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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.106 no.6 Madrid jun. 2014




Treatment preferences of patients with Crohn's disease: Development of the IMPLICA questionnaire

Preferencias terapéuticas de los pacientes con enfermedad de Crohn: desarrollo del cuestionario IMPLICA



Natalia Borruel1, Javier Castro2, Sabino Riestra3, María Costi4 and Francesc Casellas1

1Unitat Atenció Crohn-Colitis. Hospital Universitari Vall d'Hebron. CiberEHD. Barcelona, Spain.
2Hospital Arquitecto Marcide. El Ferrol, A Coruña. Spain.
3Hospital Central. Oviedo, Asturias. Spain.
4AbbVie Farmaceutica, S.L.U. Madrid, Spain

Financial support: J. Castro received honoraria for consultancy from Abbott and MSD. President of EIGA (Asociacion Gallega de EII, nonprofit entity) which received grants for research from Abbott and MSD. S. Riestra participated in some Advisory Board of Abbott, MSD and Shire. Received grants for research from Abbott and MSD. M. Costi is employee of AbbVie Farmaceutica, S.L.U.





Introduction and objective: Patient preferences with respect to available therapies must be taken into account if the quality of care of patients with Crohn's disease is to be improved. The objective was to develop the IMPLICA preferences questionnaire for Crohn's disease patients treated with biological therapies.
Methods: As per standard methodology, the questionnaire was developed in Spanish language, in five stages: 1. Literature review to identify attributes related to biological therapies in Crohn's disease; 2. Expert meeting to identify attributes most relevant for patients; 3. Scoring of the most relevant attributes and generation of scenarios; 4. Patient comprehension test for selection and validation of scenarios; and 5. Final list of scenarios and qualitative evaluation of those most accepted by patients.
Results: Three attributes related to various characteristics of biological treatments were selected: route of administration, place/duration of administration and person administering the treatment; a combination of them produced seven possible scenarios. The comprehension test gave rise to significant modifications in the instructions, text of the scenarios and response categories.
Conclusion: IMPLICA is the first questionnaire to evaluate treatment preferences of Crohn's disease patients receiving biological therapies. This questionnaire facilitates patient's selection of the most appropriate real world treatment option and, therefore, it can be considered a useful tool when deciding the most appropriate and feasible treatment in normal clinical practice.

Key words: Crohn's disease. Preferences. Biological therapy.



Crohn's disease (CD) is a chronic gastrointestinal (GI) inflammatory disease that may affect any part of the digestive tract. The prevalence of CD in Spain is estimated to be 87.5 patients per 100,000 of the general population (1).

The introduction of anti-TNF biological therapies for the treatment of CD has significantly reduced the number of relapses, invasive tests and hospitalizations (2,3). CD causes an important deterioration in quality of life of patients (4) which may improve, even to a normal perceived health status, in the majority of patients treated with biological therapies (5). Short and long term beneficial effects of biological therapies, for CD patients suggest that their use will increase over time.

Aspects such as price and access to biological treatments do not currently impact CD patients in Spain. For this reason, and because of the similar efficacy and safety profiles of available biological treatments (7) it seems logical to seek patient's involvement in the choice of treatment. Various studies have shown that patients with CD wish to be actively involved in the decision making process (8,9), which is also related to better therapeutic adherence (10,11) and leads to more effective treatment and a consequent better control of the disease and improvement in quality of life.

Previous studies have assessed patient preferences with respect to the risk-benefit balance of treatments that can be determinant when making a treatment choice (12). The majority of those performed on patients with CD are based on the risk-benefit of treatments (13-15), while few are based on patient preferences related to the method or route of administration of a biological treatment (16).

Evaluation of preferences is performed by means of questionnaires that usually compare different types of treatment. "Conjoint analysis" is one of the techniques used to develop questionnaires and evaluate preferences in areas such as market investigations (17) or in healthcare (18,19), conjoint analysis is based on the preferences expressed by patients based on a defined set of options or therapeutic scenarios.

