I am often challenged by polite, well-intentioned, but misinformed individuals about medical matters, that the treatments doctors prescribe are without basis in fact. Thus inspired, I want to explain how doctors acquire data through medical research, so strap on your chute and buckle up!
Just as ice cream comes in many flavors, so does research: reviewing clinical experience over the years; combining ten small studies into one big study (meta-analysis); clinical trials in carefully selected patient groups with a given disease, comparing Treatment A to Treatment B. Or basic benchtop science with cultured cells exploring the intricacies of mitochondria or genes. Or animal experiments with non-human species.
Why do doctors conduct research? Primarily, to satisfy curiosity; just as people climb mountains or challenge their flying skills. Seeing one’s labors changing medical practice, possibly saving or improving lives, is a thrill. Obtaining academic tenure and invitations to lecture at conferences or teach in far-flung locales are all wonderful, but expanding medical knowledge is the key driver.
If animal experimentation is required, application for permission is made to an Institutional Animal Care and Use Committee (IACUC), which serves to ensure animal use is humane, relevant, and meaningful. It is never done without much soul-searching.
For any research project, one first defines a hypothesis, the question one seeks to answer. Statisticians and other experts help write a protocol, an instruction manual on how the research will proceed, and it will likely require multiple iterations. One must endeavor to ensure a trial will yield meaningful results and be applicable to a broad population. How should a trial be constructed? Which participants to study (in trials, these are participants or subjects, not “patients”)? What risks are faced, and how might they be mitigated?
For human clinical trials, promotional materials are required to attract patients to participate, as well as a specific patient consent form to explain everything in layman’s terms. All documents are submitted to an Institutional Review Board (IRB) or Ethics Committee, who govern whether research is permissible. Initially emanating from the Nuremberg trials, specifically The Doctors’ Trial (USA v. Karl Brandt, et al) after the Nazi human experimentation horrors during World War 2, this has been amended, taking medical advances into consideration. Recruitment, and the intention to publish data, demands trials be registered at public-facing websites like www.clinicaltrials.gov, ensuring all can see what is available.
Research is expensive – one must fund:
Conducting a trial “always takes longer than it takes.” An old aphorism states that if one wants to cure a disease, start a clinical trial and patients disappear! With data gathered, numbers are crunched and statistically analyzed, ensuring one avoids the traps Darrel Huff so eloquently outlined in his classic book, How to Lie With Statistics (W.W. Norton & Company, New York, 195, ISBN 0 -393-31072-8). Then, a scientific paper is written disclosing all these steps; authors declare their conflicts of interest and define their contributions. The order in which authors appear follows a convention. The last author is the most senior team member; the first, or “lead” author, is often junior and did all the hard work; and the remainder, based on elements they brought to the table.
An abstract, or brief précis, of the paper may be submitted to a medical conference for consideration of presentation as a lecture or a poster, a display board characterizing the work. It will also be sent to an appropriate and renowned journal, based on their research and audience coverage and impact factor, a measure of how their publication is viewed professionally. Just as for conferences, papers are peer-reviewed, whereby two, three, or more subject-matter experts read and comment on the paper, either accepting or rejecting it outright or asking for modifications; the most prestigious journals have acceptance rates below 10%!
Once published, study design, results, statistics, conclusion, discussion and any recommendations may be discussed in the correspondence pages or be the subject of an editorial by journal editors or invited commentators. Some journals nowadays are “open access,” accelerating speed to publication and large audience, some are supported by advertising, and others by scientists paying for publication of their article.
Medical journals are expensive and healthcare practitioners rely on hospital libraries or online databases to access articles. On occasion, readers contact authors requesting reprints of the article, printed or delivered electronically. The author pays, but it is considered a privilege to send these to one’s colleagues.
Research and publication are designed with checks and balances as alluded to above; however, wrongdoing does occur. Grants are obtained under false pretenses, data fabricated or falsified, and shortcuts taken. In addition, plagiarism occurs, not just copying the work of others, but publishing the same data in multiple journals, a practice made harder by various systems including artificial intelligence. Each time this occurs, loopholes are detected, wrongdoers are shamed and punished, and the system improves. However, examples of such behaviors make for interesting reading; whether Bharat Aggarwal’s fraudulent assertion that curcumin could prevent cancer, Elias Alsabti’s plagiarized cancer publications with non-existent co-authors, Joachim Boldt’s forged publications, or the posthumous discovery that statistics in Cyril Burt’s work on IQ were faked and his co-authors were, like Alsabti’s, figments of his imagination! These outrageous deceits undermine faith in science, but for every one of these egregious actions there are tens of thousands of hard-working men and women with curious minds and unflinching moral compasses.
In my professional lifetime, medicine has changed dramatically, and the rate of change is accelerating. For instance, research ascertained that cervical cancer was caused by a virus, leading to a test to identify it and then a vaccine to prevent it. Similarly, Drs. Barry J. Marshall and Robin Warren won the Nobel Prize in medicine for proving that peptic ulcers are caused by a bacterium, Helicobacter pylori, and the operations I learned to do as a trainee were condemned to the history books as drug treatment replaced them.
So, this rather expanded epistle is in answer to the chap who suggested that, rather like a well-known brand of athletic shoes, doctors “just do it.” I hope this shows that no, we don’t.
And parachutes? Well, the “gold standard” for clinical research is the prospective, double-blind, randomized, placebo controlled clinical trial. This is where one studies interventions in advance, allocating subjects to one or more “treatments” and another, deemed to be non-therapeutic. Many of us feel that while this form of trial has its place, in some cases it is, quite literally, overkill. In a tongue-in-cheek 2003 article in the British Medical Journal (BMJ 2003;327:1459-1461 (20 December doi:10.1136/bmj.327.7429.1459), “Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomized controlled trials,” Gordon Smith and Jill Pell suggested that because there was no published randomized controlled trial confirming, without doubt, that jumping out of a plane with a parachute was better at preventing injury than exiting without one, “that everyone might benefit if the most radical protagonists of evidence based medicine organized and participated in a double blind, randomized, placebo controlled, crossover trial of the parachute.” Perhaps a tad extreme, but you get the picture! Fly well!
I am really excited to announce a new podcast I am doing with my old medical school colleague and dear friend, Dr. Nigel Guest, which went “live” on March 12, 2024. You can subscribe free at www.jointhedocs.com, on YouTube: @JoinTheDocs,
Instagram:@JoinTheDocs, TikTok: @JoinTheDocs, Facebook: @JoinTheDocs,Twitter: @JoinTheDocs
....and on Spotify or Apple or wherever you get your podcasts @jointhe docs. I hope you enjoy!
You can send your questions and comments to Dr. Sackier via email: [email protected]
