Manuscript Submission and Review: Perspective of an Editor and Author Jim Neaton PubH 8400 December 7, 2016 Thank you for the invitation to be part of this clinical trials design workshop. I was asked to talk about how trial investigators adapt to new information that emerges during the conduct of a trial. My focus will be on new information that is external to the trial being done and not from the ongoing trial itself. This occurs often particularly in long-term studies.

Perspective of an Editor: How it Works Controlled Clinical Trials (now Clinical Trials) 25 Associate Editors (50 now); a Book Review Editor; and a 4 person Advisory Board Publisher: Elsevier Science (now Sage) 150 submissions per year 6 issues/year; 8 articles; 90 pages 2,052 subscribers; 528 institutional Impact factor: 1.86 (Stat Med 1.53, Biometrics 1.36)

Steps in the Process When a paper arrives: Editor reviews (rarely rejects) and assigns Associate Editor (AE). AE reviews and rejects or recommends 4 referees. Editorial Assistant contacts 2 referees to review paper. Referees submit review. Editor reviews and sends comments to AE. AE makes recommendation. Editor makes final decision and prepares letter to author. Accept unconditionally Accept provisionally Reject with invitation to resubmit Reject (sometimes with recommendation to a more appropriate journal)

For Provisional Acceptance and Reject with Invitation to Resubmit Author modifies paper and resubmits, reiterating each comment with point by point response. Editor reviews and sends to AE with recommendation (accept, reject, or back to referees). AE reviews and notifies Editor. If accepted, paper is copyedited and sent back to authors; otherwise reject letter or re-review by referees. Upon receipt of paper with copyedits made, paper is sent to publisher for typesetting. Publisher prepares galleys for author and Editor’s office. Publication (usually 3-4 months after galleys returned).

How it Really Works Editor beats the bushes for good papers (e.g., presentations at major meetings). Editorial Assistants regularly harass Editor, AEs and referees. Frequent hand-holding with authors.

Advice from Editor to Authors Spell-check your paper. State clearly the purpose of the paper. Be concise. Read papers in the journal to which you are submitting. Respond as requested – point by point to comments made by referee, AE and Editor. Respond quickly. Carefully review the galleys. Read conditions of submission and authorship responsibilities.

Perspective of an Author: Publishing the Results of a Clinical Trial – Which Journal? Top general medicine journals (impact factor) New England Journal of Medicine (59.6) Lancet (44.0) Journal of the American Medical Association (37.7) Annals of Internal Medicine (16.6) Specialty journals, examples in my area (impact factor) Circulation (17.0) Clinical Infectious Diseases (8.9) AIDS (4.4)

Publishing Results of a Clinical Trial: Some Tips Make sure trial is registered with clinicaltrials.gov (a legal requirement for most trials within 21 days of 1st enrollment; a requirement for publication for most journals). Review CONSORT guidelines for clinical trials, e.g., flow diagram and checklist (most journals require flow diagram and many ask authors to complete the checklist as part of submission) (www.consort-statement.org). Be prepared to provide each version of protocol and statistical analysis plan

See also N Engl J Med 2012; 367:1355-1360

Publishing Results of a Clinical Trial – More Tips Major trials are typically reviewed by 3-4 referees, one of whom is a statistician. Some journals (e.g., Lancet) guarantee peer review if protocol is submitted for review in advance (they also post a study abstract on their website). http://www.thelancet.com/protocol-reviews-list Protocol 11PRT/3028: INSIGHT Strategic Timing of AntiRetroviral Treatment [START] (NCT 00867048) Major medical journals have a “fast track” (call/email Editor or Associate Editor). Once accepted, there is an embargo imposed during which the contents of the paper cannot be shared. Best is if presentation and publication are done together. Major trials almost always have an accompanying editorial. Expect letters to the editor.

Not All Trials Are Published, But… Many clinical trials are conducted and not published (more common for industry funded than NIH-funded trials). However, results of clinical trials now have to be submitted to clinicaltrials.gov within 12 months of completion (this is very time-consuming). A movement is afoot to make raw data available for trials.

Some Recent Articles/Commentaries Gordon D et al (N Engl J Med 2013) – “less than two thirds of NHLBI-funded clinical trials…were published within 30 months of completion.” Devereaux PJ et al (N Engl J Med 2013) – “When it comes to trial, do we get what we pay for?” Get value for money when it comes to large trials with clinical endpoints. Krumholz HM et al (N Engl J Med 2016) – YODA project Drazen J (N Engl J Med 2016) – The importance and complexity of data sharing. Lo B and DeMets D (N Engl J Med 2016) – Incentives for clinical trialists to share data. Rockhold F et al (N Engl J Med 2016) – Data sharing a crossroads.