Colon Hydrotherapy an Update

HEALTH TECHNOLOGY ASSESSMENT SECTION MEDICAL DEVELOPMENT DIVISION MINISTRY OF HEALTH MALAYSIA 012/2009 i

DISCLAIMER Technology review is a brief report, prepared on an urgent basis, which draws on restricted reviews from analysis of pertinent literature, on expert opinion and / or regulatory status where appropriate. It is subjected to an external review process. While effort has been made to do so, this document may not fully reflect all scientific research available. Additionally, other relevant scientific findings may have been reported since completion of this review.

Please contact: [email protected], if you would like further information.

Health Technology Assessment Section (MaHTAS), Medical Development Division Ministry of Health Malaysia Level 4, Block E1, Precinct 1 Government Office Complex 62590 Putrajaya

Tel: 603 88831246

Fax: 603 8883 1230

Available at the following website: http://www.moh.gov.my

Prepared by: Dr Junainah Sabirin Principal Assistant Director Health Technology Assessment Section (MaHTAS) Ministry of Health Malaysia

En Sahaludin Sharif Assistant Medical Officer Health Technology Assessment Section (MaHTAS) Ministry of Health

Reviewed by: Datin Dr Rugayah Bakri Deputy Director Health Technology Assessment Section (MaHTAS) Ministry of Health Malaysia

External reviewer: Dr Wan Khamizar Wan Khazim Consultant Colorectal Surgeon Hospital Sultanah Bahiyah Alor Setar, Kedah

DISCLOSURE

The authors of this report have no competing interest in this subject and the preparation of this report is totally funded by the Ministry of Health, Malaysia

iii

EXECUTIVE SUMMARY

Introduction Colon cleansing (colon therapy) encompasses a number of alternative medical therapies intended to remove faecal waste and unidentified toxins from the colon and the intestinal tract. Colon cleansing may take the form of colon hydrotherapy (also called colonics or colonic irrigation) or oral cleansing regimens. Colon hydrotherapy uses enemas to inject water, sometimes mixed with herbs or other liquids, into the colon using special equipment. Oral cleansing uses dietary fibre, herbs, dietary supplements or laxatives. Practitioners believe colon cleansing removes accumulation of faeces from the walls of the large intestine which are believed to putrefy, harbour parasites or pathogenic gut flora to cause non specific symptoms and general ill-health (referred to as “autointoxication”). This hypothesis is based on medical beliefs of the Ancient Egyptians and Greeks.

Objective /aim To assess the safety, effectiveness and cost-effectiveness of colon hydrotherapy for body detoxification, constipation, irritable bowel syndrome and diverticulosis.

Results and conclusions The search strategies yielded 2 articles concerning the U.S. Food and Drug Administration (FDA) premarket notifications for devices used in colon cleansing and one article issued by the Texas Attorney General. There were seven articles (case series / case report/cross sectional studies) related to the adverse events of colon hydrotherapy. As for the effectiveness, one technology review and three cross sectional studies were retrieved.

In the United States of America the treatments are approved by the FDA for patients only when medically indicated, such as prior to undergoing radiologic or endoscopic examination.

There was poor level of evidence to suggest that commercial colonic hydrotherapy performed by individuals themselves or by alternative medicine practitioners may lead to adverse events such as colon or rectal perforations, abscess, perineal gangrene, abdominal pain, abdominal cramps, distended abdomen, rectal bleeding, outbreaks such as amebiasis and death.

There was also poor level and insufficient evidence to suggest the effectiveness of colon hydrotherapy for constipation, irritable bowel syndrome and faecal incontinence. There was no retrievable evidence on the cost-effectiveness of colon hydrotherapy. Colon hydrotherapy should be performed by experienced and trained practitioners. The practice should be regulated.

Recommendation Based on the above review, more high quality clinical research is warranted for various application of this technology in different conditions such as constipation, irritable bowel syndrome and faecal incontinence. Hence, commercial use of colon hydrotherapy when

iv not medically indicated cannot be recommended until more high quality evidence is available.

Methods Electronic databases which included PubMed, Ovid Medliner from 1950 to May week 2 2009, EBM Reviews-Cochrane Central Register of Controlled Trials, EBM Reviews- Cochrane database of systematic reviews, EBM Reviews-HTA Databases, Horizon Scanning database (Euro scan, Australia and New Zealand Horizon Scanning, defra), FDA website, MHRA, and Google were searched for published reports. There was no limit in the search. Relevant articles were critically appraised using Critical Appraisal Skills Programme (CASP) and evidence graded using US / Canadian Preventive Services Task Force.

