Papers affected by misconduct: Erratum, correction or retraction?

 

This week, Retraction Watch drew attention to a case summary of a misconduct investigation by the Office of Research Integrity (ORI) into grants and publications by Carlo Spirli, an Assistant Professor of Medicine, Department of Digestive Diseases, Yale University. This was based on an investigation conducted by Yale University plus analysis by ORI, which is reported with commendable transparency.

The conclusions were stark:

“ORI found that Respondent engaged in research misconduct by knowingly, intentionally, or recklessly falsifying and/or fabricating data included in the following four published papers, two presentations, and three grant applications submitted for PHS funds”. Details of the fabricated material in each of these sources were listed.

I suspect this investigation has been going on for a while; I could find no publications by Dr Spirli since 2019. In response to this report, he will "exclude himself voluntarily for a period of four years beginning on March 28, 2023” from contracting or subcontracting (presumably applying for grants) or serving on US Public Health Service committees. Compared to a French case that I blogged about recently this is a rather more serious outcome, though it nevertheless attracted critical comment on Twitter, and it is less severe than the measures that respondents thought appropriate for misconduct in a recently published survey of Fellows of the National Science Foundation. See Table 5, here.

My focus, here, however, is on another feature, which is similar to the French case. The report concluded that “Respondent will request that the following papers be corrected or retracted”, and then listed three articles published in Hepatology, two from 2012, and another from 2013.

Two of these have already had an ‘erratum’ published in 2022 (more details in Appendix below).

This seems inappropriate for two reasons.

First, according to Elsevier best practice guidelines, ‘an erratum refers to a correction of errors introduced to the article by the publisher’, as opposed to a ‘corrigendum’, which is a correction made on request by the author. 

Dr Spirli has an old CV online dating from 2017, in which he states he is a member of the Editorial Board of Hepatology. One wonders if this influenced the Editor who agreed to listing these two corrections as ‘Erratum’.

Second, though, the other category of ‘Corrigendum’ (i.e. Correction) also seems inappropriate here. We all make mistakes – I’ve got corrections to some of my papers, even though I try to be careful. It is all too easy to upload the wrong figure or miscompute some values when submitting a paper. If the conclusions are not affected by the error, a Correction is appropriate. But where there is a repeated pattern of falsification of data, or evidence that figures have deliberately been manipulated to fit a narrative, then a correction is not appropriate. The accompanying statements for Spirli’s ‘errata’ (see Appendix below) state that the conclusions are not affected. But the ORI report states that there was ‘reckless falsification or fabrication’ of data. Why, we ask ourselves, would an author falsify or fabricate data? The answer is obvious – to make inconclusive, inconsistent or null findings publishable. If the findings were solid in showing a desired result, there would be no need to engage in fraud. And if an author has shown a repeated tendency to engage in fraud, how can we trust the other data in their papers?

So this is a plea to ORI, CNRS, and other institutions, as well as editors, to start being more robust about the need for retraction of articles when misconduct has been demonstrated. Trying to ‘correct’ fraudulent articles is like trying to cut out a bad section from a rotting fish. The whole thing needs to be thrown away if you want to get rid of the stink.

Appendix

May 4 2022, Erratum to Spirli et al (2012a), Hepatology 2012;56:2363-74. doi: 10.1002/hep.25872

In reference to Spirli et al.,[1] we have become aware of possible errors in Figures 4C, and 5 A, B, and C. Forensic analysis concluded that in Figure 4C, the Actin blot appears to have been spliced and replicated. Therefore, the readings of CC3 as an index of apoptosis induced by Sorafenib are inconclusive. In Figure 5A, splicing is also present in Figure 5A (lane 1 and 12) and 5B (lane 12). These figures intend to show the paradoxical effect of Sorafenib on B-Raf and Raf-1 activity in WT and PC2-defective cells. The phenomenon remains valid, as shown in supplementary Figure 5, where exposure to Raf265, a Raf inhibitor with similar mechanism of Sorafenib generated a similar paradoxical effect. In Figure 5C there is a splice between lines 4 and 6 (effect of the higher concentration-10 μM- sorafenib in PKI treated cells). However, the observation that inhibition of cAMP/PKA with PKI prevents the paradoxical effect of Sorafenib on pERK and proliferation as shown in Figure 6 remains valid and is consistent with the in vivo finding. We believe that within the above limitations, the results and interpretation of the paper remain valid.

In addition to the four problematic figures (‘possible errors’) noted here, the ORI report mentions problems with Figures 3 and 6.

