Una pungente verità – Parte 2/2

PTS Integrity Group
Gruppo integrità nella ricerca e frodi scientifiche Patto Trasversale della Scienza

Enrico Bucci – Temple University
Raffaele Calogero – Università di Torino
Piero Carninci – RIKEN Center
Pellegrino Conte – Università di Palermo
Andrea Grignolio – Università Vita e Salute San Raffaele
Luigi Marchionni – J.Hopkins University
Angelo Parini – INSERM, Toulouse
Gianluca Sbardella – Università di Salerno

Introduzione.

A seguito delle dichiarazioni del dott. Filippo Bosco circa l’utilizzo dell’agopuntura e dell’omeopatia in sala operatoria, sono state analizzate le 53 pubblicazioni varie da egli fornite in supporto, trovandole insufficienti o non pertinenti.

In questo articolo, proveremo ad investigare se tuttavia l’uso dell’agopuntura in ambito chirurgico o più generalmente clinico abbia qualche supporto, investigando la letteratura in maniera più approfondita ed andando quindi oltre il materiale fornito dal dott. Bosco.

D’altra parte, la divulgazione di quali siano i dati in letteratura appare quanto mai urgente, viste le sempre più frequenti notizie di integrazione in ospedali pubblici di pratiche complementari ed alternative scarsamente supportate, come per esempio avvenuto anche a Bologna, e non solo a Pisa – ove opera il dott. Bosco – ma anche a Torino (Azienda Ospedaliera O.I.R.M. S.Anna, ambulatorio di agopuntura in ginecologia), a Milano (Ospedale Luigi Sacco, II Divisione di malattie infettive), a Roma (Ospedale S.Andrea, Ambulatorio di Agopuntura), a Firenze (ASL 10, Centro Fior di Prugna), a L’Aquila (Servizio di Agopuntura c/o Unità Ospedaliera di Dermatologia – Centro Allergologico AUSL 04) e a Napoli (Ospedale S. Paolo a Cremano) e in chissà quante altre strutture (qui la fonte per queste notizie).

Analisi: materiale esaminato.

Per la nostra analisi, vorremmo considerare tutta la massa di evidenza clinica disponibile fino al 2019; allo scopo, dunque, considereremo le meta-analisi e le review sistematiche (quei lavori che cioè analizzano tutte le fonti primarie, ovvero gli studi clinici pubblicati fino a quel momento) e le meta-reviews (quei lavori cioè che analizzano le fonti secondarie, ovvero le meta-analisi di cui al punto precedente, valutandole nel loro complesso) pubblicate nel 2019.

Una ricerca su Pubmed restituisce i 29 lavori elencati di seguito che soddisfano ai criteri di rappresentare meta-analisi, reviews sistematiche o meta-reviews.

