Part 1 of this series on research methods covered the pros and cons of observational studies when it comes to e-cigarettes. As a quick recap, observational studies involve studying the behaviors of a target group and using these observations to make comparisons to a control group in an effort to draw a conclusion about a hypothesis.
When used to study e-cigs, an observational study might find survey results helpful in determining the links between two variables based solely on the behaviors of study participants, but such studies should not be used as concrete proof of a proposed theory or hypothesis.
Experimental research, on the other hand, usually involves more controlled circumstances and may provide more concrete evidence when forming a conclusion based on a suggested theory or hypothesis; however, this doesn’t mean experimental studies are flawless.
Experimental Research 101: The Study of E-Cigs
With experimental research, there are a few different types of studies used to determine the conclusion of a theory or hypothesis. For the purpose of this article, we will take a look at the two main types of experimental research used to study e-cigs: basic experimental research and clinical trials.
Basic Experimental Studies: In Vivo vs. In Vitro
There are two main types of basic experimental studies: in vivo studies, which involve testing on living organisms such as mice; and in vitro studies, which test the effects of a stimulus on cells or tissue in an artificial environment such as a test tube. Basic research studies are considered more effective than observational studies as they are performed in a very controlled environment. For this reason, basic experimental studies have been proven beneficial in many areas of scientific research; however, like observational studies, they do have their cons.
The Cons of Using Mice for E-Cig Research
Mice are popular in medical research because of the similarities of their biochemical pathways to humans, but the results of mice model studies do not always translate to human anatomy. Take, for example, the contradictory findings of two recent studies regarding the impact of e-liquid vapor on both mice and human lungs. A Johns Hopkins Bloomberg School of Public Health in vivo study found that exposing mice to e-cig vapor produced “mild effects on the lungs,” yet it concluded that e-cig vapor profoundly inhibited the mice’s ability to combat viral and bacterial infections.
The methods used in this study have undergone some serious questioning which has led to the conclusion that using mice to study electronic cigarettes may not be the most accurate route. For instance, upon reviewing this study in an evidence-based report, Public Health England (PHE) determined the study to be quite flawed due to the fact that the mice used in the experimental group suffered repeat nicotine poisoning and were exposed to a greater amount of stress than the control group. PHE claimed it was the methods used in this study that made the mice more susceptible to illness, rather than e-cig vapor, which resulted in the conclusion that “the mice model has little relevance for estimating human risk and it does not raise any new safety concerns.”
Related: E-Cigs – A Tale of Two Methodologies
In contrast to the in vivo study, a collaborative in vitro study conducted by British American Tobacco and MatTek Corporation found that e-vapor had a very different effect when tested on synthetically-grown human tissue. This study used synthetically grown human tissue identical to the tissue found in the human respiratory tract in combination with the use of a VITROCELL system, a robot that can mimic the act of inhaling, to determine the possible effects e-cig vapor may have on human airways.
Researchers found that six hours of inhaling cigarette smoke through the VITROCELL killed the synthetically grown tissue, but six hours of inhaling e-liquid vapor produced the same effects as inhaling air. As a result, the study concluded, “E-cigarette aerosols used in this study have no cytotoxic effect on human airway tissue.”
Clinical Trials and Electronic Cigarettes
Clinical trials are basic research studies that use human test subjects to explore whether a medical strategy, treatment, or device is safe and effective. This form of scientific research may actually provide the most accurate results out of any type of experimental study when it comes to determining the health benefits or risks associated with a new drug or other type of medical treatment. This is due to the fact that clinical trials study the direct effects between human test subjects and a controlled variable, rather than testing the effects on synthetically grown human tissue or animals with similar DNA composition.
There are many risks involved with this type of research, however, including unpleasant, serious or even life-threatening side effects that may result from the treatment. Since electronic cigarettes were not officially introduced to the market as a healthier alternative to tobacco, not many clinical trials have been conducted to determine the potential benefits and/or risks associated with the use of electronic cigarettes. However, that’s not to say there hasn’t been at least one clinical trial on electronic cigarettes, and contrary to the continued debate over whether e-cigs should be promoted as a smoking cessation device, this particular study produced some positive results for e-cigs.
Quitting Smoking via E-Cigs: The Double-Blind Experiment
Double-blind clinical trials are known for being one of the best methods for testing the effects of a drug or treatment while controlling for placebo effect and researcher bias. This method has provided some positive results in determining whether or not e-cigs should be used for smoking cessation.