April 17 2022, Erratum to Spirli et al (2012b), Hepatology 2012;55(3):856-68. doi:10.1002/hep.24723

In reference to Spirli et al.,[1] we have become aware of an error in Figure 6A. This figure is intended to show that ER Calcium depletion (in this case using thapsigargin, an inhibitor of SERCA, the pump that allows ER Calcium entry) results in activation of the ERK pathway. The blot shows an example of Western blots from which the averages between phosphorylated ERK and total ERK shown in the bar graphs are then calculated. Forensic analysis concluded that Figure 6A contains lines seemingly duplicated for re-use in separate groups, as the bottom line 1–3 appears the same as lines 4–6. As such this figure should be considered erroneous (or falsified). However, reducing ER Calcium by another mean (chelation by TPEN) still increases ERK phosphorylation, and thus the results and interpretation of the paper remain valid.

17 June 2022, Retraction of Spirli et al (2015), Hepatology 2015 Dec;62(6):1828-39. doi: 10.1002/hep.28138.

The retraction has been agreed upon due to recently verified concerns regarding data authenticity rendering the conclusions uncertain. Several figures included in the article were found to have been falsified.

One can see from the ORI report that this one had so many figure manipulations that it was beyond help. It is the only paper in the report that had been flagged (by an anonymous commenter) on PubPeer.

 

Finally - please note that I welcome civil and on-topic comments, but they may take a while to appear, as comments are moderated to prevent spam.

 

When there are no consequences for misconduct: Parallels between politics and science

 

Gustave Doré: Illustration for Paradise Lost

(Updated 17 Dec 2022) 

As children, we grow up with stories of the battle between good and evil, but good ultimately triumphs. In adulthood, we know things can be more complicated: bad people can get into positions of power and make everyone suffer.  And yet, we tell ourselves, we have a strong legal framework, there are checks and balances, and a political system aspires to be free and fair.

 

During the last decade, I started for the first time to have serious doubts about those assumptions. In both the UK and the US, the same pattern is seen repeatedly: the media report on a scandal involving the government or a public figure, there is a brief period of public outrage, but then things continue as before.

 

In the UK we have become accustomed to politicians lying to Parliament and failing to correct the record, to bullying by senior politicians, and to safety regulations being ignored.  The current scandal is a case of disaster capitalism where government cronies made vast fortunes from the Covid pandemic by gaining contracts for personal protective equipment – which was not only provided at inflated prices, but then could not be used as it was substandard.

 

These are all shocking stories, but even more shocking is the lack of any serious consequences for those who are guilty. In the past, politicians would have resigned for minor peccadilloes, with pressure from the Prime Minister if need be. During Boris Johnson’s premiership, however, the Prime Minister was part of the problem. 

 

During the Trump presidency in the US, Sarah Kendzior wrote about “saviour syndrome”  - the belief people had that someone would come along and put things right. As she noted: “Mr. Trump has openly committed crimes and even confessed to crimes: What is at stake is whether anyone would hold him accountable.” And, sadly, the answer has been no.

 

No consequences for scientific fraud

So what has this got to do with science?  Well, I get the same sinking feeling that there is a major problem, everyone can see there's a problem, but nobody is going to rescue us. Researchers who engage in obvious malpractice repeatedly get away with no consequences.  This has been a recurring theme from those who have exposed academic papermills (Byrne et al., 2021) and/or reported manipulation of figures in journal articles (Bik et al., 2016).  For instance, when Bik was interviewed by Nature, she noted that 60-70% of the 800 papers she had reported to journals had not been dealt with within 5 years. That matches my more limited experience; if one points out academic malpractice to publishers or institutions, there is often no reply. Those who do reply typically say they will investigate, but then you hear no more.

 

At a recent symposium on Research Integrity at Liverpool Medical Institution*, David Sanders (Purdue University) told of repeated experiences of being given the brush-off by journals and institutions when reporting suspect papers. For instance, he reported an article that had simply recycled a table from a previous paper on a different topic. The response was “We will look into it”. “What”, said David incredulously, “is there to look into?”. This is the concern – that there can be blatant evidence of malpractice within a paper, yet the complainant is ignored. In this case, nothing happened. There are honorable exceptions, but it seems shocking that serious and obvious errors in work are not dealt with in a prompt and professional manner.

