Data Monitoring Committees and clinical trials: From scientific justification to organisation.

Clinical trials often last several months or even several years. As the trial progresses, it can be tempting to find out whether the data obtained already answers the question posed at the start of the trial in order to stop inclusions or monitoring earlier. However, knowing and taking into account interim results can sometimes compromise the integrity of the results, which is counterproductive. To minimise this risk and ensure that the treatments are assessed reliably, safety and/or efficacy criteria are monitored during the study by a Data Monitoring Committee. After receiving the results confidentially, the Data Monitoring Committee assesses the benefit/risk ratio of the study treatment and recommends that the trial be continued, modified or terminated. Data Monitoring Committee members issuing these recommendations have an important responsibility: a hasty decision to end the trial may lead to inconclusive results unable to answer the initial question and, inversely, delaying the decision to end the trial may expose the subjects to potentially ineffective or even harmful interventions. The Data Monitoring Committee's task is therefore particularly complex. With this in mind, the round table discussion at the Giens workshops was a chance to review the scientific justification for creating Data Monitoring Committees and to recall the need for their members to receive comprehensive training on the complexities of multiple analyses, confidentiality requirements applying to the results and the need for them to be aware that recommendations to end a trial must be based on data that is robust enough to assess the benefit/risk ratio of the treatment studied.

Prospective and multicentre study of radiofrequency treatment in anal fistula.

BACKGROUND: The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. METHODS: We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. RESULTS: Fifty patients with a mean age of 51 years (22-82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types (p: 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. CONCLUSION: Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial.

AIM: In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. METHODS: This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. RESULTS: Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). CONCLUSIONS: Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.