COLON HYDROTHERAPY AN UPDATE

1. INTRODUCTION

The colon is the last portion of the digestive system in most vertebrates. In mammals the colon consists of four sections: the ascending colon, the transverse colon, the descending colon and the sigmoid colon. The colon measures approximately 1.5 meters in length. It is mainly responsible for storing waste, reclaiming water, maintaining the water balance and absorbing some vitamins, such as vitamin K.1

Colon cleansing (colon therapy) encompasses a number of alternative medical therapies intended to remove faecal waste and unidentified toxins from the colon and the intestinal tract. Colon cleansing may take the form of colon hydrotherapy (also called colonics or colonic irrigation) or oral cleansing regimens.2 Colon hydrotherapy uses enemas to inject water, sometimes mixed with herbs or other liquids, into the colon using special equipment. Oral cleansing uses dietary fibre, herbs, dietary supplements or laxatives. Practitioners believe colon cleansing removes accumulation of faeces from the walls of the large intestine which are believed to putrefy, harbour parasites or pathogenic gut flora to cause non specific symptoms and general ill-health (referred to as “autointoxication”). This hypothesis is based on medical beliefs of the Ancient Egyptians and Greeks.2

Colon hydrotherapy or colonic irrigation has its roots in ancient Egypt, Greece and India and has been used in Western world since the 1800s. It has formed an important part of traditional medicine. An individual may either choose to perform the colonic treatment on his own by purchasing a home colonic kit, or he may go to a colon hydrotherapy clinics. Treatments are usually given in a clinic or spa and sessions lasts 30 to 50 minutes. Practitioners should be qualified and a member of a recognised professional association such as International Association for Colon Hydrotherapy (I-ACT), Australian Colon Hydrotherapy Association (ACHA) in Australia or Association and Register of Colon Hydrotherapists (ARCH) in the United Kingdom (U.K.).3

Rectal irrigation also known as trans-anal irrigation is a way of emptying the lower bowel. It has been found to empty stool as far up as the splenic flexure. In the U.K., it must be prescribed and conducted by medically trained personnel. Indications of use are such as in neurogenic bowel disfunction; for example spinal cord injury, spina bifida and multiple sclerosis. It is also indicated for chronic constipation and chronic faecal incontinence.4

This technology review was conducted following a request from the Director of Kampar Hospital, Perak.

2. OBJECTIVE /AIM

The objective of this systematic review was to assess the safety, effectiveness and cost- effectiveness of colon hydrotherapy for use in conditions such as constipation, irritable bowel syndrome, diverticulosis and body detoxification.

3. TECHNICAL FEATURES

Colon Hydrotherapy Colonic treatment is now used in the U.K. as a naturopathic modality and it is claimed to be useful in treating:- Primary bowel conditions such as Irritable Bowel Syndrome (IBS) and constipation where the bowel can be normalised through the water temperature variation during treatment Some organic disease states such as diverticulosis (diverticulitis in remission) where regular elimination is important. Bowel transit time is improved Many secondary conditions, especially those affecting the other eliminative organs (skin, urinary tract and lungs) where they are accompanied by poor bowel mechanics Body detoxification, when it is accompanied by dietary measures5

It was claimed that the benefits of colonic irrigation through colon hydrotherapy can often be quickly observed in the form of improved bowel function together with clearer skin, more mental clarity and fewer headaches.5

There is no special preparation needed before the colonic treatment, although large meals and lots of fluids are not advised. The first appointment includes history taking, explaining the procedure and the treatment itself. A brief rectal examination must be carried out followed by an introduction of a speculum 1.5 inches (4 cm) is introduced to open the sphincter. An inlet and outlet tube is attached to the outside of the speculum, to open the system, with water going in and waste out. The waste is piped away. About 60 litres of water are used per treatment, but only small amounts are allowed to enter the bowel at any one time, acting to dilate the lower bowel, stimulating the bowel to empty itself. In all, about 15 litres enters the bowel during treatment, and the vast majority also comes out again.5