1. Armour M, Smith CA, Wang L-Q, et al. Acupuncture for Depression: A Systematic Review and Meta-Analysis. J Clin Med. 2019;8(8):1140. doi:10.3390/jcm8081140
2. Chen Y-Y, Li J, Chen M, Yue L, She T-W, Zheng H. Acupuncture versus propranolol in migraine prophylaxis: an indirect treatment comparison meta-analysis. J Neurol. 2020;267(1):14-25. doi:10.1007/s00415-019-09510-x
3. Fei Y, Fei R, Zhang J, Sun Y, Yu Q. Systematic Evaluation of Efficacy and Safety of Acupuncture Treatment for Patients with Atrial Fibrillation. Open Access Maced J Med Sci. 2019;7(3):461-466. doi:10.3889/oamjms.2019.036
4. Fu Q, Zhang L, Liu Y, et al. Effectiveness of Acupuncturing at the Sphenopalatine Ganglion Acupoint Alone for Treatment of Allergic Rhinitis: A Systematic Review and Meta-Analysis. Evidence-Based Complement Altern Med. 2019;2019:1-10. doi:10.1155/2019/6478102
5. He W, Li M, Zuo L, et al. Acupuncture for treatment of insomnia: An overview of systematic reviews. Complement Ther Med. 2019;42:407-416. doi:10.1016/j.ctim.2018.12.020
6. Hou W, Pei L, Song Y, et al. Acupuncture therapy for breast cancer‐related lymphedema: A systematic review and meta‐analysis. J Obstet Gynaecol Res. 2019;45(12):2307-2317. doi:10.1111/jog.14122
7. Jiang C, Jiang L, Qin Q. Conventional Treatments plus Acupuncture for Asthma in Adults and Adolescent: A Systematic Review and Meta-Analysis. Evidence-Based Complement Altern Med. 2019;2019:1-10. doi:10.1155/2019/9580670
8. Kim H, Kim HK, Kim SY, Kim Y Il, Yoo HR, Jung IC. Cognitive improvement effects of electro-acupuncture for the treatment of MCI compared with Western medications: A systematic review and Meta-analysis 11 Medical and Health Sciences 1103 Clinical Sciences. BMC Complement Altern Med. 2019;19(1). doi:10.1186/s12906-018-2407-2
9. Kim J, Kim S-R, Lee H, Nam D-H. Comparing Verum and Sham Acupuncture in Fibromyalgia Syndrome: A Systematic Review and Meta-Analysis. Evidence-Based Complement Altern Med. 2019;2019:1-13. doi:10.1155/2019/8757685
10. Kim S-H, Jeong J-H, Lim J-H, Kim B-K. Acupuncture using pattern-identification for the treatment of insomnia disorder: a systematic review and meta-analysis of randomized controlled trials. Integr Med Res. 2019;8(3):216-226. doi:10.1016/j.imr.2019.08.002
11. Lee I-S, Cheon S, Park J-Y. Central and Peripheral Mechanism of Acupuncture Analgesia on Visceral Pain: A Systematic Review. Evidence-Based Complement Altern Med. 2019;2019:1-22. doi:10.1155/2019/1304152
12. Li J, Li Y-X, Luo L-J, et al. The effectiveness and safety of acupuncture for knee osteoarthritis. Medicine (Baltimore). 2019;98(28):e16301. doi:10.1097/MD.0000000000016301
13. Li M, Xing X, Yao L, et al. Acupuncture for treatment of anxiety, an overview of systematic reviews. Complement Ther Med. 2019;43:247-252. doi:10.1016/j.ctim.2019.02.013
14. Liu F, You J, Li Q, et al. Acupuncture for Chronic Pain-Related Insomnia: A Systematic Review and Meta-Analysis. Evidence-Based Complement Altern Med. 2019;2019:1-10. doi:10.1155/2019/5381028