Since the use of biological therapies in the treatment of CD is becoming more common and more frequently patients are involved in deciding which biological treatment they are going to be treated with, it seems necessary to have a tool or questionnaire for the standardized evaluation of patient preferences with respect to biological therapies that will at the same time improve the quality of care of CD patients.

The aim of this qualitative research is to describe the development of the IMPLICA patient preferences questionnaire for CD patients treated with biological drugs.


Methods - development of the questionnaire

The IMPLICA (patient involvement in decision making in Crohn's disease) questionnaire for the evaluation of preferences for treatments of patients with CD. We would like to highlight that patients' participation in different phases was essential in IMPLICA questionnaire development. This questionnaire has been developed in Spanish language, and the development process included the five following phases:

1. Literature review and identification of attributes

A literature search and review was first performed to identify treatment characteristics that would be most relevant from the point of view of a CD patient. Based on this information, a list of attributes (characteristics) related to patient preferences, with respect to CD treatment, was prepared.

2. Expert meeting

A group of four CD experts with previous experience in patients preference studies reviewed the list and selected those attributes that, in their opinion, patients would find feasible and important. Each one of the experts rated the attributes from greatest to least importance. Also, the group assigned different levels/options to each of the selected attributes. Furthermore, it was agreed that the IMPLICA questionnaire should be based on real treatment options. An assumption of equivalence of efficacy and safety of biological treatments was made, based on the European evidence-based Consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease of the European Crohn's and Colitis Organization (ECCO) guidelines (6).

3. Scoring of attributes and generation of scenarios

Based on the work of the experts, the various attributes and levels were combined to prepare an initial group of scenarios. Scenarios that did not reflect a real situation were eliminated, as consensually recommended by the experts.

Using the resultant group of scenarios, the attributes related to biological treatments that would be most useful or important to patients when making decisions on the choice of treatment for CD were selected. This was achieved by using the scores assigned to each attribute/characteristic in the expert meeting. The resultant scenarios were used to prepare the first version of the IMPLICA questionnaire.

4. Selection and validation of scenarios

Using the selected scenarios, linguistic comprehension of the questionnaire was assessed by administering it to a group of five CD patients treated with biological therapies, without particular disease severity.

For each scenario, patients had to answer questions related to wording of the questionnaire's instructions, to the scenarios, and to the response options. As a result, the second version of the IMPLICA questionnaire was produced.

5. Final wording of the questionnaire

Because the redaction of the scenarios and response categories had changed in a significant manner, it was decided that a modified IMPLICA questionnaire (version 2) should be administered to a group of 20 patients to test its comprehension and a final version of the questionnaire was prepared. In addition, a quantitative evaluation of the scenarios that were most accepted by patients was performed.



A MEDLINE search (limited to publications from the previous 10 years) was performed with the following descriptors: Patient* AND preferences AND (IBD OR "inflammatory bowel" OR CROH* OR "ulcerative colitis"). The search resulted in 51 articles, of which 31 were eliminated (not evaluating patient's treatment preferences or not related to any type of inflammatory bowel disease. The attributes identified by the search were: Mode of administration, time free of symptoms/disease control, symptoms/disease control, non-serious adverse events, serious adverse events and long term serious adverse events.

The expert meeting resulted in six attributes: Route of administration, administration site and total administration time, person administering treatment, treatment adverse events (local), product source (human, animal) and time the drug has been on the market. The levels and categories shown in table I were agreed for every attribute in the same meeting.



Combining these factors produced a total of 144 scenarios, two attributes with three levels and four attributes with two levels. The total number of scenarios can be calculated as follows: 32x24 = 144. Scenarios or situations that could not occur in real treatment were excluded, leaving 22 possible scenarios.

