1. Study Design - as a function of questions

Transcription

1 1. Study Design - as a function of questions Is there any added impact from adding interventions together as apposed to one intervention on its own? USID questions behind combination study design: In an area of high coverage but limited usage how much transmission reduction can be expected by adding in IRS? In areas where IRS is being conducted how much added transmission reduction can be added by usage of LLINs either with children under 5s or pregnant women? In areas where one or more IRS rounds have reduced transmission, can LLIN introduction sustain these gains if IRS is withdrawn? In areas with high perennial transmission, can high LLIN coverage reduce the need for IRS to one round.

2 IRS coverage of >80% in studies is close to operational realities LLIN coverage that is often in the range of 30-40% coverage Studies have shown that LLIN coverage much above 80% there is much less added protective gain. Need to consider quality and physical durability of LLINs are the key issues. LLIN residual insecticidal life is generally proven. LLIN physical durability is less than previously assumed.

3 These key questions. Say we are doing ongoing vector control with LLINs or with IRS and want studies to tell us of any added values, or not, of combining another intervention.

4 Effectiveness of LLINs and IRS is now a bigger issue than efficacy for studies. To answer this well studies need to consider the following potential tools individually or in combinations: IRS LL IRS DL LLIN DL is a different starting point as it is new and not currently incorporated within ongoing malaria control programmes but may answer some of the limitations seen with LLINs and IRS.

5 Do the SOFT factors significantly affect the effectiveness of LLINs and IRS: Also are there other approaches that can improve effectiveness of LLINs and/or IRS? Studies may need to include measurement of the efficacy of a package of interventions, i.e.. tools and IEC and usage instruction/validation, rather than just the intervention tools. Does combination of nets and IRS alone result in increased impact in comparison with nets + IRS + IEC/hang up. Or do we need to simply ensure that all combination studies include delivery criteria of IRS/LLIN IEC and LLIN hang up.

6 Does the sequence of intervention affect impact: Does starting with LLINs and adding IRS or starting with IRS and adding LLINs: Could study this with four arms: LLIN then add in IRS LLIN IRS then add in LLIN IRS

7 Study type: Generally a Cluster Randomised Design is likely to be the best feasible approach: Challenge: Is malaria control success becoming a limitation for study feasibility.

8 Future Challenge: We will need to study what tools are needed to mop up the last cases and maintain low transmission. Will today s tools be suitable when high transmission areas become low and epidemic?

9 Summary re study design: RCT Introducing 2nd Vector control tools in an area with ongoing VC tool Test absolute (=efficacy) impact of LLIN vs IRS vs combination Testing a new VC tool vs an existing tool. *considering the soft factor such as distribution / hang up/ and IEC

10 2. Duration: All phase 3 combination studies should ideally be a 2 years and there may be some advantages in 3 years studies in order to ensure we have a clear idea of durability and do not make assumptions about a tools durability. These will be more expensive but can be designed as studies with different phases: Phase 1: over a defined period (probably 2 years) adequate to give defined IMPACT INDICATORS. At the end of this study phase an analysis of those key outputs should be released to provide he evidence base to help advice programmatic usage. Phase 2: over an extended period of years to monitor other factors such as durability / impact of durability on usage / and a minimum monitoring of entomological/epidemiological indicators to advise on how impact changes over time (and provide for study stop indicators).

11 Sample size and power All trials need to be of adequate size and power to generate significant results There will be a trade off between size an duration Cluster balance, size and number will vary with setting. In areas of lower transmission - as a rule of thumb anything less than 10 per arm may not show small differences (superiority) with combinations and probably 15 is a reasonable guide for studies. Areas of very high transmission like DR Congo, Liberia etc cluster requirements are fewer and smaller Clusters need to be separated by adequate distance to minimize risk of spill over effects.

12 Where are combination trials are needed: Where currently planned and feasible Where Arabiensis is predominant as current tools may not impact on the vector much. Its coverage is expanding, especially as An. G reduces Can we reduce vector man contact with other tools.

13 Within the same area, the same tools may control one species more effectively than another. If we control a leading species, will transmission continue via another species. Will it increase over time as other vectors become more efficient? Generally studies should include these end points. Need to run combination studies in Gambiense areas Need to run combination studies in Funestus areas Studies to measure the value of combinations of tools in areas where vectors (same species or multiple species) bite indoors or outdoors (but may rest indoors) Studies in areas where vectors are known to bite and rest outdoors more exclusively (W. Africa? and Asia).

14 Studies - Resistance If used properly can IRS be used as a resistance management tool in combination with LLINs or other tools / insecticide classes? (Hemingway, E. Mexico, old study). Future reliance on IRS + LLINs in combination would be a very expensive route for resistance management. Can combinations of insecticides (class or mode of action) on material weaves manage resistance? This should be explored and would be a more efficient and cheaper route if feasible. Agri. Industry needs to be consulted further to see if they have other resistance management planning tricks/models.