The water pressure is carefully controlled and is in fact lower than is normally generated during a bowel movement. At first, water is filled into the lower bowel with the client lying on the left side, then after about 10 minutes, the therapist would asked the client to lie on the client‟s back and using gentle massage techniques across the bowel to assist the elimination of waste and gas pockets. Some herbal infusions may be used during colonic treatment and a probiotic (friendly bacteria) may be given if it is indicated.5

The number of treatment varies depending on individual. It may vary from only one to several treatments spread out over a period of time, after which preventive or maintenance treatments may be recommended. It is claimed that all the equipment used is either disposable or sterilised using hospital-approved sterilizer or regularly serviced autoclaves.5

This procedure cannot be performed in conditions such as; during active infections and active inflammation (diverticulitis, Crohn‟s disease, ulcerative colitis), painful fissure or painful haemorrhoids until they are healed or in remission. Diseases such as congestive heart disease, severe uncontrolled hypertension, severe anaemia, liver scirrhosis, kidney disease, colo-rectal carcinoma are also absolute contraindications for this treatment. The other contraindications include physical conditions such as severe abdominal or inguinal hernias which cannot be usually reduced.5

There are two types of colonic machines that are commonly used today. The closed- tube system otherwise known as the closed system and the other is an open-basin system, more commonly known as open system. Various colonic clinics may be employing either one or both.6

With the closed system, water is allowed to flow into the colon through one of the two hoses connected to a tube that is inserted into the rectum, called the speculum. The water pressure can be regulated so as not to inconvenience the patient as well as cause any damage to the organ. The second hose is used to remove the water and wastes from the colon, pass through an illuminated glass viewing tube that enables viewing of the eliminated wastes and finally into the sewer system.6

Closed system

The open system on the other hand, has a treatment table that has a built in basin that is pumped directly to the sewer system. The water is introduced into the colon through the rectum, using a smaller tube that is as big as a pencil. The water can also be regulated just like in the closed system. However, unlike the closed system, open system encourages natural elimination of the water and wastes.6

Open system

4. Methodology

4.1. Searching Electronic databases were searched, which included PubMed, Ovid Medline(R) from 1950 to May week 2 2009, EBM Reviews-Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane database of systematic reviews, EBM Reviews - HTA Databases, Horizon Scanning database (Euro Scan, Australia and New Zealand Horizon Scanning, defra), FDA website, MHRA, and Google for published reports. There was no limit in the search. Additional articles were identified from reviewing the bibliographies of retrieved articles.

The search strategy used the terms which were either used singly or in various combinations; “colonic irrigation”, “colon irrigation”, “colonic hydrotherapy”, colon AND hydrotherapy, “colon hydrotherapy”, and haemorrhoid.

4.2. Selection All published articles related to safety, effectiveness and cost-effectiveness of colon hydrotherapy/colonic hydrotherapy/ colon irrigation/colonic irrigation were included. Articles related to rectal irrigation were not included. Relevant articles were critically appraised using Critical Appraisal Skills Programme (CASP) and evidence was graded according to US/Canadian Preventive Services Task Force (Appendix 1)

5. RESULTS AND DISCUSSION

The search strategies yielded 2 articles concerning the U.S. Food and Drug Administration (FDA) premarket notifications for devices used in colon cleansing and one article issued by the Texas Attorney General. There were seven articles (case series / case report/ cross sectional studies) related to the adverse events of colon hydrotherapy.

One technology review and three cross sectional studies related to the effectiveness of the colon hydrotherapy were also retrieved.

5.1. SAFETY 9

In the United States of America (U.S.A), the purchase, possession and use of colon hydrotherapy equipment require physician approval and supervision, according to the state and the federal law. The treatments are approved by the FDA for patients only when medically indicated, such as prior to undergoing radiologic or endoscopic examinations. FDA does not approve the use of colonic cleansing for “general well-being” and for “re-energizing life”.7

Devices such as Pro-Fit™ disposable rectal speculum and Angel of Water colon hydrotherapy system received 510 (k) from FDA for colon cleansing when medically indicated, such as before radiological or endoscopic examination.8,9

There were seven articles related to the adverse events of colon hydrotherapy. Texas Attorney General U.S.A., claimed that there was one death and four serious injuries involving patients with perforated colons occurred in 2003 following colon hydrotherapy treatments.7 level III Handley D.V., Rieger N.A., Rodda D.J. in their letter to the editor reported three cases of rectal perforation following colonic irrigation which was administered by alternative practitioners to relieve chronic constipation and to “cleanse” or “clear out stale faeces”. None of these cases had primary colonic or rectal pathology. 10 level III

