Every medical student learns about the risk-benefit ratio in medical research and in treatment. "For research that involves more than minimal risk of harm to the subjects, the investigator must assure that the amount of benefit clearly outweighs the amount of risk. Only if there is a favorable risk–benefit ratio may a study be considered ethical. The Declaration of Helsinki, adopted by the World Medical Association, states that biomedical research cannot be done legitimately unless the importance of the objective is in proportion to the risk to the subject. The Helsinki Declaration and the CONSORT Statement stress a favorable risk–benefit ratio." [1] For a rosacean, it would be prudent to understand what the risk-benefit data is for any rosacea treatment being considered. If you are seeking medical treatment from a physician, legally this must be provided to the patient clearly in terms that the patient can understand. What are the risks involved and what are the benefits for a particular rosacea treatment? Clearly the benefits should outweigh the risks, however, because the Benefit-risk assessment (BRA) mainly relies on a qualitative assessment of quantitative data, there is sometimes subjective or qualitative bias involved in the decision. Also the placebo/nocebo effect may be involved as well which is a factor in the outcome of the treatment. [2]     Bias For an example, take the common bias in the perception of risk in flying vs. driving. Some feel that flying is more risky than driving, however, statistics show otherwise. The bias in this case is subjective or qualitative on the quantitive data. "In the end in any given situation, the acceptable risk-to-benefit balance is an individual judgement on the part of the patient or the prescriber." [3] Due to this bias, clinical research studies use 'double-blinded' techniques. "In a blind or blinded experiment, information which may influence the participants of the experiment is withheld (masked or blinded) until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expectations, observer's effect on the participants, observer bias, confirmation bias, and other sources." [4] Placebo/Nocebo Effect "Evidence for the relevance of placebo and nocebo effects in dermatology is also increasing...A large proportion of the success or failure of dermatological treatment can be explained by factors other than the treatment mechanisms themselves. Placebo and nocebo effects, in particular, strongly contribute to treatment outcomes, with explained variances comparable to, for example, effects of analgesics or antidepressants....the placebo responses and positive expectations of patients will only endure if they are based on trust in a long‐term authentic relationship. Highly optimistic promises followed by limited effects will probably result in nocebo instead of placebo effects."  The placebo/noebo effect is a significant factor in whether a rosacean decides to accept a treatment or reject it as well as a huge factor in the outcome of the treatment. [5] Criteria for Assessing Risk-Benefit "The concept of risk is generally understood to refer to the combination of the probability and magnitude of some future harm. According to this understanding, risks are considered "high" or "low" depending on whether they are more (or less) likely to occur, and whether the harm is more (or less) serious." Benefit-risk Assessment Of course, there are a number of rosaceans who give absolutely no consideration to the risk-benefits of any given rosacea treatment (rely totally on what a physician proposes without hesitation, inquiry or investigation into this subject), while others investigate these risks-benefits in methodical and incredible details. For example, what is involved in investigating PDL for rosacea? Informed consent is the right of each patient and the responsibility of the medical practitioner. However, in over the counter or non prescription treatments for rosacea the responsibility of gathering the risk-benefit data relies totally on the rosacean, who relies heavily on anecdotal reports and very little scientific data, if any, probably in both cases provided by the promoter of the rosacea treatment under consideration. Independent verified anecdotal reports are highly valued, but as many have discovered, anecdotal reports can be faked. What can help in making a merit decision in any proposed rosacea treatment? A principle to consider is, 'a treatment causes benefit in many at the cost of serious injury in some.' Obviously if this principle is reversed, 'a treatment causes serious injury in many at the cost of benefit in some' would you accept the treatment? That would depend on how bad your rosacea is, now wouldn't it? The dilemma in this decision is understanding whether the data that is presented is valid or biased. That is what research and development is all about and why the RRDi was formed and a principle found in our mission statement.  End Notes  [1] Risk-benefit ratio, Wikipedia [2] Dialogues Clin Neurosci. 2011 Jun; 13(2): 183–190. Assessing the benefit:risk ratio of a drug - randomized and naturalistic evidence François Curtin, MD and Pierre Schulz, MD [3] Drug Saf. 1996 Jul;15(1):1-7. Concepts in risk-benefit assessment. A simple merit analysis of a medicine? Edwards R, Wiholm BE, Martinez C. [4] Blinded Experiment, Wikipedia [5] Placebo/Nocebo Effect in Rosacea  

