It has long been considered that longer application times when using head louse treatment lotions are more effective than shorter applications. This was demonstrated in vitro using insecticide based products in which the formulation vehicle evaporates and concentrates the active material on the louse surface. The same approach was initially taken with physically acting preparations such as 4% dimeticone lotion and preliminary results from a first small study did indicate that an 8 hour or overnight treatment was more effective than one of only 20 minutes . However, in a later study we found that, contrary to expectation, reducing the application time for 4% dimeticone spray gel to 15 minutes not only increased the effectiveness but appeared to be wholly effective with a single application .
Although the majority action of 4% dimeticone lotion is derived from the dimeticone being deposited in the insect spiracular and tracheal systems, resulting in blocking of water excretion , it is necessary for it to be carried there by the solvent component of the product. If the solvent does not deliver sufficient dimeticone to the target site the activity may be reduced.
The perceived advantage of the 4% dimeticone gel over the original 4% lotion is that the gel seems to adhere to the lice more effectively and, in the spray form, is easier to direct and control ensuring all lice are killed and those eggs close to hatching are inhibited from doing so, as was demonstrated in our earlier study in which the product gave 100% efficacy after the first application in that two application trial . In this study, most lice found by investigators during follow up assessments could be attributed to eggs that hatched after treatment, presumably because they had been missed as a result of inadequate spreading of the liquid gel using the dropper bottle. Some of the children had also been observed to present with hair dampened by sweat at the time of the treatment application, which may have acted as a barrier to the silicones forming a complete coating on some louse eggs, with the possible result that silicone was not able to reach the vulnerable surfaces of the eggs due to the presence of a water film. The four infestations in the ITT group without nymphs were all attributable to reinfestation from contacts either within the family or the local community.
This randomised controlled trial has clearly demonstrated a difference in overall activity between a physically acting preparation using a single application and two applications of an insecticide based product affected by insecticide resistance. Hitherto, the majority of claims that different products containing silicones, and other physically acting preparations, are effective with a single application have not been based on published clinical data but have been extrapolations either from in vitro data or else obtained in studies where the products were applied twice. This study has not only confirmed efficacy for a single application of Hedrin 4% dimeticone liquid gel, and demonstrated a difference in overall activity between a physically acting preparation and an insecticide based product affected by insecticide resistance, but has also demonstrated that extrapolations about treatment outcomes may be misleading, in the absence of clinical confirmation.
This trial has also provided the first clear evidence that louse eggs do not all hatch within 7 days (Table 2). We and many other investigators in the past had assumed this hatching period primarily because previously we had no other experimental evidence upon which to base a conclusion. We found from our earlier double application study  that this does not necessarily constitute a significant problem for treatment because any lice hatching from eggs after a first treatment appear to be killed by a second treatment at 7 days. A treatment given at that time delivers more of the active material to any unhatched eggs, which further inhibits their chances of hatching. However, this information that eggs can take longer than one week to hatch emphasises the need for vigilance in confirming whether a treatment has been effective, by detection combing after completion of the treatment regimen, and also confirms the need for adequate application technique . So, just because more than 90% of people appear louse free 2 days after a second treatment it does not mean that further checks are not necessary as some viable eggs may remain.
Although numerous lice were eliminated using the 1% permethrin creme rinse at each of the treatment applications, more than 60% of participants received no respite from infestation and, of those who appeared louse free one or two days after treatment, fewer than half were cured of their infestation, even though we used more than twice the supposedly adequate application dose on each participant. Why then did we choose 1% permethrin as the comparator product rather than some alternative preparation? The reason 1% permethrin was used in this study was to provide data in comparison with a known medicinal product for those territories where such data are required by decision makers before issuing approvals. On this basis the number of possible comparators is extremely limited because most products have a limited geographic distribution. The only other insecticide active used widely is 0.5% malathion but this was not selected because the range of formulations used in different territories are not comparable even within themselves (shampoos, alcohol based lotions with or without terpenoids added, and water based emulsions). Additionally, the one product still listed in the UK was not available at the time the study was conducted.
The outcome using permethrin mirrors closely the findings of a previous investigation comparing treatments using this product with and without combing , and also reflects the outcome found in other studies. Given the number of investigations in which permethrin and other insecticide products have delivered an unacceptably low efficacy [3, 8–12], a review of the licensing of these preparations appears long overdue. It is understandable that sponsors may wish to use insecticide based products as comparators in clinical studies because they have a long history of use and are familiar to the decision makers within the various health services where the profile of new products needs to be raised. However, we have found that ethics review boards are increasingly reluctant to authorise their use in clinical investigations primarily because their efficacy is not much greater than using a placebo. Therefore, as long as these products retain a marketing authorisation, and the validity of this is not reviewed by the various competent authorities, consumers and prescribers will continue to use ineffective products. Consequently, now is probably the time for such a review to take place and for insecticide products to be removed from the market simply because so many treatments fail.