialysis sK+ concentration range of 4.0 to 5.5 mmol/l for ≥3 of 4 hemodialysis treatments after the LIDI and will be expected to be at lower risk of adverse events associated with higher predialysis sK+ concentrations. These analyses have limitations. The analyses are post hoc and were not prespecified; therefore, the results are exploratory. Patient numbers within each predialysis sK+ subgroup were small and not powered to investigate treatment associations, which limits the interpretation of our findings. Finally, we did not evaluate the impact of severe hyperkalemia on safety outcomes, such as cardiovascular events. Regarding this point, the DIALIZE-Outcomes study (EudraCT 2020-005561-14) will evaluate the effect of SZC on arrhythmia-related cardiovascular outcomes among chronic hemodialysis patients with recurrent hyperkalemia (predialysis sK+ concentration ≥5.5 mmol/l). In conclusion, these post hoc findings suggest that SZC could be an effective addition to maintenance hemodialysis in reducing predialysis sK+ concentration in patients with end-stage kidney disease and severe hyperkalemia who are at high risk of adverse events. The extended target predialysis sK+ range of 4.0 to 5.5 mmol/l seemed to negate the impact of severe hyperkalemia. Evidence of the effectiveness of SZC in this subgroup of DIALIZE has clinical relevance and potential applicability beyond the tight confines of a clinical trial setting. MF reports receiving travel support from Amgen and AstraZeneca and serving as an advisory board member for AstraZeneca. SF reports receiving research support and consulting fees from AstraZeneca. BS reports receiving research grants, lecture fees, and/or consulting fees from AstraZeneca, Akebia, Reata Pharmaceuticals, and Fresenius Medical Care. AR reports receiving research or travel support from and/or is a speaker, consultant, or advisory board member for AstraZeneca, Vifor Pharma, Fresenius Medical Care, Sanofi, Kadmon, AMAG, Otsuka, Genzyme, GlaxoSmithKline, Omeros, Janssen, Reata Pharmaceuticals, Ironwood, and Amgen. NG reports being an employee of AstraZeneca. KM reports being an academic grant holder and an advisory board member for AstraZeneca. The primary DIALIZE study and this post hoc analysis were supported by AstraZeneca . The authors thank the patients, their families, and all investigators involved in the DIALIZE study, the dialysis services and research staff in each participating center, and the following members of the data monitoring committee: David Charytan, MD, Charles Herzog, MD, and David Wheeler, MD. Medical writing support was provided by Shaun W. Foley, BSc (Hons) CMPP, and editorial support was provided by Sinead Stewart, both of Core, London, UK, supported by AstraZeneca according to Good Publication Practice guidelines (https://www.acpjournals.org/doi/10.7326/M15-0288). The sponsor was involved in the study design; collection, analysis, and interpretation of data; and data checking of information provided in the manuscript. Ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors. Data underlying the findings described in this manuscript may be obtained in accordance with AstraZeneca’s data-sharing policy described at https://astrazenecagroup-dt.pharmacm.com/DT/Home. All authors contributed to the data interpretation, critically reviewed the manuscript, approved the final version, and accept accountability for the overall work. Download .pdf (.33 MB) Help with pdf files Supplementary File (PDF) Supplementary Methods. Supplementary Results. Supplementary References. Table S1. Baseline patient characteristics by baseline predialysis sK+ subgroup (<6.0 mmol/l and ≥6.0 mmol/l). Table S2. Doses of SZC and placebo at the end of the dose titration period, by baseline predialysis sK+ subgroup (<6.0 mmol/l and ≥6.0 mmol/l). Table S3. Events of pre- and post-dialysis hypokalemia (sK+ <3.5 mmol/l), by baseline predialysis sK+ subgroup (<6.0 mmol/l and ≥6.0 mmol/l). Figure S1. Mean predialysis sK+ concentrations at LIDI visits during the 4-week evaluation period by treatment arm and baseline predialysis sK+ subgroup (≥6.0 mmol/l and <6.0 mmol/l). STROBE Statement (PDF)

131P - Cabozantinib in Asian patients with hepatocellular carcinoma and other solid tumours: Population pharmacokinetics analysis