Of these 22 scenarios, it was observed that the attributes "adverse events", "product source", and "time on market" were directly related to the route of administration (for example, intravenous administration is associated with infusion reactions, while subcutaneous administration is associated with local reactions). Therefore, there was no reason to maintain these three attributes; the selection of one scenario or the other within a route of administration will always be associated with one of these three constant attributes. Thus, 18 possible scenarios were identified, with three variable attributes; route of administration, administration site and person who administers the treatment.

Of these 18 scenarios, those that were logically impossible or that could not occur in a real-life situation were eliminated, producing the final seven scenarios that are presented in table II. Because these seven scenarios were considered feasible, it was not necessary to undertake a fractional factorial procedure (SPSS orthoplan) (20); a technique used when the number of scenarios is much greater.



The first version of the IMPLICA questionnaire (Fig. 1) was prepared using the seven scenarios; it was then administered to a group of five CD patients for a comprehension test.



Changes were made to the instructions, scenarios and response options based on the results of the comprehension test. Changes were considered relevant when at least two patients suggested changes to the text. In summary, the instructions section was abbreviated, the text of the scenarios was reduced to make it more direct (for example, "Treatment administered by intravenous route" was changed to "Type of injection: INTRAVENOUS") and, the response options were changed from a 0 to 9 to a 0 to 4 scale (never to always) because two of the patients found it easier to score on a reduced scale. The format of the response categories was also changed. These changes were included in version 2 of the IMPLICA questionnaire (Fig. 2).



The administration of version 2 of the IMPLICA questionnaire to 20 CD patients did not result in additional changes, neither in the content nor in the format of the questionnaire. The 90 % of the CD patients answered all scenarios included in the IMPLICA questionnaire.

Scenario "F" (subcutaneous treatment, self-administration and in patient's home in less than 30 minutes) (Fig. 3) was selected "always" or "almost always" by 80.0 % of the 20 patients. The next best rated scenarios were "G" and "E" (50.0 % and 40.0 %, respectively rated them "always" or "almost always"). These three scenarios included subcutaneous treatment, and administration in the patient's home. The least selected scenario was "C", with 77.8 % of patients rating it "never" or "almost never", followed by options "A" and "D", with 66.6 % and 65 %, respectively. None of the least rated scenarios included home-administration.



None scenario obtained minimum overall scores (all patients answered "never") or maximum (all patients answered "always"), in other words, there are not any scenarios of IMPLICA questionnaire that have floor effect or ceiling effect.

In terms of value or scoring of the importance of attributes, it was observed that the factor "person administering treatment" had greatest influence over the selection of scenarios (importance 49.6 %), followed by "administration site of the treatment" and "route of administration", with 36.3 % and 14.1 %, respectively.

The attribute "site of administration of treatment" was selected as being most important or second most important by 84.2 % of patients when selecting scenarios in the section in which they had to place in order the three attributes of the IMPLICA questionnaire in order of importance.

Once the development phase of the IMPLICA questionnaire had been completed, the final questionnaire contained seven scenarios. Each of the scenarios had three attributes; route of administration, person administering treatment and administration site. The attribute administration site also included administration time but patients stated that it would be preferable to separate administration site from duration, as patients said there was quite information in one sentence. The English version was translated literally into Spanish and not validated in English population.



The IMPLICA is the first questionnaire for the evaluation of CD patient's preferences on biological treatments under real options of treatment.

There are many benefits, both for the patient and the healthcare professional, associated with involvement of the patient in treatment related decisions. Such an improvement in communication increases patient's satisfaction with quality of care and treatment adherence (21). It has been observed in oncology patients that the relation between communication and therapeutic adherence helps patients to better psychologically adapt to their illness (22).

It is important that CD patients are informed of the characteristics of each possible therapeutic option and understand the associated risks and benefits (23). For this reason, it is necessary that all messages and information are clear, so that each patient can make the best possible informed decision.