Ratnaraja N from Addenbrooke‟s Hospital, Cambridge, United Kingdom (U.K.) reported a case of extensive abscesses (paraspinal, ilio-psoas and pelvic) in a 30 year old woman following a colonic irrigation performed by a colonic hydrotherapist.11 level III Similarly, Tan MP and Cheong DM from Tan Tock Seng Hospital, Singapore reported a life- threatening perineal gangrene in a patient following colonic hydrotherapy performed by alternative medicine practitioner.12

Istre et al. reported an outbreak of amebiasis involving 36 cases in persons who previously had colonic irrigation therapy at a chiropractic clinic in Western Colorado, U.S.A, from June 1978 to December 1980 due to contamination of the colonic irrigation machine.13

Potisansakul et al. conducted a cross-sectional study among patients in general surgical outpatient clinic at Ramathibodi Hospital, Thailand between July 2005 and March 2006 to look into the practice of colonic hydrotherapy in Thai population. The complication involving rectal bleeding was found in two out of 91 patients (2.19%) who practiced colonic detoxification.14 level III

Koch et al. in his study in University Hospital Maastricht, Netherlands, looked into the effectiveness of colonic irrigation for treatment of persistent faecal incontinence and / or constipation after unsuccessful or partially unsuccessful Dynamic graciloplasty (DGP). He found that side effects of irrigation were reported in 61% of the patients; leakage of water after irrigation, abdominal cramps and distended abdomen. Seven (16%) of patients stopped the rectal irrigation; five because the results were unsatisfactory whereas the complaints resolved completely in the other two.15 level III

5.2. EFFECTIVENESS

One technology review and three cross sectional studies were retrieved. A technology review conducted by the Health Technology Assessment Unit, Ministry of Health in 2003 found that there was insufficient evidence on the effectiveness and safety of colon hydrotherapy.16 level 1

Taffinder et al. conducted a cross sectional study to ascertain the current practice of commercial colonic hydrotherapy in the U.K. A questionnaire was sent to all 80 practitioners registered with the Association of Colonic Hydrotherapists (ACH) of the U.K. The practitioners who responded were also asked to pass on 10 questionnaires with stamped addressed envelopes to a consecutive series of their clients which included SF- 36 self-administered scoring system and a satisfaction survey. However, the response rate was low. Only thirty-eight of the 80 practitioners (48.00%) responded and 242 of 800 (35.35%) questionnaires from the clients were returned to the authors. All the practitioners had a minimum period of one year training with a hydrotherapist registered with ACH and had passed a written and practical examination. The average time of practice was six years. Twelve of 38 (32%) had clinical background (doctor, dentist, nurse). The mean number of hydrotherapy sessions they had conducted was self- estimated at 3,200 ranging from 140 to 10,000 sessions. On the average, 68 (range 4-200) sessions were performed monthly. Each treatment took about 30 to 60 minutes. The clients age ranged from 18 to 82 years (mean age was 44 years) and 84% were female. They had undergone an average of 35 hydrotherapy treatments with a range of 1to 2500 treatments with a median frequency of 10treatments per annum. They had lower SF-36 scores compared to the U.K. norm and 19% of the clients admitted having suffered depression and few had bipolar and eating disorders. Twenty-four percent of the clients complained of constipation and 29% had been diagnosed as irritable bowel syndrome. They reported high level of satisfaction with the hydrotherapy (satisfaction score; 75 per 100) and low level of satisfaction (satisfaction score; 25 per 100) with traditional treatment. However, the authors did not mention what was the traditional treatment. 17 level III

Similarly, Potisansakul et al. conducted a cross-sectional study among patients in general surgical outpatient clinic at Ramathibodi Hospital, Thailand between July 2005 and March 2006 to look into the practice of colonic hydrotherapy in Thai population. One thousand nine hundred and thirty nine questionnaires were distributed to the patients and were returned. The prevalence of colonic detoxification in the general outpatient clinic was 91 per 1,939 (4.68%). Female patients performed colonic detoxification much more often than male patients (83.52% versus 16.48%). The mean age of patients who performed colonic detoxification was 50.04 ± 11.25 years (22-71 years). The most commonly used substance for colonic detoxification was coffee (90.11%) followed by lemon juice (4.40%), pure water (3.30%), electrolyte fluid (4.40%) and normal saline solution (1.10%). The majority of patients performed the procedures by themselves (73.63%) and the frequency was 1 to 5 times per month (26.37%). Seventy eight percent of patients felt better, while 17.58% felt the same and 4.40% felt worse after the