BackgroundCabozantinib, an inhibitor of MET, AXL and VEGF receptors, was recently approved for the treatment of patients with advanced hepatocellular carcinoma (HCC) who had previously received sorafenib, based on findings of the CELESTIAL trial. We previously reported cabozantinib pharmacokinetics (PK) data based on 9 cabozantinib studies (N = 1534), Here, we report updated cabozantinib PK data in Asian and non-Asian ethnicities including patients with HCC. MethodsWe used data from ten cabozantinib studies that included healthy volunteers (HV) and patients with various cancer types (HCC, renal cell carcinoma, castration-resistant prostate cancer, medullary thyroid cancer [MTC], and glioblastoma multiforme). Studies pertinent to HCC were the CELESTIAL trial (NCT01908426) and the HCC cohort of a phase 2 trial (NCT00940225). The impact on PK parameters of selected covariates (age, weight, sex, race, cancer type, formulation, and liver dysfunction according to the National Cancer Institute Organ Dysfunction Working Group [NCI-ODWG]) was evaluated. Steady-state PK parameters were predicted for Asian and non-Asian patients. ResultsData from 2023 individuals were included (cancer patients, n = 1883; HV, n = 140), of whom 211 were of Asian ethnicity and 1812 of non-Asian ethnicity. MTC cancer type had the largest effect on cabozantinib PK parameters, with a 90% increase in apparent clearance (CL/F) relative to HV. Other cancer types, including HCC, and liver dysfunction per NCI-ODWG did not impact cabozantinib PK. However, because CELESTIAL excluded patients with Child-Pugh scores of B or C, results on patients with more compromised liver function are limited. A 24% decrease in CL/F was observed in females; Asian ethnicity, age, and weight had no clinically significant impact on cabozantinib clearance. ConclusionsMinimal cabozantinib PK and predicted exposure differences were observed across various cancer types except for MTC. The PK of cabozantinib was similar in individuals of Asian and non-Asian ethnicity. These findings are consistent with the major metabolic pathway of cabozantinib via cytochrome P450 3A4 which is not prone to genetic polymorphism. Editorial acknowledgementThe authors thank Isabelle Kaufmann, PhD of Oxford PharmaGenesis, Oxford, UK for providing medical writing support, which was sponsored by Ipsen, Abingdon, UK in accordance with Good Publication Practice guidelines. Legal entity responsible for the studyIpsen. FundingIpsen. DisclosureC-H. Hsu: Research grant/Funding (self): Ipsen; Honoraria (self): Ipsen. L. Nguyen: Full / Part-time employment: Exelixis. A-L. Cheng: Honoraria (self): Bayer; Honoraria (self): Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self): Merck Serono; Honoraria (self): Novartis; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Roche/Genentech; Honoraria (self): IQVIA. Advisory/Consultancy: Bayer Schering Pharma; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Eisai; Advisory/Consultancy: Merck Serono; Advisory/Consultancy: Novartis; Advisory/Consultancy: Ono Pharmaceutical; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Nucleix Ltd.; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: IQVIA. Speaker Bureau/Expert testimony: Bayer Yakuhin, Ltd.; Speaker Bureau/Expert testimony: Novartis; Speaker Bureau/Expert testimony: Eisai; Speaker Bureau/Expert testimony: Ono Pharmaceutical; Speaker Bureau/Expert testimony: Amgen Taiwan. Travel/Accommodation/Expenses: Bayer Yakuhin, Ltd.; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Eisai; Travel/Accommodation/Expenses: Ono Pharmaceutical; Travel/Accommodation/Expenses: Roche/Genentech; Travel/Accommodation/Expenses: IQVIA. T.X.Q. Nguyen: Full / Part-time employment: Ipsen. K. Brendel: Full / Part-time employment: Ipsen. V. Aslanis: Full / Part-time employment: Ipsen. F. Benzaghou: Full / Part-time employment: Ipsen.

201P - Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial

BackgroundAsymptomatic nmCRPC patients (pts) would benefit from treatments (Tx) that delay disease progression and maintain quality of life (QoL), with minimal Tx-related adverse events (AEs). In ARAMIS, darolutamide (DARO) prolonged metastasis-free survival vs placebo (PBO) (40 vs 18 months; HR 0.41; 95% CI 0.34–0.50; P < 0.001); impact on prostate-specific antigen (PSA), disease progression, safety, and QoL in ARAMIS is reported here. MethodsPts were randomized to DARO 600 mg twice daily (n = 955) or PBO (n = 554), while androgen deprivation therapy continued in both arms. Secondary/exploratory endpoints included safety, time to cytotoxic chemotherapy, time to antineoplastic therapy, time to PSA progression, and QoL. ResultsDARO substantially delayed times to PSA progression (33 vs 7 months; HR 0.13; 95% CI 0.11–0.16; P < 0.001), cytotoxic chemotherapy (not reached [NR] vs 38 months; HR 0.43; 95% CI 0.31–0.60; P < 0.001), and antineoplastic therapy (NR vs NR; HR 0.33; 95% CI 0.23–0.47; P < 0.001) vs PBO. The distribution of sites of distant metastases was similar between groups: 60/130 (46%) and 62/158 (39%) had bone-only metastases, 41/130 (32%) and 63/158 (40%) had lymph node-only metastases, while 17/130 (13%) and 22/158 (14%) had both lymph node and bone metastases, in the DARO and PBO groups, respectively. Distant metastases at other sites were also similar, occurring in 12/130 (9%) and 11/158 (7%) of pts in the DARO and PBO groups, respectively. Incidences of Tx-emergent AEs with ≥5% frequency or of grade 3–5 were comparable between DARO and PBO; none except fatigue occurred in > 10% of pts. Discontinuation rates due to AEs were 8.9% with DARO and 8.7% with PBO. AEs noted with other androgen receptor inhibitors (including fracture, falls, seizures, hypertension and cognitive disorder) showed minimal or no difference in incidence between groups. DARO maintained QoL, and delayed the onset of pain and disease-related urinary symptoms compared with PBO. ConclusionsDARO delays disease progression and subsequent Tx for metastatic castration-resistant prostate cancer vs PBO, maintaining QoL without increasing incidence of key AEs. Clinical trial identificationNCT02200614. Editorial acknowledgementMedical writing support for the development of this abstract was provided by Lucy Smithers, PhD, and editorial support, including formatting, proofreading, and submission was provided by Beth King, both of Scion Medica, London, supported by Bayer according to Good Publication Practice guidelines. Legal entity responsible for the studyOrion Corporation, Orion Pharma and Bayer AG. FundingOrion Corporation and Bayer AG. DisclosureJ.S-T. Pang: Non-remunerated activity/ies, Writing support: Bayer. N. Shore: Advisory / Consultancy, Research grant / Funding (self): Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Advisory / Consultancy, Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Dendreon; Advisory / Consultancy, Research grant / Funding (self): Tolmar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self): Myovant Sciences; Advisory / Consultancy, Research grant / Funding (self): Merck; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy, Research grant / Funding (self): Nymox. M.R. Smith: Honoraria (self): Amgen; Honoraria (self): Astellas; Honoraria (self): Bayer; Honoraria (self): Clovis; Honoraria (self): Gilead; Honoraria (self): Janssen; Honoraria (self): Lilly; Honoraria (self): Novartis; Honoraria (self): Pfizer. T.L. Tammela: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (self): Lidds AB; Advisory / Consultancy, Research grant / Funding (self): Astellas. E. Vjaters: Research grant / Funding (self): Ipsen; Research grant / Funding (self): Bayer; Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Orion. M. Jievaltas: Honoraria (self): Bayer; Honoraria (self): Ipsen; Honoraria (self): Janssen. M. Luz: Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Research grant / Funding (self): Janssen; Research grant / Funding (self): AstraZeneca; Travel / Accommodation / Expenses: Pfizer; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Research grant / Funding (self): Ferring; Speaker Bureau / Expert testimony: Sanofi. B. Alekseev: Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Bayer; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Astellas; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: BMS; Honoraria (self), Non-remunerated activity/ies: Ferring; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Janssen; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: MSD; Honoraria (self), Research grant / Funding (self), Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), Non-remunerated activity/ies: Sanofi. I. Kuss: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bayer. M-A. Le Berre: Full / Part-time employment: Bayer Healthcare. A. Snapir: Full / Part-time employment: Orion Pharma. T. Sarapohja: Full / Part-time employment: Orion Corporation. K. Fizazi: Honoraria (self), Advisory / Consultancy: Astellas Pharma; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self): Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Curevac; Advisory / Consultancy: ESSA; Advisory / Consultancy: Orion Pharma; Advisory / Consultancy: Roche/Genentech. All other authors have declared no conflicts of interest.

