Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Trials”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed2000

Promotion of breastfeeding intervention trial (PROBIT): a cluster-randomized trial in the Republic of Belarus. Design, follow-up, and data validation.

This paper summarizes the objectives, design, follow-up, and data validation of a cluster-randomized trial of a breastfeeding promotion intervention modeled on the WHO/UNICEF Baby-Friendly Hospital Initiative (BFHI). Thirty-four hospitals and their affiliated polyclinics in the Republic of Belarus were randomized to receive BFHI training of medical, midwifery, and nursing staffs (experimental group) or to continue their routine practices (control group). All breastfeeding mother-infant dyads were considered eligible for inclusion in the study if the infant was singleton, born at > or = 37 weeks gestation, weighed > or = 2500 grams at birth, and had a 5-minute Apgar score > or = 5, and neither mother nor infant had a medical condition for which breastfeeding was contraindicated. One experimental and one control site refused to accept their randomized allocation and dropped out of the trial. A total of 17,795 mothers were recruited at the 32 remaining sites, and their infants were followed up at 1, 2, 3, 6, 9, and 12 months of age. To our knowledge, this is the largest randomized trial ever undertaken in area of human milk and lactation. Monitoring visits of all experimental and control maternity hospitals and polyclinics were undertaken prior to recruitment and twice more during recruitment and follow-up to ensure compliance with the randomized allocation. Major study outcomes include the occurrence of > or = 1 episode of gastrointestinal infection, > or = 2 respiratory infections, and the duration of breastfeeding, and are analyzed according to randomized allocation ("intention to treat"). One of the 32 remaining study sites was dropped from the trial because of apparently falsified follow-up data, as suggested by an unrealistically low incidence of infection and unrealistically long duration of breastfeeding, and as confirmed by subsequent data audit of polyclinic charts and interviews with mothers of 64 randomly-selected study infants at the site. Smaller random audits at each of the remaining sites showed extremely high concordance between the PROBIT data forms and both the polyclinic charts and maternal interviews, with no evident difference in under- or over-reporting in experimental vs control sites. Of the 17,046 infants recruited from the 31 participating study sites, 16,491 (96.7%) completed the study and only 555 (3.3%) were lost to follow-up. PROBIT's results should help inform decision-making for clinicians, hospitals, industry, and governments concerning the support, protection, and promotion of breastfeeding.

Adult↗
PubMed1994

Results of APL 91 European trial combining ATRA and chemotherapy: presentation of APL 1993 trial.

Initial results of ATRA in newly diagnosed APL showed that this drug was associated with a high complete remission (CR) rate but also (i) to a risk of hyperleukocytosis and of ATRA syndrome, (ii) to rapid relapse unless ATRA was followed by intensive chemotherapy. These findings prompted our group to design an approach combining ATRA and intensive chemotherapy in newly diagnosed APL, where chemotherapy could prevent relapses and also, in cases with increasing leukocyte counts, could prevent the ATRA syndrome. In a pilot study, this approach gave a high CR rate (96%) and (with now prolonged follow-up) a significant reduction in the incidence of relapse, as compared to a historical control treated with chemotherapy alone. The superiority of the combination of ATRA and chemotherapy over chemotherapy alone (especially for the incidence of relapse) was subsequently confirmed in a randomized European trial (APL 91 trial). We are now testing in a new European trial (APL 93 trial) whether chemotherapy should be administered with ATRA, or should follow ATRA during induction treatment, and whether maintenance therapy with intermittent ATRA, low-dose chemotherapy, or both can further reduce the risk of relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

The Alpha trial: European/Australian randomized double-blind trial of two doses of didanosine in zidovudine-intolerant patients with symptomatic HIV disease. Alpha International Coordinating Committee.