The IMPLICA questionnaire may improve the quality of treatment of CD patients, allowing them to choose the treatment that best matches their needs, based on the information provided in a standardized way. This questionnaire could be of great help to healthcare professionals allowing them to involve patients in a standard clinical setting in the decision making process in a simple, rapid and easy to use fashion.

The difference between the IMPLICA questionnaire and others assessing preferences of CD patients is that in the majority of studies, treatment risk-benefit is evaluated; with the patient being informed of medium and long term serious adverse reactions, up to and including death (24). To this end, the IMPLICA questionnaire is different despite using a similar methodology for its development. It includes attributes that impact directly, from the first use of the drug, on the day to day life of the patient on aspects as important as work or family life.

Preliminary results of the IMPLICA questionnaire indicate that the scenario most preferred by patients was "F", subcutaneous, home-based, auto-administration. However, since these are purely descriptive data obtained from a small sample of patients, it cannot be concluded that this would be the scenario preferred by the majority of CD patients starting on biological treatment.

The IMPLICA questionnaire development study has the following limitations; firstly, unlike other studies, no question was included to evaluate reasons for selecting scenarios. Nonetheless, the final question asks which of the three attributes has the greatest influence on the decision, thus providing the clinician with sufficient information on the patient's preferences and the treatment characteristics on which the decision was based. The second limitation was that no patients were included in the expert meeting group, thus missing the inclusion of potential additional attributes to the questionnaire; however, this limitation was minimized by the participation of patients in the comprehension test phase. Another limitation is that previous patient experience with biological treatments was not taken into account, nor was the severity of the disease or the number of years from diagnosis in the comprehension validation test. A large sample allow stratification of the sample, by biological treatment type and other clinical variables would have yielded more information and allowed knowing up to what point choice of scenarios was related to previous treatments or CD severity.

These aspects will be analyzed in further work, with a larger sample of CD patients naïve to treatment with biologics, which will allow us to establish the preferences and utilities of patients by means of a "conjoint analysis". In this first phase, it was possible to build a questionnaire that meets the requirement that the number of attributes is not greater than seven (25). Further research is needed to assess the relation between the different sociodemographic and clinical patient characteristics and selection of scenarios in the IMPLICA questionnaire, and the relationship between information received by the patient and preferences found when the IMPLICA questionnaire is administered.



1. Saro C, Riestra Menéndez S, Milla Crespo A, Sánchez Fernández R, Lacort Fernández M, Argüelles Fernández G, et al. Incidencia y prevalencia en enfermedad inflamatoria intestinal crónica. Estudio asturiano en cinco áreas. An Med Interna 2003;20:3-9.         [ Links ]

2. Faegan BG, Panaccione R, Sandborn WJ, D'Haens GR, Schereiber S, Rutgeerts PJ, et al. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology 2008;135:1493-9.         [ Links ]

3. Taxonera C, Rodrigo L, Casellas F, Calvet X, Gómez-Camacho F, Ginard D, et al. Infliximab maintenance therapy is associated with decreases in direct resource use in patients with luminal or fistulizing Crohn's disease. J Clin Gastroenterol 2009;43:950-6.         [ Links ]

4. Casellas F, Arenas JI, Baudet JS, Fabregas S, Garcia N, Gelabert J, et al. Impairment of health-related quality of life in patients with inflammatory bowel disease: A Spanish multicenter study. Inflamm Bowel Dis 2005;11:488-96.         [ Links ]

5. Casellas F, Robles V, Borruel N, Torrejón A, Castells I, Navarro E, et al. Restoration of quality of life of patiens with inflammatory bowel disease after one year with antiTNFalpha treatment. J Crohn's Colitis 2012;6:881-6.         [ Links ]

6. Travis S, Van Assche G, Diagnass A, Cabré E, Gassull MA. On the second ECCO consensus on Crohn's disease. J Crohns Colitis 2010;4:1-6.         [ Links ]

7. Esser D, Cornillie F, Diamond RH, Spiegel RJ. On the updated ECCO consensus guidelines for medical management of Crohn's disease. J Crohns Colitis 2011;5:165-6.         [ Links ]

