Clinical practice guidelines addressing Chinese patent medicine interventions: A systematic survey of 113 guidelines and 993 recommendations

Abstract

Chinese patent medicines (CPM) are widely used in China and are increasingly used in Western countries.¹ CPMs have gained social acceptance for fixed prescription, precise dosage, ease of use, and storage. Numerous CPM clinical trials have been conducted, with approximately 14,000 systematic reviews published in journals. Over 600 guidelines were published in the past two decades.² However, the clinical and methodological status, usefulness, and recommendations of CPMs remain understudied. This systematic review aimed to summarizes the clinical and methodological characteristics of CPM-related guidelines, critically assessing their methodological quality and usefulness.

China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP, SinoMed, MEDLINE, EMBASE, and Guidelines International Network, the scientific, transparent, and applicable ranking (STAR) tools for clinical practice guidelines³ and Practice Guideline Registration for Transparency (PREPARE) were searched. All of CPM-related guidelines published from January 2021 to December 2023 were included, no matter the type of guideline, which include CPM-specific guidelines (all recommendations solely focused on CPM interventions), TCM guidelines (encompassing recommendations on traditional Chinese herbal medicines, CPMs, acupuncture, and other TCM interventions), and integrated TCM and WM guidelines (offering recommendations on both conventional medicine and TCM interventions together).

A structured data extraction table was used to collect the data. Reviewers extracted three types of information from each guideline: (1) general information, including types of guidelines, target users, subjects, journal of the publication, sponsoring institutions, and diseases or conditions investigated; (2) CPM recommendation information, including the types of CPM recommended in the guidelines, strength and direction of the recommendation, and details of CPM interventions; and (3) usefulness information of CPM recommendations, for example, clinical questions, comparators, outcomes, and presentation of the recommendation. χ² was used to compare the variables across different types of guidelines when necessary and the significance level was set at 5% (p < 0.05).

A total of 113 guidelines with 933 recommendations for the use of CPMs were included. Only 4 (3.5%) guidelines were published in English and almost all guidelines (94.7%) focused on treatment. For the target users of the guidelines, more than half of the guidelines (56.6%) were formulated for TCM physicians and 46.5% for WM physicians. Only one guideline was enacted by primary physicians. 13.3% of the guidelines were investigator-initiated and the rest were sponsored by the China Association of TCM (31%), China Association of Traditional Medicine, China Association of Integrative Medicine and World Federation of Chinese Medicine Societies (38.9%). Non-TCM organizations of Chinese Medical Doctor Association and the Chinese Geriatrics Society sponsored 12.4% of the guidelines. Three types of CPM-related guidelines accounted for TCM guidelines (40.7%), integrated TCM and WM guidelines (28.3%), and CPM-specific guidelines (31%), respectively. Almost all CPM-specific guidelines (94.7%) focused on treatment. For the target users, more than half (56.6%) were formulated for TCM physicians, and 46.5% for WM physicians. Only one guideline was enacted by primary physicians.

The diseases or disorders of CPM-specific guidelines focused on chronic diseases (38.1%, including cardiovascular and cerebrovascular diseases, chronic inflammatory airway diseases, diabetes, and cancer), reproductive medicine (19.5%, including erectile dysfunction, premature ejaculation, varicocele, oligospermia, and asthenospermia in men and primary ovarian dysfunction and polycystic ovary syndrome in women), pediatrics (8.8%) and degenerative issues such as disk herniation, knee osteoarthritis, osteoporosis in orthopedics, age-related macular degeneration, dry eyes in ophthalmology, and Alzheimer's disease.

Seventy-nine (69.9%) used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess the certainty of evidence. Additionally, 11 (9.7%) used the Evidence Body of Traditional Medicine, an evidence-based grading tool proposed by Chinese researchers in 2007, to assess the characteristics and status of clinical research in TCM. The Oxford Center for Evidence-Based Medicine (OCEBM) system was used in five guidelines. Notably, 13 (11.5%) guidelines did not use any evidence-grading tool, and there was no certainty of evidence in the recommendation. Of all the 933 CPM recommendations, the strength of strong recommendation accounted for 122 (22.4%), weak recommendation was 590 (63.2%), and 221(23.7%) recommendations did not provide any direction or strength. 44.7% of the strong recommendations were supported by evidence of low or very low certainty. 30.9% considered treatment benefits, certainty of evidence, cost, adverse events, and feasibility as important issues when making recommendations. Only a few guidelines have been published on patient values and preferences.

The CPM recommendations and remarks provided limited details regarding CPM interventions. Oral preparations (88.3%) were the most frequently recommended treatment, and 95(10.2%) were injections. External preparation and novel forms such as aerosol of CPM were recommended in only 3.8% of the cases. More than 83.6% of the recommendations in the TCM and WM guidelines did not report the type of CPM therapy (alone or combined with other interventions). Most recommendations in the CPM guidelines emphasized combination or adjunct therapy, with less than 30% recommending stand-alone CPM use. The recommendations in TCM and WM guidelines were most frequently based on syndrome differentiation in TCM, while CPM-specific guidelines often focused on symptoms. Only 8.9% of CPM recommendations were based on the treatment habits of modern medicine. Furthermore, 13.7% of CPM recommendations did not describe any indications for CPM use or specify which patients could benefit from them.

For the usefulness of the recommendation, while all CPM-specific guidelines were based on specific questions, only 12.8% were derived from TCM and TCM and WM guidelines. Of the guidelines evaluated, 81.4% had clear references, but only 43.4% were based on systematic reviews. In CPM-specific guidelines, recommendations were often presented in figures and tables or signed with overstriking, underlining, or other forms, while recommendations in TCM guidelines and TCM and WM guidelines were typically articulated in words. Although 76.1% of guidelines provided sufficient details regarding CPM dosage and frequency, nearly none of the TCM guidelines, and TCM and WM guidelines specified the course of treatment. in order to clear and definite the target patients of each CPM, CPM guidelines tended to focus on specific symptoms or characteristics of conventional medicine, while TCM and WM guidelines relied on syndrome differentiation. CPM-specific guidelines were superior to TCM and TCM and WM guidelines in explicitly describing comparators and providing evidence on “patient-important” outcomes. However, all included guidelines lacked consideration of patient values and preferences.

The authors declare no conflict of interest.

This study was supported by funded by the National Administration of Traditional Chinese Medicine China (SATCM-2015-BZ402, GZY-FJS-2022-040) and the National Health Commission of China (JKZGJBGG2331).