Magnifying glass over science: scientific publications forced to reconsider review processes

Publicação: 22 de July de 2020

The retraction of an article is foreseen in the protocols of renowned journals when some type of misconduct, fraud or error is detected

Until recently, almost no one had heard of Surgisphere, but that changed after a hundred experts contested the study that linked antimalarials to increased risk of death in patients with COVID-19

The New England Journal of Medicine and the magazine “The Lancet”, two of the most prestigious scientific publications in the field of medicine, were forced to withdraw studies related to COVID-19 and to reconsider their peer review procedures. An investigation by British newspaper “The Guardian” revealed that the American company Surgisphere, whose employees appear to include a science fiction writer and an adult content model, provided data for several studies on COVID-19, co-authored by its CEO. Three of the four authors in the study that suggested that chloroquine and hydroxychloroquine antimalarials may increase the risk of death for patients with COVID-19 portrayed the study, claiming that it does not guarantee the veracity of the data. The retraction of an article is foreseen in the protocols of renowned journals when some type of misconduct, fraud or error is detected

The epidemiologist who coordinates the Center for Data Integration and Knowledge for Health (CIDACS), of Fiocruz in Bahia, Dr. Maurício Barreto, points out that there is no doubt that this work is totally demoralized. Still according to him, the case is one of the strangest that he has seen in recent times with regard to terms of data use and, mainly, the ability to involve researchers from important institutions. The study was signed by Mandeep Mehra, from Brigham Women’s Hospital in Boston, Harvard University (USA), Frank Ruschitzka, from Zurich University Hospital, University of Zurich (Switzerland), Amit Patel, from the University’s Department of Bio-Engineering from Utah (USA), and Sapan Desai, surgeon and founder of Surgisphere. “The universities involved are traditional institutions that take great care of issues involving ethics and integrity, in addition to other topics. How can a work of this importance, whose debate on the use of chloroquine and hydroxychloroquine still persist, have passed through the scrutiny of these institutions and two of the most important scientific journals in the world?”, asks the CIDACS coordinator.

Many researchers expressed doubts about the work and raised questions about the methods used and the source of the data. But the big puzzle is: how does little known company suddenly acquire the information from almost 100 thousand patients, from more than 400 hospitals in the world. “Anyone working with data knows how difficult it is to obtain and extract information about patients from a hospital. Imagine more than 400. This sounded very strange in the community that deals with data”, reports Dr. Barreto. This generated a great conflict that triggered an entire investigation system on the origin of the data and that resulted in the retraction of the article due to Surgisphere’s lack of clarity on the copyrights of the data, as well as whether they were really real or created. For Dr. Barreto, this is the big question and there is no reason to believe that they had access to the data supposedly obtained.

The inconsistencies of the published study

Among the various inconsistencies of the study published in The Lancet, Dr. Barreto highlights the lack of clarity in demonstrating the source of the data. “This is a central, legal and ethical thing.” No personal or institutional data can be worked on by others without having all possible authorization systems”, he adds. According to the researcher, this leads to a very intense reflection: how the universities involved, the peer reviewers and the editors of two of the most important magazines in the world, accepted this. “For me, this is another major incongruity in the process”, he emphasizes. Professor Barreto also acknowledges analysis and methodological problems – this is an important part of the debate, but which could possibly be corrected by letter to the editors, amendments or discussions. Another unconsciousness cited by the epidemiologist concerns the cases of total deaths that occurred in the country (such as Australia) and the number reported in the article.

The biggest scientific scandal related to the COVID-19 pandemic caused the largest observational study with chloroquine, published in late March, to be removed. The work stated that the drug increased the risk of death for patients. The retraction of the two largest medical journals in the world revealed the risks of science made in haste, in an attempt to follow the speed of the new coronavirus. Furthermore, the fact that the study was portrayed does not imply that antimalarials have any well-established effect and their use remains unfounded, much less in a pre-symptomatic stage or mild symptoms. According to Dr. Barreto, the use of these drugs really remain without any evidence that they have an effect on patients with COVID-19, because so far, there is nothing serious published that proves this effect. Still according to him, the current studies were affected by the article that reported the toxicity and the effects of the drug on health and the increased risk of death in COVID-19 patients. “The point of the scientific community is that there is no evidence to justify the use of hydroxychloroquine or chloroquine at any stage of the disease. Most of the mild cases evolve without any complications, that is, administering these or other medications does not represent a cure, as they would improve anyway, it is what we call the placebo effect”, he points out.

Asked why a study of secondary data was given so much value that the World Health Organization (WHO) suspended clinical trials, Dr. Barreto argues that this was not a gross error, not least because the study was published in renowned journals, was signed by researchers from reputable universities and institutions, and obviously this created a great scientific impact. To him, the problem was the publication of the article. “The first reaction that was observed was caution, because if a study with almost 100 thousand people, with data collected from hospitals, shows that these drugs are causing adverse effects, it is already sufficient justification to suspend other studies, normal logic of clinical practice, since in clinical tests, two elements are central. On the one hand, the efficacy of the medication and on the other, safety. In other words, how much of an adverse effect the medication often has is the most important factor in a clinical decision – a medication can be very effective, but has many adverse effects – this balance between adverse and beneficial effects is what matters”, explains Dr. Barreto Also according to him, at the moment when there is evidence that the drug has adverse effects without having yet proven the beneficial effects, it is logical that the international scientific community and WHO should take a position of justifiable caution. “The problem lies in the fact that these data were generated in some way and reached scientific publications and, mainly, those of such an impact in which they were published”, he observes.