15. Liu Y, Meng H, Khurwolah MR, et al. Acupuncture therapy for the treatment of stable angina pectoris: An updated meta-analysis of randomized controlled trials. Complement Ther Clin Pract. 2019;34:247-253. doi:10.1016/j.ctcp.2018.12.012
16. Nishishinya Aquino MB, Pereda CA, Muñoz-Ortego J. Eficacia de la acupuntura en las enfermedades reumáticas que afectan el raquis: revisión sistemática. Med Clin (Barc). 2019;153(6):250-255. doi:10.1016/j.medcli.2019.04.020
17. Paley CA, Johnson MI. Acupuncture for the Relief of Chronic Pain: A Synthesis of Systematic Reviews. Medicina (B Aires). 2019;56(1):6. doi:10.3390/medicina56010006
18. Pouy S, Etebarian A, Azizi-Qadikolaee A, Saeidi S. The effect of acupuncture on postoperative pain, nausea and vomiting after pediatric tonsillectomy: a systematic review. Int J Adolesc Med Health. April 2019. doi:10.1515/ijamh-2018-0285
19. Smith CA, Armour M, Shewamene Z, Tan HY, Norman RJ, Johnson NP. Acupuncture performed around the time of embryo transfer: a systematic review and meta-analysis. Reprod Biomed Online. 2019;38(3):364-379. doi:10.1016/j.rbmo.2018.12.038
20. Tian Z-Y, Liao X, Gao Y, et al. An Overview of Systematic Reviews and Meta-Analyses on Acupuncture for Post-Acute Stroke Dysphagia. Geriatrics. 2019;4(4):68. doi:10.3390/geriatrics4040068
21. Trinh K V., Diep D, Chen KJQ. Systematic Review of Episodic Migraine Prophylaxis: Efficacy of Conventional Treatments Used in Comparisons with Acupuncture. Med Acupunct. 2019;31(2):85-97. doi:10.1089/acu.2019.1337
22. Vier C, Almeida MB de, Neves ML, Santos ARS dos, Bracht MA. The effectiveness of dry needling for patients with orofacial pain associated with temporomandibular dysfunction: a systematic review and meta-analysis. Brazilian J Phys Ther. 2019;23(1):3-11. doi:10.1016/j.bjpt.2018.08.008
23. von Trott P, Oei SL, Ramsenthaler C. Acupuncture for Breathlessness in Advanced Diseases: A Systematic Review and Meta-analysis. J Pain Symptom Manage. September 2019. doi:10.1016/j.jpainsymman.2019.09.007
24. Wei X, He L, Liu J, et al. Electroacupuncture for Reflex Sympathetic Dystrophy after Stroke: A Meta-Analysis. J Stroke Cerebrovasc Dis. 2019;28(5):1388-1399. doi:10.1016/j.jstrokecerebrovasdis.2019.02.010
25. Wu L, Chen X, Liu Y, et al. Role of acupuncture in the treatment of insulin resistance: A systematic review and meta-analysis. Complement Ther Clin Pract. 2019;37:11-22. doi:10.1016/j.ctcp.2019.08.002
26. Yu S, Zhu L, Xie P, et al. Effects of Acupuncture on Breast Cancer-Related lymphoedema: A Systematic Review and Meta-Analysis. EXPLORE. June 2019. doi:10.1016/j.explore.2019.06.002
27. Zhang N, Houle T, Hindiyeh N, Aurora SK. Systematic Review: Acupuncture vs Standard Pharmacological Therapy for Migraine Prevention. Headache J Head Face Pain. December 2019:head.13723. doi:10.1111/head.13723
28. Zheng H, Chen R, Zhao X, et al. Comparison between the Effects of Acupuncture Relative to Other Controls on Irritable Bowel Syndrome: A Meta-Analysis. Pain Res Manag. 2019;2019:1-13. doi:10.1155/2019/2871505
29. Zhi F-Y, Liu J, Ma X-P, et al. Manual Acupuncture for Optic Atrophy: A Systematic Review and Meta-Analysis. Evidence-Based Complement Altern Med. 2019;2019:1-12. doi:10.1155/2019/1735967

