Breakthrough cancer pain: A delphi consensus study on expert recommendations for barriers that prevent the proper management of BTcP in Spain

Author(s): Yolanda Escobar Álvarez*, Javier Cassinello Espinosa, Joaquín Montalar Salcedo, Ramón de las Peñas, Fernando Caballero Martínez and Ana Blasco Cordellat Background: The management of Breakthrough cancer Pain (BTcP) remains unsatisfactory. Although many barriers to BTcP management have been identified, oncologists have not been able to overcome them. The aim of this study is to identify the barriers preventing proper BTcP management that Spanish medical oncologists have found, and to reach a consensus in order to draft ... Abstract View Full Article View DOI: 10.17352/ojpm.000020


Introduction
Breakthrough cancer Pain (BTcP) is commonly defi ned as the transient exacerbation of pain that occurs either spontaneously or in relation to a predictable or unpredictable trigger (an incident), despite stable, controlled background pain [1,2]. Currently, there is no universally accepted defi nition of BTcP [1,3]. This lack of worldwide agreement may make it diffi cult to adequately discriminate BTcP from uncontrolled background pain and lead to under diagnosis, despite the existence of diagnostic algorithms [1][2][3][4].
In less than 10% of all cases, the pain is not related to either the malignant disease or its treatment [6]. This variability complicates its diagnosis and treatment [4,5,7].
BTcP is a major indicator of poor clinical outcome and lower effi cacy of opioid treatment [4]. Moreover, it promotes functional deterioration and has a negative impact on Quality of Life (QoL) [5] and bears a signifi cant physical, psychological and economic burden [9]. Therefore, BTcP should be adequately identifi ed and treated (along with anti neoplastic treatment) to minimize the intensity and severity of the episodes and to lessen the impact on patients' QoL [1].
BTcP is still a little-known problem with serious consequences on patients' health; it is not well researched and may be incorrectly treated [8,11]. Various evidence suggests that it is often managed suboptimally [4]. Several barriers that prevent proper BTcP management have been identifi ed [1], which arise from healthcare professionals, patients themselves and healthcare settings [5]. Even so, diagnostic and therapeutic inertia makes it necessary to identify more barriers and fi nd solutions to eliminate the defi ciencies or problems detected in BTcP management.
The objectives of the BARDIO consensus were to explore and identify the main barriers preventing the correct management of BTcP in standard Spanish clinical practice, and to provide solutions to the highest-priority problems by developing recommendations.
For this purpose we used the Delphi method, an accepted methods available for attaining expert consensus [12]. It is a structured process that starts defi ning a problem, and then involve: developing questions for experts to resolve, selecting a panel of experts, using open-ended questionnaires, performing controlled assessment and feedback (qualitative and quantitative analysis), and follow-up (reassessment) using multiple rounds of surveys until a consensus is reached [12].

Materials and methods
This study was carried out through a survey of doctors' opinions (the Delphi method). The validity of the Delphi method is supported by the participation of a large number of experts who have knowledge and an interest in the topic and the use of successive rounds of the questionnaire [13,14]. This justify that it is one of the reasonably well accepted methods available for attaining expert consensus [12].
In Spain, this type of study is not among those that require the approval or written consent of Research Ethics Committees (RECs).
A scientifi c committee comprised of fi ve leading oncologists in this fi eld reviewed the objective of the study and developed an initial questionnaire concerning the main barriers of BTcP management (which were dependent on patients, physicians or healthcare professionals and health organizations).
Subsequently, a coordinating panel (made up of 23 oncology specialists selected by the scientifi c committee) reviewed and validated the questionnaire and proposed solutions to the barriers. The scientifi c committee then reviewed the results and comments and used them to develop a Delphi questionnaire, which would later be answered by an expert panel to reach a consensus on the proposed solutions. The scientifi c committee also selected the members of the expert panel (n=88 oncologists) using the snowball sample technique. This panel, stratifi ed among autonomous communities based on the group size in each territory, participated without remuneration.
A technical team was responsible for the method implementation (editing and dissemination of the questionnaires, analysis of responses and statistical interpretation of the consensus reached). The study design and all participants are shown in Figure 1.
Each questionnaire item was formulated as an assertion and assessed on a 9-point, single, ordinal, Likert-type scale: 1-3= disagree; 4-6= neither agree nor disagree; 7-9= agree. Individual observations and new proposals for consideration could be added.
We used the modifi ed Delphi method (a technique of professional consensus performed through written surveys) in two rounds [15]. The Delphi questionnaire (an online survey) had 41 items distributed in proposals for improvement on 1) patient-dependent barriers (9 items); 2) barriers dependent on the physician/healthcare personnel (22 items); and 3) barriers dependent on the health organization (10 items). The survey rounds were performed between May and June 2017.
The median score of each item was evaluated. Consensus was considered to be reached when at least two-thirds of the panel ranked the item within three points of the median: 1-3 Citation: Álvarez  points in the case of "disagreement" and 7-9 in the case of "agreement." Items with a median score located in the region of 4-6 were considered "indeterminate." When the scores of a third or more of the panelists were within the region of 1-3 and the scores of another third or more were within the region of 7-9, the item was considered "without consensus." After the fi rst Delphi round, panelists were informed of aggregate-level summary statistics of the individual responses (mean, median, percentage of distribution of the respondents situated outside the region of median) and the type of consensus reached. This summary also included any written comments made by panelists. The items without consensus, those with a high dispersion of opinions and those marked "indeterminate" were considered for reassessment in the second Delphi round.
The panelists then submitted a new individual assessment on these items.
After the second round, the results were analyzed according to the same criteria of the fi rst round. Items without consensus were analyzed descriptively in order to distinguish those that refl ected opinions that were markedly different between the panelists from those that fell within the "indeterminate" region.
The mean score of each item was also calculated, with a 95% Confi dence Interval (CI). The lower amplitude of CI is explained by greater unanimity of opinions in the group. A more extreme mean score indicated a more evident consensus in terms of agreement or disagreement.