 

At the same seminar, there was a searing presentation by Peter Wilmshurst, whose experiences of exposing medical fraud by powerful individuals and organisations have led him to be the subject of numerous libel complaints.  Here are a few details of two of the cases he presented:

 

Paolo Macchiarini:  Convicted in 2022 of causing bodily harm with an experimental transplant of a synthetic windpipe that he performed between 2011-2012.  Wilmshurst noted that the descriptions of the experimental surgery in journals were incorrect. For a summary see this BMJ article.   A 2008 paper by Macchiarini and colleagues is still published in the Lancet, despite demands for it to be retracted. 

 

Don Poldermans: An eminent cardiologist who conducted a series of studies on perioperative betablockers, leading them to be recommended in guidelines from the European Society of Cardiology,  whose task force he chaired. A meta-analysis challenged that conclusion, showing mortality increased; an investigation found that work by Poldermans had serious integrity problems, and he was fired. Nevertheless, the papers have not been retracted. Wilmshurst estimated that thousands of deaths would have resulted from physicians following the guidelines recommending betablockers.

 

The week before the Liverpool meeting, there was a session on Correcting the Record at AIMOS2022.  The four speakers, John Loadsman (anaesthesiology), Ben Mol (Obstetrics and Gynecology), Lisa Parker (Oncology) and Jana Christopher (image integrity) covered the topic from a range of different angles, but in every single talk, the message came through loud and clear: it’s not enough to flag up cases of fraud – you have to then get someone to act on them, and that is far more difficult than it should be.

 

And then on the same day as the Liverpool meeting, Le Monde ran a piece about a researcher whose body of work contained numerous problems: the same graphs were used across different articles that purported to show different experiments, and other figures had signs of manipulation.  There was an investigation by the institution and by the funder, Centre National de la Recherche Scientifique (CNRS), which concluded that there had been several breaches of scientific integrity. However, it seems that the recommendation was simply that the papers should be “corrected”.

 

Why is scientific fraud not taken seriously?

There are several factors that conspire to get scientific fraud brushed under the carpet.

1.     Accusations of fraud may be unfounded. In science, as in politics, there may be individuals or organisations who target people unfairly – either for personal reasons, or because they don’t like their message. Furthermore, everyone makes mistakes and it would be dangerous to vilify researchers for honest errors. So it is vital to do due diligence and establish the facts. In practice, however, this typically means giving the accused the benefit of the doubt, even when the evidence of misconduct is strong.  While it is not always easy to demonstrate intent, there are many cases, such as those noted above, where a pattern of repeated transgressions is evident in published papers – and yet nothing is done.  

2.     Conflict of interest. Institutions may be reluctant to accept that someone is fraudulent if that person occupies a high-ranking role in the organisation, especially if they bring in grant income. Worries about reputational risk also create conflict of interest. The Printeger project is a set of case studies of individual research misconduct cases, which illustrates just how inconsistently these are handled in different countries, especially with regard to transparency vs confidentiality of process. It concluded “The reflex of research organisations to immediately contain and preferably minimise misconduct
cases is remarkable”.

3.     Passing the buck. Publishers may be reluctant to retract papers unless there is an institutional finding of misconduct, even if there is clear evidence that the published work is wrong. I discussed this here.  My view is that leaving flawed research in the public record is analogous to a store selling poisoned cookies to customers – you have a responsibility to correct the record as soon as possible when the evidence is clear to avoid harm to consumers. Funders might be expected to also play a role in correcting the record when research they have funded is shown to be flawed. Where public money is concerned, funders surely have a moral responsibility to ensure it is not wasted on fraudulent or sloppy research. Yet in her introduction to the Liverpool seminar, Patricia Murray noted that the new UK Committee on Research Integrity (CORI) does not regard investigation of research misconduct as within its purview.  

4.     Concerns about litigation. Organisations often have concerns that they will be sued if they make investigations of misconduct public, even if they are confident that misconduct occurred. These concerns are justified, as can be seen from the lawsuits that most of the sleuths who spoke at AIMOS and Liverpool have been subjected to.  My impression is that, provided there is clear evidence of misconduct, the fraudsters typically lose libel actions, but I’d be interested in more information on that point.

 

 

Consequences when misconduct goes unpunished

 

The lack of consequences for misconduct has many corrosive impacts on society. 

 

1.     Political and scientific institutions can only operate properly if there is trust. If lack of integrity is seen to be rewarded, this erodes public confidence. 

 

2.     People depend on us getting things right. We are confronting major challenges to health and to our environment. If we can’t trust researchers to be honest, then we all suffer as scientific progress stalls.  Over-hyped findings that make it into the literature can lead subsequent generations of researchers to waste time pursuing false leads.  Ultimately, people are harmed if we don’t fix fraud.