Fra i lavori reperiti, 6 rappresentano meta-review e 23 costituiscono invece review sistematiche o meta-analisi di studi clinici primari.

Le condizioni cliniche considerate sono ricapitolate nella seguente tabella (la colonna sulla destra rappresenta il numero di articoli dedicati al’applicazione dell’agopuntura in una data condizione clinica).

MIGRAINE	3
BREAST CANCER‐RELATED LYMPHEDEMA	2
INSOMNIA	2
OROFACIAL PAIN	1
KNEE OSTEOARTHRITIS	1
RHEUMATIC DISEASE WITH SPINAL INVOLVEMENT	1
ANXIETY	1
MILD COGNITIVE IMPAIRMENT	1
BREATHLESSNESS IN ADVANCED DISEASES (COPD AND CANCER)	1
POSTOPERATIVE PAIN, NAUSEA AND VOMITING AFTER PEDIATRIC TONSILLECTOMY	1
CHRONIC PAIN	1
ATRIAL FIBRILLATION	1
CHRONIC PAIN-RELATED INSOMNIA	1
ASTHMA	1
DEPRESSION	1
OPTIC ATROPHY	1
EMBRIO TRANSFER IMPROVEMENT	1
POST-ACUTE STROKE DYSPHAGIA	1
FIBROMYALGIA	1
REFLEX SYMPATHETIC DYSTROPHY AFTER STROKE	1
VISCERAL PAIN	1
STABLE ANGINA PECTORIS	1
ALLERGIC RHINITIS	1
IRRITABLE BOWEL SYNDROME	1
INSULIN RESISTANCE	1