Artemisia Image Courtesy of Wikimedia Commons "Artemisinin (ART), an anti-malaria drug, was reported to have several effects including anti-inflammation and anti-angiogenesis activities. However, the role of ART on rosacea remains unclear....ART ameliorated rosacea-like dermatitis by regulating immune response and angiogenesis, indicating that it could represent an effective therapeutic option for patients with rosacea." Biomedicine & Pharmacotherapy Volume 117, September 2019, 109181 Artemisinin, a potential option to inhibit inflammation and angiogenesis in rosacea Xin Yuan, Ji Li, Yangfan Li, Zhili Deng, Lei Zhou, Juan Long,Yan Tang, Zhihong Zuo, Yiya Zhang, Hongfu Xie Artemesinin is in the list of anti-malaria treatments used for successful rosacea treatment. Technically, artemisinin is not an anti-viral, but an anti-malaria treatment used on Plasmodium falciparum, a protozoa. Hopefully, we will hear of anecdotal reports of Rosaceans using artemisinin for rosacea with positive results. "Artemisinin derivatives are known for their ability to suppress immune reactions such as inflammation." Wikipedia Artemisinin is available over the counter and considered one of the Anti-parasitic Prescription Agents.

More has been uncovered in a report published in Cell Reports, April 7, 2020 by Balka et al. who report, "We further demonstrate that TBK1 acts redundantly with IkB kinase ε (IKKε) to drive NF- kB upon STING activation."  While this may be daunting to understand for a layman, James Ives, News Medical Net, explains the significance of this, "The two signalling arms of the cGAS-STING pathway were thought to be mediated by a single upstream kinase, TANK binding kinase (TBK1)...."That basically told us that the mechanism that drives the second cytokine pathway depends on both proteins, but that they act redundantly - if one's missing the other one does the job,"..."  Read the clinical paper below:  PIIS2211124720303703.pdf

It is with sad hearts that Steve Johnson, D.O., who has served for many years on the RRDi board of directors has resigned due to his busy work at his clinic. Steve will be missed. 

Related Articles Efficacy of Topical Ivermectin for the Treatment of Cutaneous and Ocular Rosacea. Ocul Immunol Inflamm. 2020 Apr 07;:1-5 Authors: Sobolewska B, Doycheva D, Deuter CM, Schaller M, Zierhut M Abstract Purpose: To investigate the efficacy of once-daily topical treatment of ocular and cutaneous rosacea with ivermectin 1% cream (Soolantra®, Galderma).Methods: Ten patients with rosacea were evaluated in a retrospective monocentric pilot study. Subjective symptoms (measured with the Ocular Surface Disease Index), skin findings, and ocular changes (blepharitis with telangiectasia and meibomian gland dysfunction, conjunctival redness, tear breakup time (TBUT), and fluorescein staining of the cornea) were evaluated. The follow-up was 8 months (range: 5-12 months).Results: The OSDI score decreased in the 8th week of treatment (38.5 ± 21.7, P = .004). After 16 weeks, blepharitis (P = .004), and conjunctival redness (P = .008) had strongly improved, and grade 1 was seen in all patients until the end of follow-up. Fluorescein staining of the cornea (P = .001) and TBUT (P = .016) showed significant improvement until the last follow-up visit. No side effects were observed. Conclusion: Topical ivermectin cream 1% given daily is an effective and safe therapy against rosacea. PMID: 32255398 [PubMed - as supplied by publisher] {url} = URL to article