 

3.     Misconduct leads to waste of resources. It is depressing to think of all the research that could have been supported by the funds that have been spent on fraudulent studies.

 

4.     People engage in misconduct because in a competitive system, it brings them personal benefits, in terms of prestige, tenure, power and salary. If the fraudsters are not tackled, they end up in positions of power, where they will perpetuate a corrupt system; it is not in their interests to promote those who might challenge them.

 

5.     The new generation entering the profession will become cynical if they see that one needs to behave corruptly in order to succeed. They are left with the stark choice of joining in the corruption or leaving the field.

 

 

What can be done?

 

There’s no single solution, but I think there are several actions that are needed to help clean up the mess.

 

1.     Appreciate the scale of the problem.

When fraud is talked about in scientific circles, you typically get the response that “fraud is rare” and “science is self-correcting”.  A hole has been blown in the first assumption by the emergence of industrial-scale fraud in the form of academic paper-mills . The large publishers are now worried enough about this to be taking concerted action to detect papermill activity, and some of them have engaged in mass retractions of fraudulent work (see, e.g. the case of IEEE retractions here). Yet, I have documented on PubPeer numerous new papermill articles in Hindawi special issues appearing since September of this year, when the publisher announced it would be engaging in retraction of 500 papers. It’s as if the publisher is trying to clean up with a mop while a fire-hose is spewing out fraudulent content.  This kind of fraud is different from that reported by Wilmshurst, but it illustrates just how slow the business of correcting the scientific record can be – even when the evidence for fraud is unambiguous. 

Publishers trying to mop up papermill outputs

 

Yes, self-correction will ultimately happen in science, when people find they cannot replicate the flawed research on which they try to build. But the time-scale for such self-correction is often far longer than it needs to be.  We have to understand just how much waste of time and money is caused by reliance on a passive, natural evolution of self-correction, rather than a more proactive system to root out fraud.  

 

2.     Full transparency

There’s been a fair bit of debate about open data, and now it is recognised that we also need open code (scripts to generate figures etc.) to properly evaluate results. I would go further, though, and say we also need open peer review. This need not mean that the peer reviewer is identified, but just that their report is available for others to read. I have found open peer reviews very useful in identifying papermill products.

 

3.     Develop shared standards

Organisations such as the Committee on Publication Ethics (COPE) give recommendations for editors about how to respond when an accusation of misconduct occurs.  Although this looks like a start in specifying standards to which reputable journals should adhere, several speakers at the AIMOS meeting suggested that COPE guidelines were not suited for dealing with papermills and could actually delay and obfuscate investigations. Furthermore, COPE has no regulatory power and publishers are under no obligation to follow the guidelines (even if they state they will do so).

 

4.     National bodies for promoting scientific integrity

The Printeger project (cited above) noted that “A typical reaction of a research organisation facing unfamiliar research misconduct without appropriate procedures is to set up ad hoc investigative committees, usually consisting of in-house senior researchers…. Generally, this does not go well.”

In response to some high-profile cases that did not go well, some countries have set up national bodies for promoting scientific integrity. These are growing in number, but those who report cases to them often complain that they are not much help when fraud is discovered – sometimes this is because they lack the funding to defend a legal challenge. But, as with shared standards, this is at least a start, and they may help gather data on the scale and nature of the problem.  

 

5.     Transparent discussion of breaches of research integrity

Perhaps the most effective way of persuading institutions, publishers and funders to act is by publicising when they have failed to respond adequately to complaints.  David Sanders described a case where journals and institutions took no action despite multiple examples of image manipulation and plagiarism from one lab.  He only got a response when the case was featured in the New York Times.

Nevertheless, as the Printeger project noted, relying on the media to highlight fraud is far from ideal – there can a tendency to sensationalise and simplify the story, with potential for disproportionate damage to both accused and whistleblowers. If we had trustworthy and official channels to report suspected research misconduct, then whistleblowers would be less likely to seek publicity through other means.

 

6.     Protect whistleblowers

In her introduction to the Liverpool Research Integrity seminar, Patricia Murray noted the lack of consistency in institutional guidelines on research integrity. In some cases, the approach to whistleblowers seemed hostile, with the guidelines emphasising that they would be guilty of misconduct if they were found to have made frivolous, vexatious and/or malicious allegations. This, of course, is fair enough, but it needs to be countered by recommendations that allow for whistleblowers who are none of these things, who are doing the institution a service by casting light on serious problems. Indeed, Prof Murray noted that in her institution, failure to report an incident that gives reasonable suspicion of research misconduct is itself regarded as misconduct.  At present, whistleblowers are often treated as nuisances or cranks who need to be shut down. As was evident from the cases of both Sanders and Wilmshurst, they are at risk of litigation, and careers may be put in jeopardy if they challenge senior figures.