E’ possibile notare come le condizioni cliniche in cui si sperimenta l’agopuntura siano piuttosto eterogenee, ad indicare come la sperimentazione proceda a tutto campo, alla ricerca di indicazioni e definizioni applicative precise.

Analisi: risultati generali riportati

Per ciascuno dei lavori considerati, sono riportate nella tabella di seguito parole degli autori che meglio riassumono le conclusioni di ciascuno studio esaminato (la colonna di sinistra corrisponde alla numerazione nella prima tabella di questo articolo).

1	A significant correlation between an increase in the number of acupuncture treatments delivered and reduction in the severity of depression (p = 0.015) was found
2	Compared to propranolol, acupuncture showed superiority in reducing migraine episodes and with less harmful adverse events in indirect comparison.
3	Acupuncture has a good therapeutic effect and safety profile
4	Acupuncturing the sphenopalatine ganglion acupoint alone has a potential role in alleviating nasal symptoms, improving quality of life for patients, and the effectiveness of acupuncture in the treatment of allergic rhinitis, suggesting it as a considerable therapy for allergic rhinitis
5	Most of the reviews included suggested that the acupuncture group was more effective than the control group in the treatment of insomnia
6	acupuncture therapy can alleviate the upper limb swelling and improve the subjective pain and discomfort in patients with BCRL, regardless of the control intervention used.
7	Conventional treatments plus acupuncture did show a clinically and statistically significant improvement in the symptom response rate and the IL-6 level when compared with conventional treatments alone.
8	Electroacupuncture was an effective treatment for MCI patients by improving cognitive function.
9	Verum acupuncture is more effective than sham acupuncture for pain relief, improving sleep quality, and reforming general status in FMS posttreatment
10	Acupuncture using pattern identification led to significantly improved total effectiveness rate compared to medication.
11	The results of this review demonstrated significant improvements in visceral pain following acupuncture treatments.
12	Acupuncture may have more total effective rate, short-term effective rate, and less adverse reactions in treating KOA than western medicine.
13	Most of the included reviews indicated that acupuncture group was more effective than control group in the treatment of anxiety
14	Acupuncture therapy is an effective and safe treatment for CPRI, and this treatment can be recommended for the management of patients with CPRI.
15	Acupuncture plus medicine, or acupuncture alone may improve anginal symptoms and ECG results in patients with SAP.
16	Acupuncture improved cervical pain and functionality both immediately and in the short term. It also proved effective in the treatment of acute and chronic low back pain as the first therapeutic line, compared with placebo, and as an adjunct to other conventional treatments.
17	The large quantity of RCTs on acupuncture for chronic pain contained within systematic reviews provide evidence that is conflicting and inconclusive, due in part to recurring methodological shortcomings of RCTs.
18	acupuncture as a complementary method can prevent and reduce the severity of complications surrounding tonsillectomy
19	Evidence suggests acupuncture may be effective when compared with no adjunctive treatment, with increased clinical pregnancies and live births, but is not an efficacious treatment when compared with sham controls.
20	High quality trials with large sample sizes should be the focus of future research.
21	These findings strengthened Linde et al.’s 2016 comparison of conventional treatments and acupuncture for reducing headache frequency at a 3-month follow-up. For episodic migraine prophylaxis, moderate evidence suggests that acupuncture is “at least non-inferior,” to now-proven, conventional treatments.
22	DN is better than other interventions for pain in the short-term. DN is better than sham therapy on pressure pain threshold in the short-term.
23	Acupuncture improved breathlessness severity in patients with advanced diseases.
24	Pooled data suggested that EA might be an effective therapy for RSD poststroke hemiplegia.
25	This systematic review suggests that acupuncture may be of therapeutic value in the treatment of insulin resistance by improving homa-IR, ISI, FBG, 2hPG and FINS, with fewer adverse events.
26	AC may be an effective method for improving the condition of breast cancer-related lymphoedema.
27	There is growing evidence that acupuncture is just as effective and has fewer side effects than many of the standard pharmaceutical agents that are currently used.
28	Relative to sham controls, acupuncture showed no superiority for treating IBS, while the advantage over western medicine was significant. Acupuncture could be used as an adjunct in clinical settings to improve efficacy. Future high-quality and large-sample-size studies with adequate quantity-effect design need to be conducted.
29	Despite statistical advantages of manual acupuncture in the literature, due to serious methodological flaws in study design, it cannot be concluded that manual acupuncture is more effective than medicine alone. It is essential that a properly controlled clinical trial is designed and controls are established to exclude placebo effects.

