The determinants and effects of polypharmacy apply to COVID-19 as well as chronic conditions in older adults. Figure 1 is a directed acyclic graph (DAG) created by the present author to show the relationship of the findings in the present paper. The DAG shows that medication clinical trial reporting bias and unreported ARRs are upstream determinants leading to the downstream effects of biased medication benefits, poor clinical decision making, PIMs, and patient adverse effects from polypharmacy. Obviously, patients, clinicians, public health administrators and policy makers, pharmacists, pharmaceutical companies, researchers, educators, regulators, consumers, and other people involved with prescription medications are all eventually affected by upstream outcome reporting bias in medication RCTs.

A recent qualitative study that interviewed pharmacists and general practitioners explored the determinants of polypharmacy, but none of the interviewed participants appeared to challenge the reliability of the reported clinical trial outcomes of the medications that they prescribed and dispensed to patients [38]. An American national action plan to eliminate medication overload confirms that “health care providers do not have clear, accurate, up-to-date information on the harms and benefits of medications when making prescribing decisions”, and “clinicians and patients lack critical information and skills they need to appraise the evidence” [39]. The present paper provides critical information from analyses of unreported outcomes in medication clinical trials to help clinicians and patients reappraise evidence and improve medication decision making. Considering the pervasiveness of outcome reporting bias throughout the research literature, much more work lies ahead in establishing preventive measures to reduce outcome reporting bias in published RCTs [40].

The U.S. National Institute on Aging (NIA) notes that scientists are just beginning to explore the new field of deprescribing, and NIA has established a US Deprescribing Research Network to reduce polypharmacy harm in older adults [41]. Future deprescribing research should address outcome reporting bias in RCTs as a key (and often overlooked) upstream factor of polypharmacy. Additionally, “pharmaceutical companies are suspected of putting profits above public interest, using marketing techniques to distort scientific evidence, and actively influencing both physicians and health policy makers” [42].

An editorial in The Journal of the American Medical Association emphasized that patients “need to have trust in treatments recommended by clinicians during the time of COVID-19, including taking medications indefinitely for chronic conditions” [43]. The editorial described how patients must be reassured that their best personal needs are considered above the financial interests of others, but the editorial also pointed out that many factors have contributed to the public’s declining trust in the healthcare system over the past half century, which has been exacerbated by challenges of the COVID-19 pandemic. The editorial further pointed out that regaining the public’s trust requires “a broad, multifaceted approach, including expanding diversity within the scientific community, engaging communities in the design of clinical trials and the interpretation of results, and increasing the number of underrepresented minority groups in clinical trials.” Relevant to polypharmacy discussed in the present paper, public health campaigns are urgently needed to disseminate information and educate the public about medication outcome reporting bias as a determinant of the inappropriate use of medications in older adults.