For example, a study from the Institute of Psychiatry in London compared the effects that different levels of nicotine can have on e-cig users to determine if e-cigs containing nicotine can reduce the symptoms of tobacco withdrawal. A group of 40 smokers were given either an e-cig with nicotine or a nicotine-free e-cig and were asked to use the devices while abstaining from tobacco for 24 hours. Neither the participants nor the researchers knew which participants were given e-cigs containing nicotine and which were given the nicotine-free version, hence the term “double-blind.” Assignment of e-cig type was randomized to ensure diversity in both groups. Participants were then asked to periodically report how they were feeling throughout the day.
After 24 hours, the researchers took blood samples from the participants to confirm that they had indeed abstained from smoking. Once all of the data was collected, the researchers discovered that subjects who used e-cigs containing nicotine reported fewer withdrawal symptoms than those who had nicotine-free e-cigs. Therefore, the study suggests that e-cigs with nicotine are better at preventing tobacco withdrawal than those without nicotine. Such a study would also be easy to repeat on a larger scale, and doing so could confirm the results.
The Importance of Replicating Research
Unfortunately, many published experimental studies are not successfully replicated. For example, Dr. C. Glenn Begley, a former employee of the American drug company AMGen, told NPR that studies using lab mice have a high rate of faulty findings. In his review of 50 studies testing the effects of cancer drugs on lab mice, 90 percent of the study results failed to replicate in follow-up studies.
This shockingly high number is also cited in a Forbes article that offers some possible insight into the problem. According to medical researcher Dr. Henry I. Miller, when it comes to animal experimentation, “randomization and blinding are not a part of researchers’ culture, whereas the arbitrary dropping of animals from the results of a study is.” In other words, animal studies tend to have high rates of researcher bias.
Many researchers also leave out important information in their reports or include misinterpreted information and scientific errors, which means results are nearly impossible to replicate. For example, a now debunked study claiming that e-cig vapor contains formaldehyde involved heating e-liquid to such high temperatures that they produced thermal breakdown products, which is known to the vaping world as “dry puff” conditions. This essentially means the e-liquid was overheated to very high temperatures that were essentially determined to be “unvapeable” as the taste of overheated vapor is much too acrid for any vaper to handle.
Sensationalism and Experimental E-Cig Studies in the Media
While its main job is to deliver the latest news, the media often uses the results of experimental studies to create attention-grabbing headlines; and since electronic cigarettes are part of a still growing industry with so many uncertainties, the debate over their health and safety continues to dominate sensationalism in the media.
For instance, if you Google “the effects e-cigs have on the lungs,” you will not find the in vitro study mentioned earlier anywhere on the first page of search results. You will, however, find plenty of news articles like Vaping May Harm the Lungs.” It appears that once a scientific study of e-cigs with negative results is published, the media continues to create sensational headlines to grab their audience’s attention, while studies with positive results on e-cigs are pushed far below the slew of negative headlines.
It’s logical to assume that the media’s misinterpretation of scientific studies results from miscommunication and a lack of understanding between scientists and journalists, a recently published paper by two doctors from the University of North Carolina at Chapel Hill posits that the two fields could be working in tandem to create controversial headlines.
Take, for example, a Daily Beast article entitled “The Poison in Your E-Cigarettes” and its source material, the provocatively titled research report “A Smoking Gun: Cancer-Causing Agents in E-cigarettes.” The Center for Environmental Health claims their research is unbiased, but their report clearly seems more concerned with painting a narrative that demonizes e-cig marketing tactics rather than presenting scientific facts. Therefore, while researchers may not have nefarious intentions, they can be prone to the same sensationalism that is commonplace in news media.
Problems in Academic Publishing
A frightening trend in scientific research is predatory publishing. Whereas reputable academic journals are peer-reviewed, meaning an editorial team of scientists checks the quality of the papers it publishes, predatory publishers solicit academic studies promising instantaneous publishing, regardless of whether or not the information provided is accurate—that is, they don’t have any academic requirements for publication; they just want a hefty fee of $1,800 or so. As a result, the publishing credit looks great on paper until someone realizes that these journals have no oversight or standards. To add insult to injury, such predatory publishing often circulates through the media before being discredited, but by then it has already made a home for itself within sensationalist media.
The moral of the story here is: no one experimental study should be relied upon as a definitive source of information. The accuracy of an experimental study truly depends on whether or not the same study can be replicated multiple times with the same results each time. Now that we’ve learned a little bit more about scientific research, we’ll take a look at how the study of e-cigs compares to the FDA’s Prescription Drug Approval Process.
In Part 3 of this series, we take a look at the U.S. Food and Drug Administration’s process for prescription drug testing and approval to propose a path for where all of this e-cig research could eventually lead us. We also examine the government’s future role in vaping regulation and compare the proposed health benefits of e-cigs to the risks associated with legally prescribed drugs.