Is the relationship between industry and randomised controlled trials (RCTs) too cosy? Or instead, is it a vital relationship that can help drive improvements and innovation within the field? Maybe it is somewhere in between the two. Spinal News International asks four physicians to give their take on this important question.
Jacques Müller-Broich (Bonn, Germany)
Being at three major university hospitals in Germany and having taken part in a number of randomised controlled trials (RCTs) sponsored by the industry, as well as being principal investigator at both industry-sponsored RCT’S but also several investigator initiated trials (IITs), it has always been an awkward feeling of sitting between the chairs. On one hand, taking the opportunity of paid contract research to conduct a scientific study with the goal of certifying for example a specific medical product and also a scientific publication with which one could advance their academic career by gathering impact factor points. On the other hand, there were clearly defined economic targets by the industry which had to be respected if one would be given the study and so the liberty of science was not so free any more. Still, holding the position of principal investigator made it possible to use influence on these working relationships with the industry partners to set additional scientific goals and co-targets.
Clearly mischief is possible in these relationships between industry and medical personnel, much as it is everywhere where people are working together, but I think it is also a very much needed opportunity in order to plan, execute and finish scientific studies at an academic hospital setting on a high scientific level. The academic institutions in many countries today do not have the financial and personnel resources in order to support a multitude of alleged neutral IITs. So many modern treatments or medical products would not have been available today if the RCTs were not financed by the industry.
There is definitely a great need for industry-sponsored RCTs, but both the industry and the academic research community need to understand that they have to meet high scientific and moral standards. It has to be a partnership on a par with each other. Research, data and finances of industry and investigators have to be transparent and the ethics committees and medical boards of the respective academic institutions, and government bodies have to take their control function seriously. The relationship between researchers and industry is definitely a motor of science and there is nothing to object to when all the rules of good clinical practice are closely followed.
Brian Fiani (Weill Cornell Medicine/NewYork-Presbyterian Hospital, New York, USA)
Conflict of interest is defined as a scenario where two or more parties may influence each other. Particularly in medicine, the concept of “conflict of interest” is frequently discussed when it comes to research studies. Often, randomised controlled trial (RCT) studies require large budgets which can only be supported by institutions, product donation, or funding from industry manufacturers. Concerns exist about whether the funding is ethical and if it generates a conflict.
As predicted, conflict of interest between industry and RCTs might be just as influential as expected. Certainly a centre of controversy, many believe that collaboration with companies who provide funding may influence biases. Investigations show that there is an associated difference in outcomes when comparing commercially-funded RCTs versus those without industry funding. Some studies identify positive trial conclusions and more frequent statistically significant results in the industry-supported RCTs. Over-interpretation of trial results is often cited as a possible reason. Another considerable conflict of interest is if the principal investigators have financial ties which could be independently associated with positive clinical results.
It is important to consider publication of the potentially biased results as well. Studies have shown that industry-supported RCTs are published more frequently than independently funded trials. Additionally, the publications of industry-supported RCTs have shown statistically to have higher impact factors. One may question if generous funding helps create better trials and therefore produce better publications or if industry-related factors are involved. Regardless, when it comes to disclosures, transparency is critical for the reliability of evidence-based medicine studies.
Spinal News International recently ran a poll asking physicians whether or not there was too much of a conflict of interest between industry and RCTs. The results were as follows:
Aaron Buckland (Melbourne Orthopaedic Group, Melbourne, Australia):
I believe the balance is about right at present. There is a difference between innovation and real-world data and demonstrating value however.
Randomised controlled trials (RCTs) are required for bringing new products to market, and without industry involvement and commercialisation ability, innovation would stifle. Industry-sponsored trials are often very well structured to demonstrate a difference (if one exists), by being much more selective in their inclusion criteria, and by removing factors that may give a ceiling effect to treatment. These should give the most ‘pure’ analysis of the device or technique’s efficacy, but may be seen to bias toward a positive outcome (false positive). The key in these industry-sponsored studies is that data analysis and interpretation should be assessed at ‘arm’s length’ to ensure data integrity and accurate, unbiased analysis and reporting. Currently this occurs by third party Contract Research Organisations.
Non-industry funded (including government funded) RCTs typically include a more heterogeneous group of patients, and often exhibit the opposite phenomenon, whereby there is a bias toward the null hypothesis. These studies serve a different purpose in my view, that is more applicable to demonstrating safety of the prosthesis/technique in a real-world environment, and when considering the cost utility of the intervention. There exists a heavy bias from government and insurance payers to invest in studies that would prove a null hypothesis in order to contain costs.
While RCTs may be the gold standard, it is often not possible to ethically perform these in the setting of surgical procedures, and we cannot rely solely on these studies to form our evidence base. Physicians need to understand how to interpret these studies, particularly in their biases, and to understand the delicate balance between innovation and public safety.
Issada Thongtrangan (Microspine, Phoenix, USA):
Randomised controlled trials (RCTs) are considered to represent the gold standard of scientific studies and paved the way for evidence-based medicine (EBM). RCTs are expensive and are mainly performed by the industry nowadays. Despite the strong focus on RCTs and EBM that could be witnessed in the last 20 years, approximately 50% of all medical therapies are still performed without class I evidence nowadays.
I believe there is too much conflict of interest between the authors and the industry despite full disclosure. It would be more neutral if the studies conduct by a third party, but it will be very difficult unless they have research funding to do so.
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