OBJECTIVES: To compare the efficacy and toxicity of two doses of didanosine (ddI) in patients with symptomatic HIV disease who are intolerant of zidovudine (ZDV). DESIGN: The Alpha trial is a randomized double-blind multicentre trial of two doses of ddI. ddI was given as one buffered sachet twice daily in doses adjusted for weight: 750 mg per day for patients > or = 60 kg in the higher-dose group, and 200 per day for the lower-dose group. RESULTS: Patients (n = 1775; 907 higher-dose, 868 lower-dose) from nine European countries and Australia were randomized and started trial treatment. Sixty per cent had AIDS, 65% had CD4 cell counts < 50 x 10(6)/l and 55% had received ZDV for more than 12 months. Follow-up was to death or 30 September 1992, and only 33 patients (20 higher-dose, 13 lower-dose) had been lost to follow-up for at least 3 months at that time. The longest follow-up was 28.5 months and the mean (SD) was 12.4 (6.9) months. There was no significant difference in survival between the groups: 67% of patients in each group died, the median survival being 13.0 months in the higher-dose and 12.5 in the lower-dose groups, a difference of about 0.5 months (95% confidence interval, -0.9 to 2.0; log-rank P = 0.7). There was also no significant difference in progression to AIDS or death, development of HIV encephalopathy or death, or development of new AIDS events or death. There were small (but statistically significant) differences in the changes in CD4 cell count and in p24 antigen levels between the groups, with greater increases in CD4 and greater decreases in p24 in the higher-dose group. There were also clear differences in adverse events: pancreatitis developed more frequently in the higher-dose group, 66 patients compared to nine patients in the lower-dose group, of whom 37 and six, respectively, were classified as definite cases. Nine cases (seven higher-dose, two lower-dose) were reported to have died because of or with pancreatitis. Peripheral neuropathy, abnormal liver function and dry mouth were also reported more often in the higher-dose group. CONCLUSIONS: The Alpha trial is not able to provide direct evidence for the clinical efficacy of ddI. There was no significant difference between the two doses in mortality or disease progression. However, the higher dose was more toxic.

Adult↗
PubMed1996

Response to treatment by multidrug regimens in the THELEP controlled clinical drug trials. Subcommittee on Clinical Trials of the Chemotherapy of Leprosy (THELEP) Scientific Working Group of the UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases.

During the period 1977-1983, clinical trials of five multidrug regimens were conducted among 215 patients with previously untreated multibacillary leprosy at the Institut Marchoux, Bamako, Mali, and the Central Leprosy Teaching and Research Institute, Chingleput, South India. The trials were designed primarily to permit measurement of the proportions of persisting Mycobacterium leprae in the patients' skin lesions. In addition, the combination of the large number of patients studied, the large volume of carefully standardized data, and the employment of multidrug regimens provided a unique opportunity to measure the clinical response of patients to treatment by these regimens. Persisting M. leprae were detected in 7.8% of all specimens; the frequency did not vary with centre, regimen, or duration of treatment. The bacterial index (BI) decreased by a mean annual rate of 75%, the logarithmic biopsy index by a mean annual rate of 87%, and the logarithm10 number of acid-fast bacilli per g tissue by a mean annual rate of 69%. The rate of decrease of these measures of the numbers of M. leprae was related to the 'strength' of the regimen. Although no difference of clinical status as a function of regimen was demonstrated, a difference was observed between the two centres, probably the result of different clinical criteria employed by the responsible physicians. A change of histopathological classification in the course of the trials was recorded for 12% of the patients, most representing upgrading from LLs to BL, without relation to regimen or treatment centre. ENL was less severe for the patients treated by the maximal regimen in Chingleput, which included daily clofazimine; as expected, the majority of patients treated by this regimen were found to have maximal pigmentation. Prednisolone was evidently preferred for treatment of ENL in Chingleput, whereas thalidomide was preferred in Bamako. Fourteen cases of jaundice were observed, primarily among the patients treated by the maximal regimens, that included daily administration of rifampicin for the entire two years of the trials. Measurements of weight and blood pressure, and studies of the blood and of hepatic and urinary tract function revealed only negligible differences among regimens and between centres. In many cases, those differences that were observed were associated with ENL.

Drug Therapy, Combination↗
PubMed1997

CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group.

