A “RIAT Expression of Concern” is a letter to the editor that aims to publicly register a serious concern about a clinical trial. Serious concerns include evidence of under- or misreporting (e.g. incorrectly reporting trial results), evidence of serious trial design flaws (e.g. use of a comparator that prohibits a fair assessment of adverse events), and inadequate transparency (e.g. a lack of data sharing for a public health intervention). RIAT Expressions of Concern bring attention to these issues and call for the record to be corrected (for example, through an erratum). Such letters are a small but critical early step towards correcting errors in the published literature.
The RIAT Expressions of Concern Campaign actively tracks all RIAT Expressions of Concerns and demonstrates that serious issues like trial misreporting and inappropriate methods are widespread problems of concern to a large number of researchers worldwide who want to see the record corrected.
RIAT Expressions of Concern can be written by anyone wishing to correct the record through the RIAT initiative. RIAT Expressions of Concern may be authored by, with, or independently of the RIAT Support Center. Prior to submission to a journal, the RIAT Support Center facilitates a process of pre-submission peer review to ensure that at least one party external to the authors agrees with the bones of the authors’ allegations.
If you wish to write or suggest a RIAT Expression of Concern, contact us.
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2023-01 | MATISSE trial of bivalent RSV prefusion F protein–based (RSVpreF, ABRYSVO) in pregnant mothers. NCT04424316 – publication |
The article published in NEJM states that the incidence of preterm birth, an adverse event of special interest, was “similar” between vaccine and placebo group and that “No safety concerns were identified.” Peter Selley requested a correction to the article, noting that the incidence was 19% greater in the vaccine arm. |
Jun 7, 2023 Selley submitted an Expression of Concern
Aug 16, 2023 New England Journal of Medicine rejected Selley’s letter |
No. NEJM rejected the letter, stating, “Other letters have been received on this subject, and I think you will find your point of view adequately represented among those already accepted for publication.” |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2022-002 | Two trials comparing ablation vs. medication in treatment-naive, younger atrial fibrillation patients without heart failure and with time since atrial fibrillation onset of about 1 year; NCT03118518 & NCT02825979 – publication 1 & publication 2 |
Both trials had an unproven surrogate outcome as their primary outcome. Further, quality of life results for both trials were not interpretable due to flawed design in EARLY-AF FIRST and flawed analysis in STOP-AF FIRST. |
Feb 14, 2022 RIAT Expression of Concern
March 18, 2022 Communication from the Journal |
The Journal concluded that they found no indication for an Expression of Concern or other action. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2022-001 | Trial of quality of life (QoL) improvements with catheter ablation compared with medical therapy in patients with symptomatic atrial fibrillation; NCT02294955 – publication |
Trial did not prospectively specify its primary QoL outcome/timepoint, and misinterpreted its QoL result as a “clinically relevant” difference. |
Feb 14, 2022 RIAT Expression of Concern
Feb 15, 2022 Communication with the Journal |
The Journal indicated that the Expression of Concern did not receive a high enough priority rating from editorial staff to warrant publication. The authors have responded to the Editor asking if they plan to issue any corrections to the original publication; waiting for a response. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-012 | 6-month update to Pfizer SARS-CoV-2 vaccine safety and efficacy trial in adults; NCT04368728 – publication |
Inaccuracy of clinical trial flow diagram |
Dec 9, 2021 RIAT Expression of Concern
Dec 8, 2021 and onwards communication with the Journal: rejection letter from NEJM, author response to rejection letter, NEJM sent letter to the Editor, NEJM unable to comment on original authors’ contact details, reminder email to NEJM, initial email to NEJM Editor, email thread with NEJM Editor, case closed with NEJM Editor |
The Journal rejected the letter editors as they were no longer considering new submissions regarding that article. After communication with the Journal about whether or not they were going to issue a correction to the misreported trial, the Editor indicated that the original authors did account for the minor discrepancies their manuscripts and that NEJM did not intend to publish a correction to the article. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-008 | AstraZeneca SARS-CoV-2 vaccine safety and efficacy trial in adults; NCT04516746 – publication |
Trial results omitted key safety results Bri Dressen (trial participant) |
Nov 10, 2021 RIAT Expression of Concern
Nov 15, 2021 and onwards communication with the Journal |