But are studies using data from Surgisphere portrayed in the “New England Journal of Medicine” and “The Lancet” in fact a disservice to science and fueling those who question science and the scientific process well done? In the opinion of Dr. Barreto there is no doubt that yes. “The retraction of scientific articles is not a new thing in science, some, for example, are due to the gross falsification of data that arrived in major journals. This is not the first study that reached the renowned journal and that used falsified data. When this occurs, the works are portrayed, the researchers involved are despised by the scientific community, especially if there was deception, and science continues; this represents a possibility of the scientific process that is linked to the integrity of scientific action. Making mistakes in science is possible, but one should not make mistakes intentionally”, he emphasizes. The CIDACS coordinator also recalls that this fact occurs in the course of a pandemic, where there is great tension and anxiety amongst the society, and that it has gained dramatic proportions, aggravated by the moment when there is a great debate between anti-science groups, groups that want to deny, demoralize, despise science, that is, justify the use of a medicine, without any scientific basis. And so, arguments are created, the possibility of falsification increases, science is put into disrepute, the entire scientific process is questioned.

Institutions should review their retraction processes

For Dr. Barreto, not only the journals and the WHO should review their retraction processes, but the Universities as well. The researcher admits that he would like to hear the parties involved to know what they are doing regarding what happened. The researcher demands a clear position from the Universities and hopes that they are carrying out internal investigations and that at some point they will manifest themselves. “I think that the entire scientific process needs to be reviewed. Of course, this should never have happened. First, Surgisphere could never do what it did. Second, researchers from large institutions should not have signed this scientific work, with data they did not know the source of. Worse, this is not being discussed. To me it is the most important issue, because journals are not the only ones responsible for covering the sieve of possibilities of lack of scientific integrity. The institutions must take care first. I think that this was not well discussed in this case and deserves an in-depth debate: what was the role of Universities involved in this process? Did Surgisphere’s data go through these Universities? These are issues that have not yet been clarified”, he weighs.

As for the WHO, Dr. Barreto believes that it doesn’t have to be a portraitist. In his opinion, the Organization took a correct step in suspending or recommending the suspension of clinical trials that were underway to protect patients. “I understand that anyone would have taken this attitude, since the work was presented to the scientific community in a highly credible magazine. All of this leads us to reflect on the fallibility of the Peer Review process. We need to think about how science can create alternatives, because one of the mainstays of the scientific process and scientific credibility is the Peer Review and at the moment when events like this happen, it evidences the fallibility of the system, demonstrating that there must really be changes in the adopted processes. Obviously, the Peer Review, in this phase of the pandemic, happens in an accelerated way and this has generated new possibilities of failures and, who knows, expanded these possibilities”, concludes Dr. Barreto

Positive aspects of the scientific process

Science has the ability to correct itself and that is why it is believed, unlike anti-science policy. This is an important fact. We take as an example the Surgisphere episode, when it was realized that there was an error, the process stopped. That is, with all the damaging effects, in several aspects that this work created, it also shows positive aspects of the scientific process. “It is a process that has errors, that can fail, but that at some point can be corrected. That’s something positive. Of course, it is necessary to make efforts to reduce the possibilities of failures as much as possible, because it fuels anti-science policies”, emphasizes the epidemiologist when saying that the case of Surgisphere shows how immensely anti-science groups have strengthened themselves by showing to the public the reverse justification and that people are being deceived by regular science”. Still according to the researcher, the case in question shows that similar facts cannot occur or need to be reduced, especially when they involve controversial, passionate themes, which evoke the general public and generate alarming proportions and gain such dimension.

“Science is a process that has certain characteristics and in this Surgisphere case has escaped normal characteristics. For example, there is a debate about the authors, who did not collaborate before and are not in the field of clinical, pharmacoepidemiology, but in areas distant from the issue of drugs or assessment of adverse effects. It is a very heterogeneous group and has no affinity with the topic. This is one of the oddities that arises and that should have been observed in the beginning”, points out Dr. Barreto He clarifies that during the pandemic many researchers have been mobilized and collaborated to carry out works that are outside their areas, but reminds that there are no specialists in the group on adverse effects or on more specific issues that the study demands. For him, this lack of clarity and these inconsistencies deserved attention and perhaps the article had not been published. “There are still puzzles to be clarified. The whole genesis of the process is in what happened, as well as in the origin of the data”, he reverberates. Finally, Dr. Barreto is categorical in stating that putting all the cards in the Peer Review or in the journals is not the way. “This is part of the process, it is part of the guilt and responsibility, but there are other elements to the story, of the responsibilities, that need to be investigated so that facts like this can be reduced, or become less frequent, and that are less likely to have repercussions and make publications around such important topics and journals”, he concludes.