BACKGROUND: Aspirin is effective in the treatment of acute myocardial infarction and in the long-term prevention of serious vascular events in survivors of stroke and myocardial infarction. There is, however, no reliable evidence on the effectiveness of early aspirin use in acute ischaemic stroke. METHODS: The Chinese Acute Stroke Trial (CAST) was a large randomised, placebo-controlled trial of the effects in hospital of aspirin treatment (160 mg/day) started within 48 h of the onset of suspected acute ischaemic stroke and continued in hospital for up to 4 weeks. The primary endpoints were death from any cause during the 4-week treatment period and death or dependence at discharge, and the analyses were by intention to treat. 21,106 patients with acute ischaemic stroke were enrolled in 413 Chinese hospitals at a mean of 25 h after the onset of symptoms (10,554 aspirin, 10,552 placebo). 87% had a CT scan before randomisation. It was prospectively planned that the results would be analysed in parallel with those of the concurrent. International Stroke Trial (IST) of 20,000 patients with acute stroke from other countries. FINDINGS: There was a significant 14% (SD 7) proportional reduction in mortality during the scheduled treatment period (343 [3.3%] deaths among aspirin-allocated patients vs 398 [3.9%] deaths among placebo-allocated patients; 2p = 0.04). There were significantly fewer recurrent ischaemic strokes in the aspirin-allocated than in the placebo-allocated group (167 [1.6%] vs 215 [2.1%]; 2p = 0.01) but slightly more haemorrhagic strokes (115 [1.1%] vs 93 [0.9%]; 2p > 0.1). For the combined in-hospital endpoint of death or non-fatal stroke at 4 weeks, there was a 12% (6) proportional risk reduction with aspirin (545 [5.3%] vs 614 [5.9%]; 2p = 0.03), an absolute difference of 6.8 (3.2) fewer cases per 1000. At discharge, 3153 (30.5%) aspirin-allocated patients and 3266 (31.6%) placebo-allocated patients were dead or dependent, corresponding to 11.4 (6.4) fewer per 1000 in favour of aspirin (2p = 0.08). INTERPRETATION: There are two major trials of aspirin in acute ischaemic stroke. Taken together, CAST and the similarly large IST show reliably that aspirin started early in hospital produces a small but definite net benefit, with about 9 (SD 3) fewer deaths or non-fatal strokes per 1000 in the first few weeks (2p = 0.001), and with 13 (5) fewer dead or dependent per 1000 after some weeks or months of follow-up (2p < 0.01).

Acute Disease↗
PubMed1998

Results of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and an update on trials now in progress.

Bezafibrate is a latest generation fibrate derivative that substantially reduces total plasma cholesterol and triglyceride concentrations and increases high density lipoprotein (HDL) cholesterol. The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was a double-blind, placebo-controlled trial over 5 years to assess the angiographic benefits of bezafibrate retard (400 mg. day (-1) in young, male, post-myocardial infarction (post-MI) patients. The trial demonstrated that without lowering serum low density lipoprotein cholesterol, progression of coronary atherosclerosis was prevented and the coronary event rate reduced. In subgroup analyse, bezafibrate decreased the rate of progression of coronary atherosclerosis and coronary event rate in young post-MI patients, primarily by slowing the progression of mild-to-moderate lesions. Additional studies are underway to explore further the benefits of this fibrate in coronary heart disease. The Bezafibrate Infarction Prevention study is the first trial to investigate the effects of raising HDL cholesterol and lowering triglycerides in patients with established coronary disease. The Lower Extremity Arterial Disease Event Reduction study is assessing the benefit of lowering fibrinogen in the prevention of major ischaemic heart disease and stroke in patients with peripheral vascular disease.

Adult↗
PubMed1990

Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer: dietary compliance in the Women's Health Trial Vanguard Study.