The Editor rejected the letter due to limited space at the Journal. The author wrote back to the Editor asking if the Journal will be correcting the misreported trial. The Editor suggested the author contact the trial authors directly and offered to forward the author’s expression of concern to the manufacturer. It seems this has not yet happened. The discussion between the author at the Editor continues. The author was sent a settlement form from AstraZeneca’s proxy, Velocity Clinical Research. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-010 | Quality of life trial with catheter ablation compared with medical therapy in patients with symptomatic atrial fibrillation; NCT00911508 – publication |
Selective outcome reporting and lack of evidence supporting the abstract conclusion of “clinically important” quality of life improvements with catheter ablation. |
Oct 28, 2021 RIAT Expression of Concern | The Journal indicated that the Expression of Concern did not receive a high enough priority rating from editorial staff to warrant publication. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-009 | Indacaterol trial assessing its safety and efficacy for dyspnea and health status as patient-reported outcomes; NCT01068600 – publication |
Misreporting of serious adverse events |
Sep 24, 2021 RIAT Expression of Concern
Sep 27, 2021 Communication from the Journal |
The Editor rejected the letter as letters should be received less than six months after publication of the original work in question. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-011 | Two 12-week Indacaterol randomized controlled trials assessing its efficacy and tolerability in patients ≥40 years with chronic obstructive pulmonary disease; NCT01072448 and NCT01068600 – publication |
Misreporting of serious adverse events |
Sep 23, 2021 RIAT Expression of Concern
Oct 5, 2021 Communication from the Journal |
The Editors determined that they could not accept it for publication without offering the authors of the original manuscript a chance to respond, but due to the extensive length of time between the publication of the original article and the RIAT Expression of Concern, it was felt that this was a somewhat unreasonable expectation. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-007 | duloxetine trial for the treatment of depression in adults; publication |
Trial results were neither reported nor analyzed according to the study protocol Anisa Rowhani-Farid Kyungwan Hong RIAT Support Center |
Sep 2, 2021 RIAT Expression of Concern | The Editor rejected the letter due to limited space at the Journal. The authors wrote back to the Editor asking if the Journal will be correcting the misreported trial; we are waiting to hear back. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-005 | Fluoxetine trial for the Treatment of Depression in Children and Adolescents; publication | Discrepancies between the adverse events reported in the clinical study reports and the publication | Jul 19, 2021 RIAT Expression of Concern | The Editor of JAMA Psychiatry shared the Expression of Concern with the authors and after carefully evaluating the concerns raised, concluded that no action was necessary. |
| 2021-006 | Fluoxetine trial for the Treatment of Depression in Children and Adolescents; publication | Discrepancies between the adverse events reported in the clinical study reports and the publication | Jul 19, 2021 RIAT Expression of Concern | The Editors of the Journal of the American Academy of Child and Adolescent Psychiatry indicated that the letter does not provide sufficient information to investigate the concerns raised and so they requested more information – we are waiting a decision from Editors. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-004 | Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder Two Randomized Phase 3 Trials; NCT02333071 and NCT02338960 – publication | Concerns include missing data, changing endpoints, participant discontinuation rates, and adequacy of the journal’s peer-review process.
An independent re-analysis of trial conducted by Spielmans (2021) led to a response rejecting the issues raised from the original authors, Kingsberg et al. (2021). Spielmans (2021) responded with concern about the original authors’ response. Leonore Tiefer, Rosemary Basson, Susan Bewley, Lori Brotto, Lisa Cosgrove, Adriane Fugh-Berman, David Healy, Ellen Laan, Barbara Mintzes, Ray Moynihan, Cynthia A. Pearson, Diana Zuckerman |
Apr 19, 2021 RIAT Expression of Concern
Apr 23, 2021 Obstetrics & Gynecology rejects the letter. |
The Editor of Obstetrics & Gynecology rejected the letter and indicated that an Expression of Concern was not warranted. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-003 | BNT162b2 mRNA Covid-19 (Pfizer) vaccine trial (NCT04368728 – publication) and mRNA-1273 SARS-CoV-2 (Moderna) vaccine trial (NCT04470427 – publication) | Inconsistent and incomplete Conflicts of Interest Disclosures in publications | Feb 25, 2021 RIAT Expression of Concern | Waiting to hear back from the NEJM Editors. They decided not to publish the letter. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2021-001 | mRNA-1273 SARS-CoV-2 (Moderna) vaccine trial (NCT04470427 – publication) | Lack of data shared from Moderna Covid-19 vaccine trial
