Research and Development
Research and development is the first stage in getting a product to a patient. Public, private or a mixture of public and private investment supports the development of medicines, medical devices and other healthcare technologies. Regulations vary around the world about what kind of evidence is required to get a product onto the market. Medicines, for example, must undergo studies and trials to determine their benefits and harms to ensure that they are safe to use. Other health care products, such as medical devices, require a less robust standard of evidence to allow them onto the market.
The main interaction at this stage is between companies manufacturing or marketing the product, researchers, contract research organisations (CROs) and of course, study or trial participants. Companies may fund academic researchers at universities and CROs to design, run and then report the study or trial results.
However, this interaction is at risk of conflicts of interest that can encourage actors to abuse their positions. Both researchers and CROs receive funding from companies that have an interest in the randomised controlled trials and other studies showing the benefits of their products. CROs may want to get further work, and therefore funding, from the companies. Researchers, as well as wanting further work from the companies, may have an academic interest in the results being positive – particularly if they have dedicated their careers to studying a particular area.
These particular conflicts may lead researchers, CROs or companies to under-report the negative findings of trials/studies or select a study design that will show the product in the best possible light, thereby abusing their entrusted power as research investigators. This has serious repercussions as medical knowledge that forms the basis of diagnosis and treatment in healthcare will be compromised by biased studies. Healthcare providers rely on this knowledge to offer patients the best treatments, while patients depend on this information to make choices about the type of care they want.
This is in contrast to the Declaration of Helsinki, first adopted in 1964 and having undergone seven revisions since, a widely recognised source of ethical guidance for biomedical research. The Declaration states the need to disseminate research results, including negative and inconclusive studies, and for all studies to be publicly registered, to make it harder for negative and unethical studies to go unnoticed and unchallenged.
Other companies and groups involved in the research process such as universities and journals, gatekeepers of medical knowledge, are also at risk of conflicts of interests and bribery. This also applies to journalists and other commentators on the research findings, for example experts, professional and patient groups, who may subvert the interpretation of the evidence to the public.
There is a particular risk that funders may exploit patients involved in clinical trials in low-and middle-income countries, abusing their positions as providers of safe, ethical trials to produce effective products. One key issue is that trial participants may not be able to give fully informed consent. In countries where there are issues with access to healthcare, some experts say that patients are unable to give genuine consent as turning down clinical trial participation is the equivalent of turning down treatment. Other issues include companies not obtaining fully informed consent, as the patients they target sign up to trials without fully understanding the described risks, and that patients are offered inadequate post trial access to treatment.
“What happens in clinical trials is not that you make up the results, it’s that you plan a trial that will get you the result you want, and so you basically move the goalposts. To be honest to me that's a softer version of corruption and one that is difficult to identify. In some ways it’s worse than the straight fabrication of data in preclinical work because it's insidious and it actually affects people directly.”
— Ivan Oransky - Vice President and Global Editorial Director, MedPage Today; Co-founder, Retraction Watch
Abuse of research funding systems
Research budgets from public and philanthropic funds are limited, meaning there is intense competition to attract and receive grants. Many countries have a well-defined methodology or points system to determine who gets that money. However, despite this apparent transparency, the system is open to multiple types of corruption, with resulting distortions to health research priorities.
Running studies generates sizeable income for universities and can fund departments for many years. There is pressure on academics to raise these funds given that public funding has significantly decreased. Applications from researchers for such funds may be spun and may contain an overly positive interpretation of studies conducted so far, in order to increase the chance of success. This potentially diverts money from other areas of research.
Without robust management of conflicts of interest, judges on panels deciding whom gets research funding may decide to give grants to friends, colleagues or reject grants from competitors – which in turn has a negative impact on health research.
Once the grant has been awarded, there is a risk that it may not be used for the reasons it was awarded. It may be used to fund different research activities within the institution, including those that have previously been rejected, or acquire equipment and upgrade the research facilities. Whilst this may be down to mismanagement rather than straightforward corruption, the boundaries are blurred.
Improper trial/study design
Researchers may select certain patients who are more likely to lead to a satisfactory result, by setting strict inclusion and exclusion criteria that are not aligned with the wider community or the patient constituency for which the product is intended. The danger of improper design in randomised controlled trials and other studies, is that the medical knowledge generated does not reflect the people who are using a particular product, so they may be getting suboptimal treatment.
Seeding trials are clinical trials designed by pharmaceutical companies to appear as if they answer a scientific question but primarily fulfilling marketing objectives, encouraging the use and unapproved use of their products. In particular, seeding trials allow the supplier to put its product in the hands of practising doctors. The existence of such studies has long been suspected, but published information about them has been limited. The failure to disclose the true objectives of the trial to patients, investigators, or institutional review board members is not in the best interests of patients or the medical profession, and is an abuse of the entrusted power pharmaceutical companies have to research and produce needed medicines.
Improper trial/study conduct
Before a randomised controlled trial or other study gets the go ahead, an ethics committee needs to approve it. Ethics committees may be private, part of a university, a national agency, or a local public committee.
In the case of private ethics committees, they may be run as a business. There is a risk that because they rely on a direct financial transaction, they may not want to turn down a study and put off other organisations coming to them in the future for ethical approval.
Similarly, university ethics committees may have a conflict of interest if the university relies on funding from a study or trial or the members of the committee are colleagues of the applicants. The risk of personal connections constituting conflicts of interest also applies to other types of ethics committees.
Research misconduct by academics and investigators may also occur. This may come in the form of fabricating data, falsifying or manipulating results and processes, and plagiarising ideas, words and results. For example, in terms of manipulating results researchers can substitute surrogate end points for true clinical endpoints, or may selectively analyse results so negative findings are hidden. If the true findings of a trial/study are obscured healthcare providers will be unaware of the risks of dispensing or using the product and patients will be put at unnecessary risk.
Misleading dissemination of trials/studies
There are a number of ways for individuals and groups to misleadingly disseminate randomised controlled trials and other studies. One way of doing this is to publish positive studies and not negative studies. Alternatively, researchers may omit discovered harms and overstate the benefits of a treatment, technology or way of delivering a service.
But ways of subverting the medical evidence base may be more subtle. Trials/studies may be misleadingly disseminated via guest authorship – when leading researchers are paid to be authors of an article that they didn’t write or for a study that they didn’t conduct. Instead, professional ghost writers briefed by the trial sponsor may write the article. Researchers may agree to this to enhance their reputation and increase their chances of getting future funding, which is often dependent on publications and past experience in scientific studies. For the trial sponsor, using acclaimed academics may lead to greater credibility and publicity for their published study.
Another issue comes in the role that journals have in disseminating research. Editors with links to manufacturers may suppress negative research findings and refuse to grant publication. Peer reviewers may misappropriate the contents of manuscripts or fail to disclose conflicts of interest that will have a bearing on the publication of research. All have an impact on the evidence on which medical treatments are based.
Finally, when research is published and covered by journalists with comments from experts, patient organisations and professional groups, there are further risks of conflicts of interest. For example, companies often pay journalists as expert media advisors on a particular treatment or service and ask them to sign confidentiality agreements. The journalist may then report on the ensuing publication without declaring any conflicts of interest.