754P - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study

BackgroundCELESTIAL (NCT01908426), a phase 3 study in patients with aHCC who progressed on sorafenib (≤2 previous systemic treatments allowed), demonstrated improved survival and progression-free survival with cabozantinib over placebo. CELESTIAL was stopped early for benefit at the second interim analysis (hazard ratio for death in overall population, 0.76 [95% confidence interval 0.63–0.92; p=0.005] resulting in short follow-up for some patients). This retrospective analysis compared patient experience of three discrete health states in patients receiving second-line cabozantinib vs placebo in CELESTIAL: time with grade 3/4 toxicity before progression (TOX); time without grade 3/4 toxicity before progression (TWiST); and survival time after progression or relapse (REL). MethodsOverall, 495 patients in CELESTIAL had sorafenib as the only prior therapy (cabozantinib, 331; placebo, 164). For each patient, times spent in TOX, TWiST and REL were calculated. Toxicities were based on reported adverse events. Patients censored prior to progression or death (32%) accrued time in each health state up to that date. ResultsSecond-line cabozantinib was associated with significantly longer mean TOX (49.8 vs 9.8 days, p<0.0001), and also TWiST (110.9 vs 78.1 days, p=0.001) than placebo; survival times after progression (REL) were similar; (Table). Analyses based on all patients in CELESTIAL (N=707) or limited to those with ≥100 days of follow-up (regardless of whether they had a progression event prior to that time) resulted in numerically different estimates for each health state, but no qualitative differences in findings. ConclusionsPatients with aHCC receiving second-line cabozantinib after sorafenib spent significantly more time without disease symptoms and toxicity than those receiving placebo, despite an increase in days with grade 3/4 toxicity before progression.Table754PTableHealth stateCabozantinib (N=331) Mean days (95% CI)Placebo (N=164) Mean days (95% CI)Difference cabozantinib - placebo Mean days (95% CI; t test)TOX49.8 (39.2–60.3)9.8 (2.6–17.0)40.0 (27.3–52.7; p<0.0001)TWiST110.9 (96.7–125.2)78.1 (64.7–91.5)32.8 (13.3–52.3; p=0.001)REL174.5 (152.5–196.5)178.6 (144.1–213.0)-4.1 (-43.5–35.4; p=0.85)CI, confidence interval; REL, survival time after progression/relapse; TOX, time with a grade 3/4 toxicity before progression; TWiST, time without disease symptoms and grade 3/4 toxicity Clinical trial identificationNCT01908426. Editorial acknowledgementOxford PharmaGenesis, Oxford, UK for providing editorial support, which was sponsored by Ipsen, Abingdon, UK in accordance with Good Publication Practice guidelines. Legal entity responsible for the studyIpsen. FundingIpsen. DisclosureN. Freemantle: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Biogen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Yesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Allergan; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PTC; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca. G.K. Abou-Alfa: Advisory / Consultancy: 3DMedcare; Advisory / Consultancy, Research grant / Funding (institution): Agions; Advisory / Consultancy: Alignmed; Advisory / Consultancy: Antengene; Advisory / Consultancy: Aptus; Advisory / Consultancy: Aslan; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Beigene; Advisory / Consultancy: Bioline; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Boston Scientific; Advisory / Consultancy: Bridgebio; Advisory / Consultancy: Carsgen; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy, Research grant / Funding (institution): Casi; Advisory / Consultancy: Cipla; Advisory / Consultancy: Cytom X; Advisory / Consultancy: Daiichi. A. Cheng: Honoraria (self): Bayer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self): Merck Sharp Dohme; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: IQVIA; Advisory / Consultancy: Bayer Schering Pharma; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Nucleix Ltd.; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer Yakuhin, Ltd; Speaker Bureau / Expert testimony: Amgen Taiwan. R.K. Kelley: Advisory / Consultancy: Genentech/ Roche; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Agios; Advisory / Consultancy, Research grant / Funding (institution): BMS; Research grant / Funding (institution): Adaptimmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): QED; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Medimmune; Research grant / Funding (institution): Taiho. V. Valcheva: Full / Part-time employment: Ipsen. F. Benzaghou: Full / Part-time employment: Ipsen. P. Mollon: Full / Part-time employment: Ipsen.