Per due studi, il 18 e il 21, non è stato possibile accedere al testo completo dell’articolo; per il resto, su 27 studi esaminati, cinque lavori riportano conclusioni negative circa la possibilità di misurare effetti clinici reali dell’agopuntura o l’assenza di effetti (in grassetto in tabella), mentre in 22 casi gli autori esprimono il loro favore all’agopuntura, che dalla letteratura risulterebbe avere qualche effetto come trattamento integrativo o come trattamento in sé. Si tratta tuttavia, come vedremo nella prossima sezione, di “wishful thinking” e di considerazioni puramente qualitative, non supportate da solida evidenza quantitativa.

Analisi: bias e qualità degli studi considerati

17 lavori, cioè circa il 60%, coinvolgono istituzioni di ricerca cinesi (15 di essi solo istituzioni cinesi); 5 lavori (3 in via esclusiva) coinvolgono istituzioni di ricerca coreane, per un totale di 21 studi che coinvolgono istituzioni basate in Cina o Corea (circa i 3 quarti del totale).

Il dato sulla provenienza non è irrilevante: è infatti noto da tempo che, proprio nel settore delle applicazioni dell’agopuntura, vi è un fortissimo pregiudizio positivo per quel che riguarda i lavori prodotti in certi paesi, primo fra tutti la Cina, ma anche, ad esempio, Corea e Taiwan. In proposito, si veda ad esempio:

Vickers A, Goyal N, Harland R, Rees R. Do certain countries produce only positive results? A systematic review of controlled trials. Control Clin Trials. 1998;19(2):159-166. doi:10.1016/S0197-2456(97)00150-5

Questo bias culturale non manca di essere sottolineato anche dagli autori cinesi di alcuni dei 29 studi recuperati; in proposito, per esempio, si legge nello studio numero 29 che:

the publication language of all the included studies was Chinese, suggesting a possibility of publication bias

problema evidenziato anche dagli autori cinesi dello studio numero 15:

our study did not include data from clinical trials written in other languages except mandarin Chinese

ed anche da un altro gruppo di ricercatori cinesi, che nel lavoro 28 scrivono:

Acupuncture seemed to be superior over western medicine, but the placebo effects couldn’t be ignored for all the studies were conducted in China

A questo punto, trascuriamo pure la provenienza degli articoli, che come abbiamo visto in maggioranza arrivano da paesi preconcettualmente favorevoli all’agopuntura.
In concreto, che indicazioni ci danno gli autori circa l’affidabilità dei dati che essi stessi hanno revisionato?

Per scoprirlo, bisogna andare al di là dell’abstract e delle frasi di conclusione, con cui i gruppi di ricerca spesso chiudono positivamente i propri lavori, e cercare le valutazioni tecniche fatte all’interno della discussione.

Di seguito, ecco le parole usate dagli autori per descrivere la qualità dei dati revisionati, per ciascuno dei lavori identificati.

