Research Skills for the Modern Surgeon

Good clinical research practice demands that all research complies with the highest ethical code. Unfortunately, however, there are multiple examples of human rights abuses and exploitation of vulnerable groups in medical research. These include atrocities committed by Nazi doctors in concentration camps; trials where antibiotics were deliberately withheld from syphilis patients to facilitate observational studies, and experiments on American prison inmates recruited via coercion. Modern medical ethics evolved in response to such events. It originates from the Nuremberg Code: ten doctrines issued by the jurists involved in the “Doctors Trial” at Nuremberg. These principles advocate for the autonomy of participants and informed consent. The field of ethics has progressed from this time with the publication and subsequent revision of landmark guidelines including the Helsinki Declaration, the Belmont report and the Georgetown mantra. The overarching principles of ethical research include respect for autonomy, beneficence, non-maleficence and justice.

The Declaration of Helsinki states that “research must be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to the subject or to others.” The current norm is that all research involving patients, service users or volunteers (or their organs or tissues) is subject to independent review to ensure it meets a minimum ethical standard. Gaining approval from the relevant research ethics committee is a crucial step in conducting research and it is now a ubiquitous requirement for publication. However, this is not a one-off process and good practice demands ongoing respect for ethics in completing the project and disseminating the results.

The following seven principles have been proposed as requirements for ethical research:

The proposed project must be of value to society by enhancing the knowledge base regarding a specific disease or treatment, and hence contribute to an overall improvement in health. This ensures that finite research resources are maximized for social or scientific benefit.

The study design proposed must be feasible and scientifically robust to answer the specific research question and hence generate meaningful new information. To produce reliable and valid data, the methodology proposed must be appropriate with logical statistical techniques, including an adequate sample size. Those involved must have adequate experience to complete the project, including interpretation and dissemination of the results.

The purpose of inclusion/exclusion criteria is to meet the scientific goals of the study. However, these steps must also ensure that participation balances the risks and benefits of the study among different groups. Special consideration must be given to protect vulnerable groups including their capacity to provide informed consent.

For research to be considered ethical, benefits must be maximized while simultaneously minimizing any risks or harms. Overall, potential benefits must outweigh any risks including non-health risks.

Independent review via a Research Ethics Committee minimises the impact of any potential conflicts of interests those involved in the project may hold and provides social accountability.

Informed consent is pivotal in respecting the personal autonomy of participants. To provide valid informed consent potential participants must be provided with - and understand - information about the purpose, risks, benefits and alternatives to participation. They must be enabled to make a voluntary personal decision, free from any coercion. To this end, Participant Information Sheets discussing these issues should be provided, written in clear language, with opportunities to discuss and ask questions. Time between requesting participation and signing consent facilitates due consideration and prevents undue pressure.

While a study is in progress, ongoing respect for subjects involves informing them of their right to withdraw consent, at any time, without reason. Safeguarding privacy and maintaining the welfare of participants must remain priorities, with contingency planning if required.

The quality and value of scientific, clinical and medical education research is critically dependent on the integrity and rigor of with which is conducted. The National Institute of Health Research (NIHR) defines good clinical practice as “the international ethical, scientific and practical standard to which all clinical research is conducted, recorded and reported”. Thus, good clinical research practice extends beyond ethics to encompass honesty, accountability, professional fairness and good stewardship or governance. GCP sets out the responsibilities of those parties involved in research including investigators, sponsors, monitors and institutional review boards. The Research Governance Framework for Health and Social Care requires that everyone involved in the conduct of clinical research must be competent to perform their tasks, qualified by education, training and experience. In most surgical specialties, GCP training in Research Governance is now a Joint Committee Surgical Training (JCST) requirement for certification for completion of training (CCT).

The International Conference on Harmonization (ICH) has standardized GCP recommendations between Europe, the U.S. and Japan, which is particularly advantageous for international research collaborations and in industry. However, GCP has been criticized due to over emphasis on monitoring and reporting and the significant economic implications of ensuring compliance, which may not improve research quality. Before you undertake any form of clinical research, or contribute to clinical trials, you must undertake formal training in Good Clinical Practice. This is available online or through a half day face to face training session.

GCP requires that research data are recorded, handled, and stored in a way that allows accurate reporting, interpretation and verification while respecting the confidentiality of participants. Data protection legislation governs the use of data generated through research and stipulates when and how it can be collected, stored, used, transferred and disposed. The requirements and technical processes for data management, retention and preservation are determined by the type of study being conducted. New General Data Protection Regulations (GDPR) were introduced in May 2018.

One of the principles of GCP is transparency of conduct. Legitimate conflicts of interest (e.g. academic, clinical and personal) can occur during a project and should be identified, declared and addressed if necessary, to maintain transparency.

The emphasis and esteem placed on published research for career advancement predisposes to improprieties in the execution and reporting of research both in science in general and in academic or clinical surgery. The US office of Science and Technology Policy defines research misconduct as “fabrication, falsification, or plagiarism in proposing, performing or reviewing research”. Quantifying the forms and frequency of impropriety is, however, difficult. A meta-analysis of survey data of scientific misconduct found that 2% of scientists across all disciplines admitted to fabrication or modification of data at least once and up to 34% admitted to other questionable practices1. There is evidence that research fraud is increasing. As a proxy marker, the number of articles retracted has increased 19 fold from 2001 to 20102. A high-profile example of research fraud in a surgical setting is that of Paolo Macchiarini, a former thoracic surgeon and regenerative medicine researcher, who fabricated academic positions and qualifications. He also performed experimental surgeries using donor or synthetic trachea models enveloped in patient stem cells to minimize rejection. Although seven out of eight patients receiving such grafts died, misleading reports of treatment success were published, some of which have subsequently been retracted.

Not all misconduct is as dramatic. The Lancet retracted a trial on stem cell research on urinary incontinence because those involved failed to get valid ethical approval and, during the consent process, patients were not informed as to the experimental nature of the procedure. Furthermore, the head of the relevant Urology department denied involvement, despite having signed...