890P - Assessing the clinical relevance of drug-drug interactions (DDI) with darolutamide (DARO)

BackgroundDARO is an androgen receptor antagonist with a distinct molecular structure, which has demonstrated prolonged metastasis-free survival vs placebo (PBO) in the phase 3 ARAMIS study in non-metastatic castration-resistant prostate cancer patients. These typically older patients often receive multiple comedications. We assessed DDIs with DARO both in vitro and in clinical trial development. MethodsThe effects of induction and inhibition of transporters and CYP enzymes on DARO, and the effect of DARO on other comedications were studied in vitro and in several phase 1 trials using rifampicin (CYP3A4, P-gp inducer), itraconazole (ICZ; CYP3A4, P-gp inhibitor), rosuvastatin (BCRP, OATP1B1, OATP1B3 and OAT3 substrate), midazolam (CYP3A4 substrate) and dabigatran etexilate (P-gp substrate). The impact of comedication on DARO was investigated in a population pharmacokinetic (popPK) and covariate analysis of a subset of ARAMIS patients. The adverse event (AE) profile for comedication use between PBO and DARO was also analysed. ResultsConcomitant rifampicin led to a 3.5-fold decrease in DARO area under the curve (AUC) vs DARO alone. ICZ resulted in 1.8-fold increase in DARO AUC vs DARO alone. No significant effect of comedications that are CYP or P-gp inhibitors was identified in the popPK analysis; proton pump inhibitors did not significantly affect the PK of DARO. Effects of DARO on CYP inhibition in vitro were negligible and coadministration of midazolam or dabigatran showed no clinically relevant effects. Rosuvastatin AUC increased by 5.2-fold with DARO vs rosuvastatin alone, attributed mainly to BCRP inhibition. The incidence of AEs in ARAMIS was low; comedication use (98.7% in DARO, 98.0% in PBO arms) and AE profile were similar between study arms. ConclusionsDDIs with DARO and P-gp or CYP enzyme substrates, e.g. antithrombotics, calcium channel blockers or proton pump inhibitors, are not expected. Strong CYP3A4 inducers, e.g. rifampicin and carbamazepine, showed some interaction with DARO. Effects of CYP3A4 or P-gp inhibitors on DARO were not considered clinically relevant. DARO may increase the exposure of concomitant BCRP substrates, e.g. statins, although a safety and AE analysis from ARAMIS did not indicate any relevant impact of DARO. Clinical trial identificationNCT03237416, NCT03048110, NCT02671097, NCT02200614. Editorial acknowledgementMedical writing support: Lucy Smithers, PhD, and editorial support: Beth King, both of Scion Medica, London, supported by Bayer according to Good Publication Practice guidelines. Legal entity responsible for the studyBayer. FundingBayer and Orion Corporation. DisclosureC.R. Zurth: Full / Part-time employment: Bayer. K. Fizazi: Honoraria (self), Advisory / Consultancy: Merck, Sharp & Dohme; Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas; Advisory / Consultancy: Orion; Advisory / Consultancy: CureVac; Advisory / Consultancy: Clovis. R. Fricke: Full / Part-time employment: Bayer. H. Gieschen: Full / Part-time employment: Bayer. K. Graudenz: Full / Part-time employment: Bayer. M. Koskinen: Full / Part-time employment: Orion Corporation. B.A. Ploeger: Full / Part-time employment: Bayer. O. Prien: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bayer. M.R. Smith: Advisory / Consultancy: Bayer; Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy: Clovis; Advisory / Consultancy: Gilead; Honoraria (self): Hinova; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Pfizer. T. Tammela: Honoraria (self), Research grant / Funding (institution): Bayer; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution): Lidds AB; Advisory / Consultancy, Research grant / Funding (institution): Astellas. N.D. Shore: Advisory / Consultancy, Research grant / Funding (self): Ferring; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Research grant / Funding (self): Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Dendreon; Advisory / Consultancy, Research grant / Funding (self): Tolmar; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas.