Anisa Rowhani-Farid, Kyungwan Hong, Peter Doshi (RIAT Support Center) |
Feb 15, 2021 RIAT Expression of Concern
Feb 26, NEJM rejects the letter |
The NEJM Editors decided not to publish the letter and engaged in a discussion about data sharing. The NEJM Editors directed us to contact the authors of the article directly; the RIAT team has asked them about their position on data sharing and they have indicated that the data are not yet ready to be shared. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2020-005 | BNT162b2 mRNA Covid-19 (Pfizer) vaccine trial (NCT04368728 – publication) | Selective reporting of results in Abstract and Research Summary of Pfizer vaccine report | Dec 19, 2020 RIAT Expression of Concern
Dec 30, 2020 NEJM rejects letter |
Partially. The NEJM editors corrected the Research Summary by eliminating the problematic section altogether but decided not publish the RIAT expression of concern, and did not modify the article Abstract. |
| 2021-002 | BNT162b2 mRNA Covid-19 (Pfizer) vaccine trial (NCT04368728 – publication) | Unavailability of data for Pfizer’s Covid-19 vaccine phase 3 study
Anisa Rowhani-Farid, Sarah Tanveer, Peter Doshi (RIAT Support Center team) |
Feb 17, 2021 RIAT Expression of Concern
Feb 18, 2021 NEJM rejects letter |
No. The NEJM editors decided not to publish our letter due to the limited correspondence space at the journal |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2020-004 | Quadrivalent human papillomavirus vaccine (Gardasil) trial V501-012 (NCT00092482 – publication) | Incomplete reporting of important methodological details and inaccurate description of the formulation that the control arms received
Florence Bourgeois, Peter Doshi, Kyungwan Hong, Tom Jefferson, Mark Jones, Haeyoung Lee, Anisa Rowhani-Farid, Larissa Shamseer, O’Mareen Spence (RIAT Support Center) |
Jul 27, 2020 RIAT Expression of Concern
Oct 12, 2020 Clinical and Vaccine Immunology (mSphere) accepts letter |
No, however the journal published the RIAT authors’ letter and the original authors’ response. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2020-003 | Quadrivalent human papillomavirus vaccine (Gardasil) trial V501-019 (a.k.a. FUTURE III) (NCT00090220 – publication) | Incomplete reporting of important methodological details and inaccurate description of the formulation that the control arms received
Peter Doshi, Kyungwan Hong, Tom Jefferson, Mark Jones, Anisa Rowhani-Farid (RIAT Support Center) |
July 26, 2020 RIAT Expression of Concern
July 31, 2020 Lancet rejects letter March 20, 2021 The Lancet publishes RIAT Expression of Concern and the authors’ response. |
No. Journal editors decided to contact the authors of the misreported trial to inform them of our concerns. The authors’ response as well as the RIAT Expression of Concern were published in the Lancet. The authors did not address the concerns that were raised. Waiting to hear back from the Lancet Editor to see if a response to the authors would be welcomed. |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2020-002 | Four Gardasil vaccine trials published in the New England Journal of Medicine (NCT00092521 – publication, NCT00092534 – publication, NCT00090285 – publication, NCT00365378 – publication) | Incomplete reporting of important methodological details and inaccurate description of the formulation that the control arms received
Peter Doshi, Tom Jefferson, Anisa Rowhani-Farid (RIAT Support Center) |
June 8, 2020 RIAT Expression of Concern
June 15 NEJM rejects letter |
No, the journal editors decided that they did not think a correction was necessary and decided not publish the expression of concern |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2020-001 | Trimethoprim-Sulfamethoxazole versus Placebo for Uncomplicated Skin Abscess (NCT00729937) | Trials results not reported according to protocol
Peter Doshi and Tom Jefferson (RIAT Support Center) |
January 17, 2020 RIAT Expression of Concern
January 28 Rejection from NEJM |
No. Despite the NEJM’s decision not to correct the article, the original trialists were willing to do so |
| Expression of Concern ID number | Trial(s) | What is the core concern, and who is raising it? | Timeline of key RIAT-related efforts and journal response | Correction to original article achieved? |
|---|---|---|---|---|
| 2019-001 | A randomized clinical trial evaluating plasma rich in growth factors (PRGF-Endoret) versus hyaluronic acid in the short-term treatment of symptomatic knee osteoarthritis. | Discrepancies among the protocol, final report and published article for main efficacy outcome
Luis Carlos Saiz Fernandez, Juan Erviti, Leire Leache, and Marta Gutiérrez-Valencia (Unit of Innovation and Organization, Navarre Health Service, Spain) |
September 27, 2019 RIAT Expression of Concern
Jan 6, 2020 journal agrees to publish RIAT authors’ letter March 2 Arthroscopy publishes RIAT authors’ letter and the original authors’ response March 6 RIAT authors detail problems with original authors’ response |
No however the journal published the RIAT authors’ letter and the original authors’ response |