procedure. The better feelings were described as easy defecation, improvement of dyspeptic symptom, increased appetite and improve skin texture. The worse feelings were described as dizziness, abdominal pain, urinary frequency, and increased bowel movement. Patients who performed colonic detoxification had more colorectal problems than those who did not, but this was not statistically significant; risk ratio was 1.35 (95% CI = 0.82 to 2.22, p-value = 0.241). In subgroup analysis, cancer was the significant factor in patients who performed colonic detoxification; risk ratio was 1.55 (95% CI = 1.13 to 2.14, p-value = 0.011).14 level III

The effectiveness of colonic irrigation for treatment of persistent faecal incontinence and/or constipation after unsuccessful or partially unsuccessful Dynamic graciloplasty (DGP) was investigated by Koch et al. in Netherlands. Patients with defecation disorders after DGP visiting the outpatient clinic of the University Hospital Maastricht, in the Netherlands were selected for colonic irrigation as additional therapy or salvage therapy in the period between January and June 2003. The Biotrol Irrimatic® pump or irrigation bag was used for colonic irrigation. The study included 46 patients with a mean age of 59.3± 12.4 years and 80% were female. Fifty-two percent of the patients used the irrigation as additional therapy for faecal incontinence, 24% for constipation and 24% for both. Overall, 81% of patients were satisfied with the irrigation. Thirty seven percent of the patients who initially had faecal incontinence became continent, while the rest (37% sometimes incontinent, 21% reported no change and the remainder 5% often incontinent). The problem was completely resolved in 30% of patients who initially had constipation. However, 50% of the patients sometimes had constipation, 10% had no change and the remainder 10% often had constipation.15 level III

The three studies described above were of poor level of evidence and varied in terms of methodology, target populations and also outcome measured. A high quality clinical trial is required to answer this therapeutic question for the various indications applied.

5.3. COST- EFFECTIVENESS

There was no retrievable evidence on the cost-effectiveness of colon hydrotherapy. However, Taffinder et al. in his cross sectional study of colonic hydrotherapy in the U.K. found that the cost varied from ₤50 to ₤80 per session.17 level III 5.4. ORGANISATION

5.4.1. Training and registration

In the U.K. and Australia colon hydrotherapy is usually performed by colon hydrotherapists. The Association and Register of Colon Hydrotherapists (ARCH) (formerly known as the Colonic International Association) in the U.K. was founded in 1987 by Dr Milo Siewert as a professional association of qualified therapists. The association maintain the register of therapists, offer a recognised process to colleges where colon hydrotherapy is taught, carry out premise inspection and develop protocols.18

There are three mandatory requirements for membership to ARCH: 18 i. Should have successfully completed and hold a pass certificate from an ARCH recognised training course in Colon Hydrotherapy AND ii. Applicants should be a fully qualified Doctor of Medicine or Registered General Nurse or should have taken and successfully completed a course of at least two years full-time or three years part-time duration in a substantial body- based therapy, including in-depth anatomy and physiology and hold a verifiable pass certificate and this therapy should have been practiced for at least two years. iii. The premise should reach the required standards upon inspection by ARCH

ARCH does not accept graduates of I-ACT colonic hydrotherapy courses since they are not taught ARCH syllabus or to their standards. They also do not accept into their membership students taught on self-administered open systems (e.g. Libbe, Jimmy-John), since they consider these are not therapeutic to the same level as therapist administering colonic hydrotherapy. They have safety concerns over the system. 18

Australia Colon Health Association (ACHA) was formed in 2002 and the first colon hydrotherapy association in Australia. ACHA focuses on closed system of colon hydrotherapy which correlates more to hygiene practices. It is established in medical institutions.They support therapists using the closed method of colon hydrotherapy.19

6. CONCLUSION

6.1. SAFETY

6.2. EFFECTIVENESS

There was poor level and insufficient evidence to suggest the effectiveness of commercial colon hydrotherapy:- i. For constipation, irritable bowel syndrome and colorectal problems either performed by colon hydrotherapists or performed by the individuals themselves. ii. For persistent faecal incontinence or constipation after unsuccessful or partially successful Dynamic graciloplasty.

