Tailored intervention focussed on Self-Management and Acceptance to improve adherence in Severe Haemophilia (SMASH-study)

Since 1965, the introduction of intravenous clotting factor replacement therapy
has enabled the substitution of the missing clotting factor in haemophilia.
This therapy has been administered to treat bleeds (on demand) or as regular
replacement therapy (prophylaxis) to prevent bleeds3. Two aspects of treatment
make it especially demanding: the fact that treatment is intravenous, and the
short half-life of 12 hours of Factor VIII requiring frequent infusions
(usually 3 per week or every other day) to maintain though levels needed for
bleed prevention.

For effective prevention of bleeding, high adherence to treatment is crucial.
Recent studies on adherence and its determinants in 250 Dutch patients showed
that the non-adherence rate is 50% in adults (due to changing infusion time and
skipping doses)4. This is potentially very harmful, as even a single bleed can
lead to irreversible damage, especially in a joint or the central nervous
system. Inadequate treatment of a bleeding episode (starting too late or the
initial dose too low) leads to more damage5, more pain and prolonged treatment.
To prevent bleeding, prophylaxis should be continued without interruption. It
has been recently established that young adults who discontinued prophylaxis
for shorter or longer periods had significant more arthropathy after 10 years
of follow up than patients who continued prophylaxis5. Arthropathy leads to a
significant reduction of quality of life and labour force participation6,7 with
substantial societal impact. Moreover non-adherence dramatically reduces the
cost-effectiveness of prophylactic replacement therapy5. Treatment costs are
covered for >93% by the cost of the medication (mean ¤0.83 per IU1,8), and
therefore an more adequate treatment of even a single bleed is worthwhile.
Immediate treatment during a bleed is essential for efficient clotting factor
use. If an adult with severe haemophilia A has a joint bleed and starts at the
first signs of bleeding, a single dose of clotting factor concentrate (e.g.
2000IU) is sufficient. If he waits for 12 hours, the bleed has turned into a
major bleed, requiring 5 days of treatment with in total 10000 IU (including
additional visits to the clinic, physiotherapist and days lost from work).

Based on a systematic literature review9 and qualitative research10 lack of
self-management skills (in ± 25% of the total population) or acceptance
problems (also ± in 25%) were identified as the main reasons for non-adherence.
Patients with self-management problems failed to administer prophylaxis, due to
inadequate routine, forgetfulness and the complexity of the necessary
self-management skills. Bleeding occurred quite often in this group and
following the proper dosing schedules for treatment of a bleed was difficult
too. Patients with acceptance problems mostly administered concentrate
inadequately (e.g. only to treat bleeds, or dosing once weekly) and were at
risk for serious bleeding (joint or brain).

For improving disease acceptance, Acceptance and Commitment therapy,
(successful in patients with diabetes, HIV and chronic pain12,13) was adapted
for haemophilia patients. The aim for this study is to evaluate the effect of a
tailored intervention focused on disease acceptance for patients with
haemophilia on prophylaxis.

To evaluate the effects of a tailored invention focused on disease acceptance
for patients with haemophilia on prophylaxis.

Secondary objectives:
* Evaluation of feasibility of collection of preliminary outcomes:
o Adherence, measured with the Delphi definition, based on missing, dose
changing and timing changes;
o Annual number of bleeds;
o Direct medical costs and costs from a societal perspective.

Prospective observational pre post study, design shown in Figure 1. This
includes a group training programme focussed on illness acceptance.
Measurements will be administered before the training, data on disease specific
outcomes collected retrospectively (over one year). Furthermore, data will be
collected at T0, T2, T6 and a follow-up at T12.

Acceptance intervention (Dutch: Leven met hemofilie)
* 8 group sessions (7 sessions, 1 follow-up session) based on Acceptance and
Commitment therapy, guided by a specially trained haemophilia health care
provider;
* Focused on acceptance of haemophilia and prophylaxis;
* Each session will require 2 hours.

The risk of participating in this study is considered negligible; the
interventions are focussed on increasing haemophilia acceptance. Participants
may experience burden of dealing with emotions concerning their illness or by
the time investment, yet harm caused by the intervention is nearly impossible.
Patients may experience more self-confidence with haemophilia through increased
acceptance. Improved management of prophylaxis is expected to result in
improved prevention and bleeding control.