Good Practice for Conference Abstracts and Presentations: GPCAP

Research that has been sponsored by pharmaceutical, medical device and biotechnology companies is often presented at scientific and medical conferences. However, practices vary between organizations and it can be difficult to follow both individual conference requirements and good publication practice guidelines. Until now, no specific guidelines or recommendations have been available to describe best practice for conference presentations.This document was developed by a working group of publication professionals and uploaded to PeerJ Preprints for consultation prior to publication; an additional 67 medical societies, medical conference sites and conference companies were also asked to comment. The resulting recommendations aim to complement current good publication practice and authorship guidelines, outline the general principles of best practice for conference presentations and provide recommendations around authorship, contributorship, financial transparency, prior publication and copyright, to conference organizers, authors and industry professionals.While the authors of this document recognize that individual conference guidelines should be respected, they urge organizers to consider authorship criteria and data transparency when designing submission sites and setting parameters around word/character count and content for abstracts. It is also important to recognize that conference presentations have different limitations to full journal publications, for example, in the case of limited audiences that necessitate refocused abstracts, or where lead authors do not speak the local language, and these have been acknowledged accordingly. The authors also recognize the need for further clarity regarding copyright of previously published abstracts and have made recommendations to assist with best practice.By following Good Practice for Conference s and Presentations: GPCAP recommendations, industry professionals, authors and conference organizers will improve consistency, transparency and integrity of publications submitted to conferences worldwide.

75P - Cemiplimab, a human PD-1 monoclonal antibody, in patients (pts) with recurrent or metastatic cervical cancer: Interim data from phase I cohorts

Background: For pts who progress after first-line platinum based therapy for recurrent/metastatic cervical cancer, there are no therapies available that have been demonstrated to improve survival or quality of life. Cemiplimab (REGN2810), a human monoclonal antibody to PD-1, exhibited encouraging efficacy and acceptable tolerability in a phase 1 dose escalation study. The present report focuses on interim data from the phase 1 cervical cancer expansion cohorts (ECs) of cemiplimab as a monotherapy (EC 23) or in combination with hypofractionated radiotherapy (hfRT) (EC 24) (NCT02383212). Methods: Pts with recurrent or metastatic cervical cancer resistant to or intolerant of platinum and taxane doublet therapy received cemiplimab 3 mg/kg Q2W IV for up to 48 weeks, in ECs 23 and 24, and hfRT (9 Gy x 3 times/week given 1 week after first dose of cemiplimab) in EC 24. The co-primary objectives were to evaluate the safety, tolerability, and efficacy of cemiplimab monotherapy or in combination with hfRT. Tumour response assessments (in non-irradiated target lesions) were performed by RECIST 1.1 Q8W. Results: As of 1 Sept, 2017, these ECs were fully enrolled with 20 pts (EC 23, n = 10, EC 24, n = 10). Median (range) age was 55.0 (31–76) years (EC 23) and 51.5 (29–65) years (EC 24). ECOG performance status 1 vs. 0 was 60% vs. 40% and 80% vs. 20%, respectively, for EC 23 and EC 24. Investigator-assessed overall response rate (ORR; complete response [CR] + partial response [PR]) was 10.0% (0 CR and 1 PR) in each of EC 23 and EC 24. At the time of data cut-off, both responses were ongoing with durations of 3.7+ months. The most common treatment-emergent adverse events (TEAEs) of any grade were diarrhoea (40.0%), fatigue, hypokalaemia and pain in extremity (each 30.0%) in EC 23, and diarrhoea and urinary tract infection (each 30.0%) in EC 24. There was no grade ≥3 TEAE reported in > 1 patient in either cohort. Conclusions: Cemiplimab as monotherapy and in combination with hfRT demonstrated antitumour activity with an acceptable safety profile in pts with metastatic or recurrent cervical cancer. Cemiplimab monotherapy vs. chemotherapy in ≥ 2nd line cervical cancer is currently being evaluated in a global randomised phase 3 study (NCT03257267). Editorial acknowledgement: Medical writing support under the direction of the authors was provided by Emmanuel Ogunnowo, PhD, of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines. Clinical trial identification: NCT02383212. Legal entity responsible for the study: Regeneron Pharmaceutical Inc. and Sanofi. Funding: Regeneron Pharmaceutical Inc. and Sanofi. Disclosure: D. Rischin: Research funding: Genentech/Roche, Merck, Amgen, Regeneron, Bristol-Myers Squibb. A. González-Martin: Consulting, advisory, speakers’ bureau, travel accommodation expenses: AstraZeneca, Tesaro, Roche, Pharmamar. J.Y. Hou: Consultant and fees: Foundation Medicine, Massive Bio, Inc. D. Cho: Consulting fees: Pfizer, BMS, Exelixis, Genentech, Prometheus. G. Falchook: Funding for trial for submitted work. S. Jabbour: Research funding grants: Merck, Nestle outside of the submitted work. K. Moore: KInstitutional consultancy (honorarium and ad board) fees: Tesaro, Genentech Roche, Clovis, AstraZeneca (for agents not involved in the SOLO-1 study), Immunogen, VBL Therapeutics, Janssen. M.G. Fury: Employee and shareholder: Regeneron Pharmaceuticals, Inc.; Patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. M. Feng: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Bayer. J. Li: Employee and shareholder: Regeneron Pharmaceuticals, Inc., Novartis. I. Lowy: Employee, shareholder, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M. Mathias: Employee and shareholder: Regeneron Pharmaceuticals, Inc. All other authors have declared no conflicts of interest.