6.3. COST- EFFECTIVENESS

There was no retrievable evidence on the cost-effectiveness of colon hydrotherapy.

6.4. TRAINING

Colon hydrotherapy should be performed by experienced and trained practitioners. The practice should be regulated.

7. RECOMMENDATION

Based on the above review, more high quality clinical research is warranted for various application of this technology in different conditions such as constipation, irritable bowel syndrome and faecal incontinence. Hence, commercial use of colon hydrotherapy when not medically indicated cannot be recommended until more high quality evidence is available.

8. REFERENCES

1. Colon (anatomy) – Wikipedia, the free encyclopedia. Available at http://en.wikipedia.org/wiki/Colon_(anatomy)

2. Colon cleansing – Wikipedia, the free encyclopedia. Available at http://en.wikipedia.org/wiki/Colon_cleansing

3. Colonic Irrigation, Colon Irrigation Clinics – Natural Therapy Pages. Available at http://www.naturaltherapypages.com.au/natural_medicine/Colon_Irrigation

4. Christian Norton. The Burdett Institute of Gastrointestinal Nursing. St. Mark‟s Hospital, London. Guidelines for the use of rectal irrigation (Healthcare Professionals).2007

5. Colonic Irrigation UK/Colonic Treatment & Therapists UK. Available at http://www.colonic-association.org/hydrotherapy.htmal

6. Colon Hydrotherapy- The Difference Between the Closed System and the Open System. Available at http://www.articlesbase.com/alternative-medicine-articles/colon- hydrotherapy-the-difference...

7. Texas Attorney General. Attorney General of Texas Greg Abbott. Attorney General Abbot Sues „Colonic Hydrotherapy‟ Providers for Abuse of medical devices ; One death reported. Available at http://www.oag.state.tx.us/oagnews/release.php?id=295

8. Premarket Notification: Pro Fit Disposable Speculum with Insertion Stopper. 510(k) Summary. Available at http://www.fda.org

9. Premarket Notification: Angel of Water™ Colon Hydrotherapy System. 510(k) Summary. Available at http://www.fda.org

10. Handley DV, Rieger NA, Rodda DJ. Rectal perforation from colonic irrigation administered by alternative practitioners. MJA. 2004;181(10):575-576

11. Ratnaraja N, Raymong N. Extensive abscesses following colonic hydrotherapy. Available at http;//infection. the lancet.com. 2005; 5:527

12. Tan MP, Cheong DM. Life-threatening gangrene from rectal perforation following colonic hydrotherapy: a case report. Ann Acad Med Singapore. 1999;28(4):583-585

13. Istre GR, Kreiss K, Hopkins RS et al. An outbreak of amebiasis spread by colonic irrigation at a chiropractic clinic. The New England Journal of Medicine. 1982;307:339- 342

14. Potisansakul N, Wilasrusmee C, Panichvisai S et al. Colonic detoxification among patients attending general surgical clinics: An epidemiological study. J Med Assoc Thai.2007;90(11):2310-2314 15. Koch SM, Uludag O, Naggar KE et al. Colonic irrigation for defecation disorders after dynamic graciloplasty. Int J Colorectal Dis. 2008;32:195-200

16. Health Technology Assessment Unit. Technology Review Chelation Therapy and Colon Hydrotherapy.2003

17. Taffinder NJ, Tan E, Webb IG et al. Retrograde commercial colonic hydrotherapy. 2004;6: 258-260

18. The Association and Register of Colon Hydrotherapists UK. Available at http://www.colonic-association.org/theassociation.html

19. Australian Colon Health Association, AHCA, Colonic Irrigation, Goald Coast, Queensland. Available at http://www.colonhealthassociation.com/

9. APPENDIX

9.1 Appendix 1

DESIGNATION OF LEVELS OF EVIDENCE

I Evidence obtained from at least one properly designed randomized controlled trial.

II-I Evidence obtained from well-designed controlled trials without randomization.

II-2 Evidence obtained from well-designed cohort or case-control analytic studies, preferably from more than one centre or research group.

II-3 Evidence obtained from multiple time series with or without the intervention. Dramatic results in uncontrolled experiments (such as the results of the introduction of penicillin treatment in the 1940s) could also be regarded as this type of evidence.

III Opinions or respected authorities, based on clinical experience; descriptive studies and case reports; or reports of expert committees.

SOURCE: US/CANADIAN PREVENTIVE SERVICES TASK FORCE (Harris 2001)