The Women's Health Trial Vanguard Study was conducted to examine the feasibility of a nationwide, randomized multicenter intervention trial to test the hypothesis that a low-fat diet followed for a period of 10 years will reduce breast cancer risk. Women ages 45-69 years at increased risk of breast cancer were randomized into intervention (low-fat diet, n = 184) and control (usual diet, n = 119) groups. On the basis of 4-day food records, baseline fat intakes were comparable in the two groups, averaging 1,718 kcal with 39% of energy as fat. Intervention women reported substantially lower fat intake at 6 (20.9% kcal), 12 (21.6%), and 24 months (22.6% kcal). In contrast, control women reported only slight reductions in fat intake (37.3% kcal at 12 months and 36.8% kcal at 24 months). Evidence that these women were indeed complying with the low-fat dietary intervention comes from (a) the reasonable nature of reported nutrient changes within food groups in the intervention women and (b) agreement between observed and expected differences in plasma total cholesterol between the control and the intervention groups. At 12 months, the observed control - intervention plasma cholesterol difference was 13.1 +/- 4.6 mg/dl while the expected difference based on the Keys equation was 15.1 +/- 1.1 mg/dl; at 24 months, the observed difference was 15.5 +/- 4.3 mg/dl and the expected difference was 12.0 +/- 1.2 mg/dl. These analyses indicate that the intervention women made substantial dietary changes and have successfully maintained these changes over a 2-year period. This study thus demonstrates the feasibility of a randomized trial with an intensive low-fat dietary intervention.

Aged↗
PubMed1996

Are more antiemetic trials with a placebo necessary? Report of patient data from randomized trials of placebo antiemetics with cisplatin.

BACKGROUND: Because of the predictability of significant emesis after its use, cisplatin serves as the standard emetic stimulus for trials of antiemetic drugs. To define better the incidence, severity, and pattern of emesis that follows cisplatin, facilitate the testing of new agents, and obviate the need for further placebo-controlled trials for this indication, individual patient data were compiled from completed studies with placebo antiemetics and cisplatin. METHODS: The time and number of emetic episodes during the 24 hours after cisplatin were obtained for 48 patients given a placebo antiemetic. Each was treated as part of a randomized, double-blind trial reported between 1981 and 1990. Emesis after antiemetic "rescue" therapy was also assessed. RESULTS: Emesis occurred in 47 of 48 patients (98% observed rate, 95% confidence interval, 89-99%). The median number of emetic episodes during the 24 hours after cisplatin was 6. Emesis continued after rescue in 77% of patients. CONCLUSIONS: Cisplatin caused severe emesis that persisted despite rescue in placebo-treated patients. Using the data presented, any therapy preventing acute emesis in 8 or more of the 48 individuals receiving cisplatin > 50 mg/m2 was an active antiemetic (P = 0.05). The four trials discussed here documented the antiemetic effectiveness of granisetron, metoclopramide, and ondansetron. The placebo-treated patients studied can serve as a control group for testing new therapies. Because of the certainty of severe emesis after cisplatin, and the availability both of these data and several proven drugs for this condition, prospective comparisons of antiemetics should employ active control medications.

Adult↗
PubMed2001

Mid-trial design reviews for sequential clinical trials.

When sequential clinical trials are conducted by plotting a statistic measuring treatment difference against another measuring information, power is guaranteed regardless of nuisance parameters. However, values need to be assigned to nuisance parameters in order to gain an impression of the sample size distribution. Each interim analysis provides an opportunity to re-evaluate the relationship between sample size and information. In this paper we discuss such mid-trial design reviews. In the special cases of trials with a relatively short recruitment phase followed by a longer period of follow-up, and of normally distributed responses, mid-trial design reviews are particularly important. Examples are given of the various situations considered, and extensive simulations are reported demonstrating the validity of the review procedure in the case of normally distributed responses.

Cardiovascular Diseases↗
PubMed2006

Beyond randomized controlled trials: a critical comparison of trials with nonrandomized studies.

Observational analogs of randomized clinical trials (RCTs) are well accepted in the study of disease risk factors, diagnosis, and prognosis. There is controversy about observational studies when the focus is on the intended benefit due to lack of blinding and poor control for unmeasured confounding. Well-designed randomized clinical trials are costly both in time and money. Therefore, existing databases are used increasingly and are often the only feasible source with which to examine delayed health effects. We reviewed the reasons for possible discrepancies between RCTs and observational studies. There can be different patient populations, differences in therapeutic regimen, control of confounding, follow-up, measuring outcome, and differences arising from the intention-to-treat analysis. Observational studies cannot replace trials, nor do trials make observational studies unnecessary. Both designs are susceptible to particular bias, so neither provides perfect information.

Observation↗
PubMed2007

Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer multi-slice CT screening trial (NELSON).