71P - Phase I study of cemiplimab, a human monoclonal anti-PD-1, in patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC): Longer follow-up efficacy and safety data

Background: Cemiplimab (REGN2810) demonstrated a positive risk/benefit profile and produced antitumour activity in patients (pts) with advanced CSCC in the primary analysis, by independent central review, of a phase 1 CSCC expansion cohorts (ECs). We now report longer follow-up data from the CSCC ECs of the phase 1 study (NCT02383212). Methods: Pts with distantly metastatic or locally/regionally advanced CSCC who were not candidates for surgery were enrolled in ECs 7 and 8, respectively. All pts received cemiplimab 3 mg/kg by intravenous infusion over 30 minutes every 2 weeks for up to 48 weeks. Tumour measurements were performed every 8 weeks by RECIST 1.1 to determine overall response rate (ORR; complete response [CR] + partial response [PR]) according to intention to treat. The data cut-off date was Jan 20, 2018. Tumour response in this report was by investigator assessment. Results: A total of 26 pts were enrolled (21 M/5 F; 10 in EC 7, 16 in EC 8; median age: 72.5 years [range: 55–88]; ECOG performance status was 1 in 16 pts and 0 in 10 pts). Median duration of follow-up was 11.9 months (range: 1.1–18.2). Median duration of cemiplimab exposure was 36.0 weeks. The most common treatment-emergent adverse event (TEAE) of any grade was fatigue (26.9%). The only TEAEs of grade ≥3 that occurred in more than one pt were hypercalcaemia and skin infection (each 7.7%). ORR was 50.0% (95% CI: 29.9–70.1), with 2 CRs and 11 PRs; 5 patients had stable disease (SD), 6 had progressive disease, and 2 were not evaluable for response. Durable disease control rate (SD or response for ≥105 days) was 57.7% (95% CI: 36.9–76.6). The median time to response was 1.9 months (range: 1.7–7.5). The median duration of response has not been reached, and as of the data cut-off date, for pts with CR or PR, the observed duration of response exceeded 6 months in 9 pts and 12 months in 5 pts. Conclusions: The increasing duration of response in this analysis provides further evidence of a positive risk/benefit profile for cemiplimab in pts with advanced CSCC. Editorial acknowledgement: Medical writing support under the direction of the authors was provided by Emmanuel Ogunnowo, PhD, of Prime (Knutsford, UK) and funded by Regeneron Pharmaceuticals, Inc. and Sanofi according to Good Publication Practice guidelines. Clinical trial identification: NCT02383212. Legal entity responsible for the study: Regeneron Pharmaceutical, Inc. and Sanofi. Funding: Regeneron Pharmaceutical, Inc. and Sanofi. Disclosure: T.K. Owonikoko: Fees for consulting or advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, MedImmune. A.K. Salama: Fees for consulting or advisory and speakers’ bureau roles: Bristol-Myers. E. Calvo: Research funding: Boehringer Ingelheim, Roche/Genentech, BMS, Novartis, PsiOxus, Nanobiotix, Janssen, Abbvie, PharmaMar, PUMA, Sanofi, Lilly, Pfizer, Merck, Nektar, Amcure, Amgen, AstraZeneca, Principia, Bayer, CytomX, H3, Incyte, Kura, Loxo, Macrogenics, Menarini, Merck, Serono, Merus, Millenium, Rigontec, Tahio, TesaroReceipt; Honoraria or consultation fees: Novartis, Nanobiotix, Janssen-Cilag, PsiOxus Therapeutics, Seattle Genetics, Pierre Fabre, Boehringer Ingelheim, Cerulean Pharma, EUSA, Abbvie, Celgene; Speaker’s bureau fees: Novartis. N.S. Yee: Institutional research funding: Boston Biomedical Inc., Merck and Co. Inc., Pharmacyclics, Regeneron Pharmaceuticals Inc; Travel/accommodation expenses: Daiichi Sankyo, Foundation Medicine, Caris Life Sciences. D. Mahadevan: Speakers’ bureau and travel, accommodation expenses: Abbvie. J. Niu: Consulting or advisory role fees: Genentech, Biodesix, Paradigm, Ignyta, AstraZeneca and Teueda. K. Kal Mohan: Employee and shareholder of Regeneron Pharmaceuticals, Inc. J. Li: Employee and shareholder of Regeneron Pharmaceuticals, Inc. and Novartis. E. Stankevich: Employee of Regeneron Pharmaceuticals, Inc., a shareholder of Regeneron Pharmaceuticals, Inc., Celgene, Bristol-Myers Squibb, and Merck. M. Mathias: Shareholder and an employee of Regeneron Pharmaceuticals, Inc. I. Lowy: Employee, shareholder, fees for travel and accommodation expenses, leadership: Regeneron Pharmaceuticals, Inc. M.G. Fury: Employee and shareholder of Regeneron Pharmaceuticals, INC.; patents, royalties, other intellectual property: Regeneron Pharmaceuticals, Inc. H.M. Babiker: Honoraria: Bayer, Sirtex; Consulting or advisory role fees: Celgene, Endocyte. All other authors have declared no conflicts of interest.

Response to Vallance

Sir, In response to Dr Vallance's letter,1 we refute the implication that this article2 is an example of ‘medical ghostwriting'. Alpha-Plus Medical Communications acts in accordance with good publication practice guidelines (GPP2) as published in the BMJ,3 and confirms that there was no exception with this article. The authors provided direction, had full control of the editorial content, and accepted full responsibility for views and opinions as well as accuracy of the content.4 A clear and unambiguous statement regarding our involvement in this publication was included in the acknowledgements. In relation to Dr Vallance's claim that Alpha-Plus provides ‘complete medical communication services for all marketing needs', we would like to highlight that the source of this statement is an out-of-date and obsolete business listing from early 2009. We thank Dr Vallance for drawing our attention to this listing and have requested that it is removed at the earliest opportunity. Please refer your reader to our website (http://www.fishawack.com) for up-to-date and accurate information regarding our group of companies. As you will note on our website, publication activities are separate from other medical communications services. We would like to add that with regard to comments made about the appointment of Jo Jarvis, the conference in which Jo participated focused on how the industry should interact with different stakeholder groups (including physicians) in an ethically responsible manner and in compliance with the latest code of practice governing this area.