 

7.     Changing the incentive structure in science

It’s well-appreciated that if you really want to stop a problem, you should understand what causes it and stop it at source. People do fraudulent research because the potential benefits are large and the costs seem negligible.  We can change that balance by, on the one hand having serious and public sanctions for those who commit fraud, and on the other hand, rewarding scientists who emphasise integrity, transparency and accuracy in their work, rather than those that get flashy, eyecatching results.

 

I'm developing my ideas on this topic and I welcome thoughts on these suggestions. Comments are moderated and so do not appear immediately, but I will post any that are on topic and constructive.  

Update 17th December 2022  

Jennifer Byrne suggested one further recommendation, as follows:

To change the incentive structure in scientific publishing. Journals are presently rewarded for publishing, as publishing drives both income (through subscriptions and/or open access charges) and the journal impact factor. In contrast, journals and publishers do not earn income and are not otherwise rewarded for correcting the literature that they publish. This means that the (seemingly rare) journals that work hard to correct, flag and retract erroneous papers are rewarded identically to journals that appear to do very little. Proactive journals appear to represent a minority, but while there are no incentives for journals to take a proactive approach to published errors and misinformation, it should not be surprising that few journals join their efforts. Until publication and correction are recognized as two sides of the same coin, and valued as such, it seems inevitable that we will see a continued drive towards publishing more and correcting very little, or continuing to value publication quantity over quality.

 

Bibliography 

I'll also add here additional resources. I'm certainly not the first to have made the points in this post, and it may be useful to have other articles gathered together in one place.  

 

Besançon, L., Bik, E., Heathers, J., & Meyerowitz-Katz, G. (2022). Correction of scientific literature: Too little, too late! PLOS Biology, 20(3), e3001572. https://doi.org/10.1371/journal.pbio.3001572   

 

Byrne, J. A., Park, Y., Richardson, R. A. K., Pathmendra, P., Sun, M., & Stoeger, T. (2022). Protection of the human gene research literature from contract cheating organizations known as research paper mills. Nucleic Acids Research, gkac1139. https://doi.org/10.1093/nar/gkac1139 

 

Christian, K., Larkins, J., & Doran, M. R. (2022). The Australian academic STEMM workplace post-COVID: a picture of disarray. BioRxiv. https://doi.org/10.1101/2022.12.06.519378 

 

Lévy, R. (2022, December 15). Is it somebody else’s problem to correct the scientific literature? Rapha-z-Lab. https://raphazlab.wordpress.com/2022/12/15/is-it-somebody-elses-problem-to-correct-the-scientific-literature/ 

 

Research misconduct: Theory & Pratico – For Better Science. (n.d.). Retrieved 17 December 2022, from https://forbetterscience.com/2022/08/31/research-misconduct-theory-pratico/   

Star marine ecologist committed misconduct, university says. (n.d.). Retrieved 17 December 2022, from https://www.science.org/content/article/star-marine-ecologist-committed-misconduct-university-says  

Additions on 18th December: Yet more relevant stuff coming to my attention! 

 

Naudet, Florian (2022) Lecture: Busting two zombie trials in a post-COVID world.   

 

Wilmshurst, Peter (2022) Blog: Has COPE membership become a way for unprincipled journals to buy a fake badge of integrity?

 *Addition on 20th December

Liverpool Medical Institution seminar on Research Integrity: The introduction by Patricia Murray, talk by Peter Wilmshurt, and Q&A are now available on Youtube.

And finally.... 

A couple of sobering thoughts:

 

Alexander Trevelyan on Twitter noted  a great quote from the anonymous @mumumouse (author of Research misconduct blogpost above): “To imagine what it’s like to be a whistleblower in the science community, imagine you are trying to report a Ponzi scheme, but instead of receiving help you are told, nonchalantly, to call Bernie Madoff, if you wish." 

 

Peter Wilmshurst started his talk by relaying a conversation with Patricia Murray in the run-up to his talk. He said he planned to talk about the 3 Fs, fabrication, falsification and honesty.

 To which Patricia replied, “There is no F in honesty”. 

(This may take a few moments to appreciate).