A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit 15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = +/-4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation.

Aged↗
PubMedDate not supplied

The use of surrogate endpoints in clinical trials: focus on clinical trials in cardiovascular diseases.

Surrogate endpoints include a wide range of laboratory or physical measurements used in clinical trials as a substitute for meaningful clinical endpoints that directly assess effects of the intervention(s) tested on mortality and/or morbidity. These surrogate endpoints are frequently employed in clinical trials and when used judiciously, can accelerate and focus the study of new therapies and can greatly enhance our understanding of their mechanisms of action. The current review provides a definition of surrogate endpoints, proposes practical criteria for establishing their validity, outlines some of the advantages, disadvantages and specific statistical considerations associated with their use in clinical trials and attempts also to highlight drug approval issues associated with the use of these endpoints. A number of examples are also provided related to the use of surrogate endpoints in clinical trials with special emphasis on their use in cardiovascular medicine.

Cardiovascular Diseases↗
PubMed1980

Drug trials in myocardial infarction. Lessons to be learned from the Anturane Reinfarction Trial.

Drug intervention trials in myocardial infarction are unlikely to prove an effect unless planning takes into consideration: (1) the multiple causes for cardiac mortality after myocardial infarction, and the likelihood that the drug being tested is unlikely to affect all of these causes; (2) the different mortality rates at different periods following the qualifying infarct; (3) the contribution of each cause to the total mortality encountered during each period; and (4) the elimination of the various dilution factors which plague those trials based only on an intention to treat rather than on the efficacy of the drug when administered properly to eligible patients. Prospective studies should be designed with these points in mind. Otherwise one will be confronted with the usual criticisms and scepticism associated with a retrospective analysis. In this regard, the Anturane Reinfarction Trial represents an advance in trial design, and the lessons to be learned from it provide a basis for further improvements.

Clinical Trials as Topic↗
PubMed2006

[Operative standardization in randomized controlled surgical trials. Meeting of the INSECT trial].

BACKGROUND: INSECT is an internationally registered, three-armed, multicentre, intraoperatively randomised model trial of the Study Centre of the German Surgical Society. The interventions being compared are running suture technique with slowly absorbable monofilament suture material (PDS vs MonoPlus) and interrupted technique with a braided, rapidly absorbable suture material (Vicryl). The primary endpoint is the rate of incisional hernias 1 year postoperatively. MATERIAL AND METHODS: A total of 25 surgeons from 24 different institutions at all levels of care evaluated the theoretical and practical sessions of the surgical investigator meeting using 25 criteria, including course organisation, content, and speaker evaluation, and a categorical grading system from 1 (very good) to 6 (insufficient). RESULTS: Distribution of the 625 grades was: very good (1) n=367, good (2) n=207, satisfactory (3) n=39, adequate (4) n=2, and "No statement" n=10. The average score for the investigator meeting was 1.5. CONCLUSION: The participants felt they were successfully prepared theoretically and practically for trial interventions and conduct by attending the meeting. Clear explanation of the measures for treatment equivalence before and during trials is mandatory in randomised controlled surgical trials.

Abdominal Wall↗
PubMed1994

Development of Design-a-Trial, a knowledge-based critiquing system for authors of clinical trial protocols.

Many published clinical trials are poorly designed, suggesting that the protocol was incomplete, disorganised or contained errors. This fact, doctors' limited statistical skills and the shortage of medical statisticians, prompted us to develop a knowledge-based aid, Design-a-Trial, for authors of clinical trial protocols. This interviews a physician, prompts them with suitable design options, comments on the statistical rigour and feasibility of their proposed design and generates a 6-page draft protocol document. This paper outlines the process used to develop Design-a-Trial, presents preliminary evaluation results, and discusses lessons we learned which may apply to the developed of other medical decision-aids.

Clinical Trials as Topic↗
PubMed1993

Performance evaluation in multicenter clinical trials: development of a model by the AIDS Clinical Trials Group.