Authorship Policy of the Journal of Korean Medical Science

The Journal of Korean Medical Science (JKMS) follows the recommendations for authorship by the International Committee of Medical Journal Editors (ICMJE, 2008, www.icmje.org) and the Good Publication Practice Guidelines by the Korean Association of Medical Journal Editors (KAMJE, 2008, www.kamje.or.kr). The Uniform Requirements by the ICMJE recommends authorship as follows. credit should be based on 1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; 2) drafting the article or revising it critically for important intellectual content; and 3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3. Beyond the ICMJE recommendations, the KAMJE guidelines suggest that all authors should make a substantial intellectual contribution to the publication, the guidelines warn against authorship abuse, and list common types of abuse. Authorship is an important aspect of research publication, and all involved authors should agree whole contents of the document including authorship. Contributors should be differentiated from authors as recommended by the ICMJE. JKMS does not allow multiple corresponding authors for one article even when it is reporting on a multicenter study. Only one author should correspond with the editorial office and readers for one article. JKMS accepts notice of equal contribution for the first author when the study was clearly performed by co-first authors. However, the present issue of JKMS (Vol. 25 No. 5: 734-7) publishes one article which has two corresponding authors. The article, which is titled Optimal Waist Circumference Cutoff Values for Metabolic Syndrome Diagnostic Criteria in a Korean Rural Population, is published exceptionally because the authorship policy of JKMS has not been open declared yet. The authorship policy is declared open through this editorial and also at the homepage of JKMS, http://jkms.org. JKMS does not correct authorship after publication unless any mistake has been made by the editorial or publishing staff. Authorship may be changed before publication but after submission when an authorship correction is requested by all authors involved.

What Medical Writing Means To Me

This is a personal account based on many years experience as a medical writer. It considers aspects of medical writing with particular focus on the intellectual and ethical dilemmas it can raise. What makes medical writing both so interesting and so challenging is the fact that it often takes place at the border between different disciplines. For example, it straddles both science and art. Ethical issues also arise at the boundaries between academia and commerce. Until recently there have been few guidelines to help navigate such potentially dangerous territory. I have been privileged to be involved in developing two such guidelines and I describe how I hope the Good Publication Practice guidelines for pharmaceutical companies and the European Medical Writers Association guidelines may improve the practice of this fascinating profession, Medical Writing.