1	The majority of the included trials were at a high risk of bias for performance blinding. The applicability of findings in Chinese populations to other populations is unclear, due to the use of a higher treatment frequency and number of treatments in China. The majority of trials did not report any post-trial follow-up and safety reporting was poor.
2	First, our evidence is indirect. Direct comparative studies are still needed to confirm our findings before generalizing the result to practice. Second, we included five RCTs about propranolol, but the doses vary from 60 to 180 mg/day, it may underestimate the effectiveness of propranolol. Third, acupuncture prescriptions are not consistent in these 12 trials which included acupuncture. Five trials used fixed acupoints for all patients; five trials used part standardization prescriptions; two trials described no acupoint prescription. Heterogeneity in acupuncture protocol may contribute to the statistical heterogeneity of the samples. Fourth, the common comparator between acupuncture and propranolol is flunarizine from only one trial, which may influence robustness of the study results.
3	Small, heterogeneous sample of studies; predatory publication
4	More studies are needed to execute a subgroup analysis of various variables and to evaluate the publication bias of the study
5	The methodological quality of most of the studies and the quality of evidence were low
6	the number of high‐quality RCT is low. Moreover, most of the studies adopted inconsistent efficacy indicators. Hence, additional blinded, large‐sample, randomized, well‐controlled studies with objective and uniform efficacy indicators are needed
7	Only two studies including 126 patients compared the effects of IL-6 between the two groups; the sample size was too small. Conventional treatments plus acupuncture did not show any beneficial effects on pulmonary function in asthmatic patients over conventional treatments alone.
8	The included studies presented a low methodological quality and no adverse effects were reported. Thus, further comprehensive studies with a design in depth are needed to derive significant results.
9	Evidence that it reduces fatigue was not found. Only 5 out of 8 studies were blinded. Evidence quality of moderate level in pain relief made our confidence in the effect estimate limited. On the other hand, we could not find any evidence that acupuncture has the ability to improve fatigue in FMS.
10	Results of overall risk of bias assessments were unclear or high. This study has limitations of high risk of bias, not using a standardized pattern-diagnosis-treatment and not comparing with standarized acupuncture without pattern identification.
11	Out of the seven studies, three studies were classified as having low overall risks of bias. Further, two randomized studies were considered as having high risks of bias due to concerns regarding possible selective reporting. Moreover, there were some concerns regarding three randomized studies with regard to randomization domains.  Lastly, there were some concerns regarding missing data associated with two studies because they did not provide clear indications on whether the results that were summarized in the texts or figures were from all the study participants. High heterogeneity among the included studies (various visceral pain conditions and models along with diverse outcome measures and heterogeneous results) and the lack of detailed descriptions outlining the treatment methods also raise concerns.
12	There might be missing information. There may be duplicated clinical trials included by each SR that might have impact on the synthetic findings. There are some risk of bias and reporting deficiencies still needed to be improved.
13	The methodological quality of the included reviews and the quality of evidence were low.
14	Due to the low quality and small sample size of the included studies, more rigorously designed RCTs with high quality and large sample size are recommended in future.
15	First, the quality of the included trials was inconsistent according to the Cochrane Handbook. In most of the included trials, the sample size was small, the randomization method was mentioned without further details, and double-blinding was not conducted. Second, our study did not include data from clinical trials written in other languages except mandarin Chinese. In addition, the classification of markedly effective, effective, ineffective and exacerbation did not conform to international standards.
16	acupuncture efficacy in radiculopathies (cervical, lumbar), lumbar spinal stenosis and ankylosing spondylitis is still inconclusive. Well-designed studies with medium and long-term evaluation are required. En general los estudios primarios analizan resultados de forma inmediata, a corto plazo y algunos estudios a 3 meses. No se dispone de resultados a largo plazo. Tampoco hay datos con respecto al consumo de antiinflamatorios o fármacos analgésicos. Con respecto a la acupuntura simulada, en algunos estudios no están descritos qué tipo de «simulación» se utilizó, ya que en algunos casos esta intervención «control» no es inerte, por lo que lleva a una subestimación del verdadero tamaño del efecto de la acupuntura verdadera per se.
17	The majority of SRs found that RCTs of acupuncture had methodological shortcomings, including inadequate statistical power with a high risk of bias. Heterogeneity between RCTs was such that meta-analysis was often inappropriate.
18	Not Accessible
19	A limitation of this review is the significant heterogeneity found across studies. Although a random-effects model was applied, these differences remained.
20	Currently, evidence on the effectiveness of acupuncture on post-acute stroke dysphagia is of a low quality.
21	Not Accessible
22	Due to the very low quality of evidence and the small effect size, caution is needed. Due the low quality of evidence and high risk of bias of some included studies, larger and low risk of bias trials are needed to assess the effects of dry needling on orofacial pain associated with temporomandibular joint dysfunction.
23	The high level of heterogeneity of the included studies and the limited amount of studies did not provide rigorous evidence to allow recommendations on the use of acupuncture in this field.
24	The statistical power was impaired by heterogeneity and bias, the evidence strength was reduced by small sample size and intervention confounding factor. To obtain robust and convincing evidence, rigorous, standardized, multicentric, high-quality, long follow-up, multidimensional outcome measures, and good-designed RCT is indispensable.
25	The conclusions are limited by flaws in the methodologies of the included RCTs. In the future, we look forward to further multi-centre and rigorous blinded studies for more solid evidence.
26	due to the high risk of bias and the low quality of the available studies, further high-quality RCTs are needed to confirm the efficacy of AC for breast cancer-related lymphoedema patients.
27	the heterogeneity of the existing studies limits the effective comparison and analysis. In the attempt to analyze and compare the data across trials, we encountered tremendous heterogeneity in the study protocols, acupuncture strategies, and outcome measures.
28	Taken together, for improvement of IBS symptoms and quality of life, no difference was found in acupuncture relative to sham controls studies, while some studies indicated positive results of acupuncture in alleviating IBS symptoms, reflective of a larger potential for treating IBS by true acupuncture. Acupuncture seemed to be superior over western medicine, but the placebo effects couldn’t be ignored for all the studies were conducted in China.
29	(1) only two studies clearly described the random method, while the rest only mentioned “randomization” without specific details, suggesting that there may be selective bias; (2) all the studies did not mention about blinding of participants or personnel, which may cause performance bias; (3) the publication language of all the included studies was Chinese, suggesting a possibility of publication bias; (4) none of the included studies reported follow-up and adverse reactions, suggesting that there may be other sources of bias.