8. Bears JE, Markus T, Kuipers EJ, van der Woude CJ. Patients' preferences regarding shared decision-making in the treatment of inflammatory bowel disease: Results from a patient empowerment study. Digestion 2010;81:113-9.         [ Links ]

9. Siegel CA. Making therapeutic decisions in inflammatory bowel disease: The role of patients. Curr Opin Gastroenterol 2009;25: 334-8.         [ Links ]

10. Barton JL. Patient preferences and satisfaction in the treatment of rheumatoid arthritis with biologic therapy. Patient Prefer Adherence 2009;3:335-44.         [ Links ]

11. Duarte JW, Bolge SC, Sen SS. An evaluation of patients' preferences for osteoporosis medications and their attributes: The PREFER-International study. Clin Ther 2007;29:488-503.         [ Links ]

12. Plantinga LC, Fink NE, Bass EB, Boulware LE, Meyer KB, Powe NR. Preferences for current health and their association with outcomes in patients with kidney disease. Med Care 2007;45:230-7.         [ Links ]

13. Van Houtven G, Johnson FR, Kilambi V, Hauber AB. Eliciting benefit-risk preferences and probability-weighted utility using choice-format conjoint analysis. Med Decis Making 2011;31:469-80.         [ Links ]

14. Siegel CA. Lost in translation: helping patients understand the risks of inflammatory bowel disease therapy. Inflamm Bowel Dis 2010;16:2168-72.         [ Links ]

15. Johnson FR, Hauber B, Özdemir S, Siegel CA, Hass S, Sands BE. Are gastroenterologists less tolerant of treatment risks than patients? Benefit-risk preferences in Crohn's disease management. J Manag Care Pharm 2010;16:616-28.         [ Links ]

16. Allen PB, Lindsay H, Tham TC. How do patients with inflammatory bowel disease want their biological therapy administered? BMC Gastroenterol 2010;10:1.         [ Links ]

17. Green PE and Srinivasan V. Conjoint Analysis in Marketing: New Developments with Implications for Research and Practice. J Marketing 1990;54:3-19.         [ Links ]

18. Ryan M, Farrar S. Using conjoint analysis to elicit preferences for health care. BMJ 2000;320:1530-3.         [ Links ]

19. Bridges J, Kinter E, Kidane L, Heinzen RR, McCormick C. Things are looking up since we started listening to patients. Trends in the application of conjoint analysis in health 1982-2007. Patient. 2008; 1(4):273-82.         [ Links ]

20. Home page on the Internet.         [ Links ]

21. Sánchez N, Salamero M, Sirgo A, Hollenstein MF, León C, Lacorte TM. Preferencias de comunicación y apoyo de pacientes oncológicos españoles. Adaptación del "measure of patient's preferences". Psicooncología 2005;2:81-90.         [ Links ]

22. Zachariae R, Pedersen CG, Jensen AB, Ehrnrooth E, Rossen PB, von der Maase H. Association of perceived physician communication style with patient satisfaction, distress, cancer-related self-efficacy, and perceived control over the disease. Br J Cancer 2003; 88:658-65.         [ Links ]

23. Deber RB. Shared decision making in the real world. J Gen Intern Med 1996;11:377-8.         [ Links ]

24. Van Houtven G, Johson FR, Kilabmi V, Hauber AB. Eliciting benefit-risk preferences and probability weighted utility using choice-format conjoint analysis. Med Decis Making 2011;31:469-80.         [ Links ]

25. Ryan M. A role for conjoint analysis in technology assessment in health care? Int J Technol Assess Health Care 1999;15:443-57.         [ Links ]



Natalia Borruel.
Digestive System Research Unit.
University Hospital Vall d'Hebron.
Passeig de la Vall d'Hebron, 119-129.
08035 Barcelona, Spain

Received: 21-05-2013
Accepted: 10-07-2013

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