Non-Interventional Post-Authorisation Safety Study (NI-PASS) as an effectiveness check of an additional Risk Minimisation Measure (aRMM) (Direct Healthcare Professional Communication [DHPC]) for Bendamustine

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

  Disease epidemiology

  Drug utilisation

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Cross-sectional

Population studied

• Short description of the study population:
  The study cohort included new users of bendamustine or similar alkylating drugs for treating indolent non-Hodgkin’s lymphoma (iNHL), chronic lymphocytic leukemia (CLL), or multiple myeloma (MM) during the pre-direct healthcare professional communication (DHPC) dissemination period (01 April 2015 – 31 March 2017) or the post-DHPC dissemination period (01 September 2017 – 31 August 2019).; the study included single patient in either the bendamustine cohort or the cohort of alkylating drugs similar to bendamustine in the same period. The included patients were expected to be indicative of patients in the general population.
• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  21091

Study design details

• Main study objective:
  To evaluate all-cause mortality and serious and fatal infections occurring in pre- and post-DHPC dissemination periods for new users of bendamustine and new users of other alkylating drugs similar to bendamustine, and to quantify and characterise approved- and off-label use of bendamustine and other alkylating drugs similar to bendamustine in new users in pre- and post-DHPC dissemination periods.
• Outcomes:
  -Study A: All-cause mortality, serious and fatal infections -Study B: Approved- and off-label use of bendamustine and alkylating drugs similar to bendamustine, -Study A: Hepatitis B reactivation, myelosuppression, use of anti-infective drugs, use of anti-infective drugs used for prophylaxis of opportunistic infections (PJP, VZV, CMV), frequency of laboratory testing for CD-4 positive T-cell levels in outpatient settings. -Study B: Concurrent use of bendamustine with rituximab, obinutuzumab, or idelalisib
• Data analysis plan:
  Study A: The incidence rates and corresponding 95% CIs of safety event outcomes will be calculated by dividing the number of observed events by person-time exposure. Results for the pre- and post- DHPC dissemination periods will be presented separately. The main study results will be stratified by country. Study B: The proportion of new users of bendamustine or alkylating drugs similar to bendamustine with any observed off-label use during the study period (pre- and post-DHPC dissemination separately) will be calculated by dividing the number of new users with any off-label use by the total number of new users, and 95% CI will be calculated. The proportion of new users of bendamustine or alkylating drugs similar to bendamustine with off-label use at the time of new use will be calculated together with 95% CIs. Results for the pre- and post-DHPC dissemination periods will be presented separately. The main study results will be stratified by country.