A concern that drug companies cannot ignore

A report by the House of Commons Health Committee into the influence of the UK pharmaceutical industry has recommended that companies should publish the results of all their trials and follow guidelines for responsible publication practice.1 Cynics may argue that such reports rarely have much influence over powerful commercial companies and that governments usually ignore their recommendations unless they support existing policies. But this call for greater transparency and responsibility echoes similar calls which, taken together, form a crescendo that is hard to ignore. Earlier events that may have focused the minds of drug companies and made them more receptive to the latest recommendations include the fine of $240 million plus $152 million damages awarded against Pfizer/Warner-Lambert in May 2004 for promoting off-label use of its anticonvulsant gabapentin.2 Promotional activities criticized by the US court included having a publication strategy that encouraged the production and dissemination of anecdotal reports of dubious scientific value and the use of ghost-writers to prepare favourable articles which appeared under the names of opinion leaders. Less than a month later, the New York Attorney General accused GlaxoSmithKline of failing to publish safety data about its antidepressant paroxetine. This case was settled out of court but the company agreed to post results from all its clinical trials on its website.3 Several other companies have followed suit,4 and the Pharmaceutical Research Manufacturers of America (the US industry association) has set up a website for this purpose.5 Later in 2004, the International Committee of Medical Journal Editors announced that, from mid-2005, journals edited by the 12 committee members would consider papers for publication only if the trial had been registered.6 Other journals have now adopted similar policies.7 In the USA, registration of trials in serious and life-threatening conditions has been required by the Food and Drug Administration for a few years, but the system has not been policed particularly thoroughly and it is not clear what happens if companies do not comply or provide incomplete information. In contrast, the journal editors' announcement not only included a sanction that companies would respect (i.e. the threat of not being able to publish in several prestigious journals) but has also been followed by clarification about the type of information required and warnings that journals will check companies' compliance.8 Support for trial registration and complete publication is also found in the latest revision of the Declaration of Helsinki which calls for the design of studies to be made available prospectively and for both negative and positive results to be published.9 Picking up these themes, the House of Commons report presents cogent arguments why publication bias, and, in particular, the suppression of negative findings, is harmful and supports demands for trial registration. The question of ghost-writing has also received attention in both medical journals and newspapers for some time.10,11 Once again, the House of Commons Committee has added its voice to the debate by calling on companies to behave responsibly. The report refers to the guidelines issued recently by the European Medical Writers Association which seek to abolish ghost-writing by encouraging proper acknowledgement of medical writers' contributions to articles and their source of funding.12 One problem with the discussion over ghost-writing has been confusion over exactly what is meant by the term. In this respect, the House of Commons report is helpful in recognizing that it is acceptable for professional medical writers to help doctors write up their research but in condemning the practice of preparing articles with insufficient input from named authors and of covering-up the role of writers or funding companies. This distinction between the legitimate role of professional writers and authorship abuses by pharmaceutical companies has also been emphasized in a recent position statement from the World Association of Medical Editors (WAME).13,14 The statement recommends that journals should make clear in their information for authors that medical writers can be legitimate contributors but that their roles and affiliations should be acknowledged. The issues raised by the involvement of professional writers are also covered in the Good Publication Practice (GPP) guidelines which are strongly endorsed by the parliamentary Committee's report.15 These guidelines were developed in response to concerns that drug companies were skewing the medical literature by failing to publish unfavourable findings and by publishing positive results repeatedly. The GPP guidelines therefore call on companies to endeavour to publish results of all trials of marketed products. This suggestion is taken up by the report which calls on companies to make results of all trials available 'at launch as a condition of the marketing licence'. If the UK regulatory authorities act on this it might ensure the implementation of such codes which have, until now, been voluntary. However, European drug regulation is highly centralized, and it is unlikely that the UK would take unilateral action especially over a measure that might be resented by the industry. The Committee also suggests that research ethics committees should 'require applicants to prove' that a proposed trial 'does not duplicate previous research' and to ensure 'that results will be published in full'. However, similar ideas were proposed over a decade ago,16 and have been aired more recently,17 suggesting that ethics committees are unable or unwilling to take on this extra burden. While many of the recommendations relating to trial registration and publication simply echo or amplify statements from other groups, the Committee took a more radical approach to the drug licensing process. It was particularly critical of the Medicines and Healthcare products Regulatory Agency (MHRA—the UK drug licensing authority), calling for a 'fundamental review' in view of its (unspecified) 'failings'. The report urges the MHRA to publish material submitted by companies to support licensing applications. This would be an important change from the current situation where such information is considered confidential. However, the secrecy of drug licensing and the lack of information available to prescribers about new products has been criticized for many years by other commentators,18 so it will be interesting to see whether this House of Commons Committee wields more influence. Some of the reforms proposed by the Committee could constrain prescribing freedom, since it favours a system of limiting the prescribing of new products to hospital specialists and calls for increased monitoring of nurse and pharmacist prescribing. The report concludes that 'it is extraordinary that there are stricter controls on hospital specialists prescribing than on GPs' and recommends that 'tougher restrictions' should be placed 'on what non-specialists can prescribe' with 'greater vigilance to guard against excessive or inappropriate prescribing'. If these recommendations are followed, the UK might move to a system like that in the Republic of Ireland, where certain drugs may be prescribed only by specialists. I suspect that, if such prescribing restrictions are viewed as ways to reduce spending on new products (which tend to be costlier than old ones) the recommendations might win support from the Department of Health. However, they may be resisted by doctors' organizations. The report could also strengthen the role of the National Institute for Clinical Excellence (NICE) which would presumably be responsible for reassessing products after their probationary period and recommending whether their licenses should be renewed and prescribing restrictions lifted. This need for support in implementation underlies the inherent toothlessness of House of Commons Committees, whose recommendations tend to be adopted only if they find powerful champions. I therefore suspect that the Committee's calls for reforming the MHRA will be resisted unless a major drug safety scandal forces action. However, if the Department of Health and NICE back the Committee's proposals for restricting the prescribing of new drugs, this could come into force. In the case of the calls for increased transparency for clinical trial results and for trial registration, several powerful groups are already forcing companies in this direction—the report simply adds to the groundswell. Drug companies are increasingly realizing that irresponsible publication practices can generate negative publicity, and are therefore responding to pressure from journal editors and regulatory authorities to clean up their act. They are also starting to realize that lack of diligence over publications could affect their profits, which usually provides the most powerful motive for change and might mean that some of the Committee's recommendations are enacted. Competing interests I am a co-author of Good Publication Practice for pharmaceutical companies and the EMWA guidelines on the role of medical writers in developing peer-reviewed publications.

Raising the quality of publications: Now we have GPP!

AbstractUntil recently, few guidelines were available to assist companies in publishing their clinical trials and, compared to other phases of research, the quality of publications and the processes by which publications are developed have not received much scrutiny. However, guidelines on Good Publication Practice (GPP) for pharmaceutical companies have just been published. These aim to raise the quality of publications and to encourage ethical and responsible publication practices. The GPP guidelines were designed to be used alongside existing guidelines such as those from the International Committee of Medical Journal Editors (ICMJE) and the CONSORT statement. These, and other documents relevant to preparing publications, are reviewed and recommendations for ways in which companies might improve the quality of their publications are proposed. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Good publication practice for pharmaceutical companies

SUMMARYGuidelines on Good Publication Practice (GPP) for pharmaceutical companies are presented. The aim of the guidelines is to ensure that clinical trials sponsored by pharmaceutical companies are published in a responsible and ethical manner. The guidelines cover companies' responsibility to endeavour to publish results of all studies, companies' relations with investigators, measures to prevent redundant or premature publication, methods to improve trial identification and the role of professional medical writers. Our aim in publishing the GPP guidelines, which are the first to be developed by and for those working on publications in the pharmaceutical industry, is to stimulate discussion between journals, investigators and trial sponsors and to provide guidance to those who seek it. We also hope that pharmaceutical companies and others involved in developing publications arising from sponsored clinical trials will endorse the guidelines.