Per due studi, il 18 e il 21, non è stato possibile accedere al testo completo; per tutti gli altri, si nota un florilegio di bias molto seri, primi fra tutti la limitata dimensione dei campioni negli studi inclusi, la loro eterogeneità, la cattiva definizione degli obiettivi primari e secondari, il mancato confronto con un vero placebo, la mancata o cattiva randomizzazione e molto spesso l’assenza di procedure in cieco.

Non una delle revisioni primarie o secondarie della letteratura clinica pubblicata nel 2019 è scevra da almeno alcuni fra i bias elencati.

D’altronde, possiamo verificare immediatamente alcune fra le pesanti limitazioni identificate dagli stessi autori: la dimensione media degli studi clinici inclusi nel campione considerato, per esempio, è di 99 individui (includenti sia il gruppo trattato che quello di controllo).

Le procedure considerate includono sia l’agopuntura “tradizionale” che l’elettroagopuntura, e i protocolli di trattamenti sono estremamente eterogenei circa tempi e durata dell’applicazione dell’agopuntura, sede di applicazione del trattamento, numero di trattamenti e misura dell’effetto del trattamento.

Molto spesso, l’agopuntura è somministrata in aggiunta ai normali trattamenti, e l’effetto misurato consiste in una diminuzione di effetti negativi o di dose farmacologica dei farmaci somministrati in aggiunta; ma non vi è il controllo costituito da un gruppo cui, senza l’agopuntura, si diminuisca la dose dei farmaci, per verificare se, semplicemente, la dose usualmente utilizzata possa essere leggermente diminuita, senza grosse complicazioni.

I controlli (quando ci sono) sono spessissimo inappropriati, consistendo a volte nell’applicazione di aghi a caso (ed in questo caso, si rileva persino talvolta che l’applicazione degli aghi a caso ha lo stesso effetto dell’applicazione eseguita seguendo i dettami pseudoscientifici dell’agopuntura tradizionale) ed altre volte in un trattamento farmacologico tradizionale, rendendo quindi impossibile la procedura in cieco.

Sulla base di queste osservazioni, la gran maggioranza degli autori, pur favorevole all’agopuntura, non può che concludere che, anche in presenza di apparenti benefici clinici dell’agopuntura (deformati dalla scarsa qualità degli studi), sono necessari studi più ampi, meglio disegnati e meglio controllati, prima di poter verificare se e come l’agopuntura dia un qualche beneficio; il che equivale allo stato ad ammettere che non vi è nessuna indicazione solida circa tali effetti clinici.

Conclusioni.

In generale, la revisione della letteratura disponibile, che copre diverse centinaia di studi clinici primari, conferma la bassa qualità di tali studi e le severe limitazioni che ne affliggono l’interpretazione. Questo risultato è condiviso dagli stessi autori dei 29 articoli esaminati, ed è ulteriormente verificabile andando a studiare i dati richiamati (come in piccola parte si è tentato di fare qui).

L’eventuale trasferimento in clinica dell’agopuntura non appare quindi supportato sufficientemente dall’evidenza scientifica, neppure a voler prendere per buone le conclusioni ottimistiche degli autori favorevoli all’agopuntura, i quali tutti uniformemente indicano la necessità di studi clinici di maggiori dimensioni e con minori bias, necessari per verificare se vi sia alcun effetto oltre al placebo.

Appare dunque prematuro l’arruolamento di pazienti in strutture pubbliche, prima che tali studi siano effettuati.

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Post Scriptum

Durante la preparazione di questo articolo, la rivista Jama ha pubblicato una nuova meta-analisi per controllare gli effetti dell’applicazione dell’agopuntura al dolore oncologico, con conclusioni piuttosto positive per l’agopuntura.
Tuttavia, a quanto pare anche la qualità di questa meta-analisi è discutibile. I primi problemi sono già stati esposti dal prof. Edzard Ernst, e sono brevemente elencati di seguito:

• Circa metà degli studi clinici primari sono cinesi; già abbiamo discusso i bias legati alla provenienza dalla Cina di studi sull’agopuntura
• Molti degli studi inclusi sono pubblicati in cinese; questo rende difficile o impossibile la verifica della loro qualità (presumibilmente anche ai referees di Jama)
• Alcuni dei giornali che hanno pubblicato gli studi primari esaminati sono predatori o di bassa qualità
• Uno degli studi inclusi nell’analisi è una semplice tesi di dottorato, senza peer review
• Gli autori dichiarano di aver incluso solo trials che comparano l’agopuntura e l’acupresisone con controlli sham, terapia analgesica o trattamenti standard. Questo è falso; molti degli studi infatti hanno il classico disegno trattamento A+B contro B, paragonando un trattamento che comprende la normale procedura e l’agopuntura contro la procedura normale da sola. Questo disegno evidentemente non può produrre risultati negativi, anche quando “A” sia un placebo.
• Al contrario di ciò che gli autori proclamano, la qualità degli studi inclusi è spesso molto bassa (in termini di bias, disegno sperimentale e ampiezza del campione studiato)
• Uno degli studi incluso si intitola ‘Clinical observation on 30 cases of moderate and severe cancer pain of bone metastasis treated by auricular acupressure‘. Questo sarebbe un clinical trial randomizzato, secondo gli autori.