The AIDS Clinical Trials Group (ACTG), supported by the National Institute of Allergy and Infectious Diseases (NIAID), is the largest federally funded program of AIDS clinical trials. It is a collaboration involving 59 institutions and affiliated clinical centers, known as AIDS Clinical Trials Units (ACTUs), NIAID staff, and a Statistical and Data Analysis Center (SDAC). An institutional evaluation tool was developed to evaluate ACTU performance, distinguish between clinical centers with superior performance and those not meeting standards, and assist NIAID in allocating funding based on performance. The evaluation tool was designed to reflect the many distinguishing features of ACTG study protocols and clinical trial centers in order to measure performance objectively. The evaluation focused on assessing the financial resources expended by the ACTU in recruiting, treating, and following study patients during the evaluation period; the number of women and minorities enrolled; and the ACTU's scientific contributions to the ACTG. To help quantify the ACTU's performance in enrolling study subjects, a formula was derived to assess the total effort required to screen, enroll, treat, and assess subjects participating in ACTG studies. A weighting system was developed for each study protocol to account for the variations in effort and resources required by the different protocols. Future directions in the ACTG evaluation process include strategies to evaluate performance in relation to quality of data and to determine ways in which the evaluation process can be used to enhance the achievement of programmatic goals.

Acquired Immunodeficiency Syndrome↗
PubMed2005

INvestigation of STEnt grafts in patients with type B Aortic Dissection: design of the INSTEAD trial--a prospective, multicenter, European randomized trial.

PURPOSE: This study describes the design of an ongoing randomized trial initiated to compare the 2-year outcome of uncomplicated type B aortic dissection when treated by endovascular implantation of a Medtronic Talent stent graft adjunctive to best medical treatment versus best medical treatment alone. METHODS: Patients older than 18 years with type B aortic dissection as diagnosed by computed tomography or magnetic resonance angiography are randomized to either a thoracic aortic endoprosthesis and antihypertensive treatment, called "stent grafting," or a tailored antihypertensive treatment, called "medical treatment." Only patients in a clinically stable condition and without spontaneous thrombosis of the false lumen after 14 days of the index dissection are considered eligible for study inclusion. RESULTS: Primary outcome measure is all-cause mortality. Secondary outcome variables include conversion to stent and/or surgery, induced thrombosis of the false lumen, cardiovascular morbidity, aortic expansion (>5 mm/y of maximum diameter including true and false lumina), quality of life, and length of intensive care unit and hospital stay. The study design calls for 136 patients to be randomized and monitored for 24 months. CONCLUSIONS: The INSTEAD trial is the first randomized trial investigating the role of endoluminal treatment of uncomplicated type B aortic dissection. By the end of December 2004, 125 patients were randomized, accounting for 92% of the target. Final results of the INSTEAD trial should be available in 2006.

Aged↗
PubMed2006

Trial of management of borderline and other low-grade abnormal smears (TOMBOLA): Trial design.

Cervical screening reduces the risk of cervical cancer by detecting and treating cervical intraepithelial neoplasia (CIN). The management of women with low-grade cervical abnormalities is controversial. Two management policies exist: repeat smears in primary care and colposcopy examination. It is not clear which of these is the more effective and efficient. There is also uncertainty as to the most effective and efficient management of women at colposcopy when an area of abnormality is seen on the cervix - immediate treatment or biopsy and selective recall for treatment if the biopsy result suggests this is necessary. The result of a human papillomavirus (HPV) test might assist in deciding the appropriate management of women with low-grade abnormalities. TOMBOLA, a pragmatic randomised-controlled trial set within the cervical screening programmes in Scotland and England, addresses these three areas of uncertainty. Almost four and a half thousand women aged 20-59 with a low-grade cervical abnormality have been recruited and randomised to either repeat smears or colposcopy examination. Women in the colposcopy arm of the trial are further randomised to a policy of either immediate treatment or biopsy and selective recall for treatment if they have an abnormal transformation zone. Women are followed up to an exit examination at 3 years. HPV testing is undertaken at recruitment and at the exit examination. The primary endpoint is cumulative incidence of CIN2/3. A range of other clinical, psychosocial and economic outcomes is being considered. This paper describes the design of the trial, and discusses the rationale underlying aspects of the design and the challenges faced in designing and implementing the trial.

Alphapapillomavirus↗