Results
Of the 27 items included in the fi rst proposal of the questionnaire about the barriers preventing BTcP management, the coordinating panel reached consensus in six items ( Table   1); none of them in the block of patient-dependent barriers.
The consensus was in terms of "disagreement" in one item  In the remaining items (n=3 [6, 29 and 34], each in a different block; 7% of the total) there was no consensus due to disparity of professional opinion or lack of criteria (Table 2).  (Table 3).

Discussion
Although BTcP and its proper management have been widely researched, evidence shows that it is still managed suboptimally [4][5][6][16][17][18]. The aim of this study was to establish consensus on the barriers present in Spanish clinical practice for BTcP management, and to suggest recommendations to address them. The use of the Delphi technique allowed for the anonymous participation of a large number of experts distributed throughout Spain, thus avoiding the risk of some experts dominating responses, and without the time/ geographical restraints of other methods [19].  Among the barriers preventing BTcP control that were initially proposed by the scientifi c committee, those related to patients were met with the most doubt. It is known that patient assessment is poor in oncologist consultations [20]. It has been previously reported [23] and identifi ed as one of the reasons for the non-implementation of recommendations from clinical practice guidelines in Spain [24].
The other physician-related barrier that demonstrated agreement was the lack of adequate BTcP anamnesis, which is essential for BTcP diagnosis [7] and has been highlighted in previous Spanish consensus recommendations [25]. The integration of informatics should be promoted between primary and hospital care, as electronic prescription is an adequate tool for treatment control, drug interactions and patient comorbidities.  The effective inclusion of pain, both chronic and irruptive, as the fi fth vital sign in the assessment of oncological patients.

2
The development of training/informative programs for patients and their caregivers. Informational material in simple language including the defi nition, characteristics and treatment of BTcP may be part of these programs.

3
The creation of specifi c palliative medical consultations (either face-to-face or via phone) and quick outpatient consultations, in order to meet patients' needs and facilitate the understanding and management of BTcP. The extension of oncological consultation time could improve physicians' explanations and patients' understanding. Access to day hospital (both mornings and afternoons) to help control symptoms between scheduled visits to the oncologist.

4
The creation of specifi c oncology nursing consultations would improve the understanding, management and monitoring of cancer pain symptoms. Accurate written instructions could be used for pain management. In order to optimize the time for BTcP patient titration, continuous monitoring by a specialist nurse is recommended.

5
For symptom control, it must be emphasized that it is essential to train the physicians from the beginning of the oncologists' Internal Medical Residency Program. In order to achieve pain control, accurate and practical training/information sessions, together with hospital clinical sessions based on BTcP and promoted by the Medical Oncology service with the assistance of other specialized doctors, is recommended. It is essential to introduce the concept of pain as a critical cancer symptom

6
Provision of specifi c training on BTcP for nurses with expertise in oncology services.

7
To improve the training of healthcare professionals, it is necessary to increase the availability of guidelines with clinical recommendations for BTcP management (with schemes or algorithms facilitating the use of the treatments).

8
Recommended solutions for optimizing BTcP management: -A complete and organized interview in each visit, with specifi c and accrual pain anamnesis to avoid any confusion between poorly managed baseline pain and BTcP. A review of the medication should also be recorded.
-BTcP targeted anamnesis, using fast and simple tools (such as the Davies algorithm) to rule out its presence.
-The use of informational leafl ets and questionnaires prior to the consultation to facilitate systematic BTcP anamnesis.
-The use of patient diaries to adjust patients' titration (including rescue medication at times to reduce pain intensity).
-Specifi c questionnaires, visual scales and simple applications to allow healthcare professionals to interpret patient-reported information.
-The presence of caregivers during consultations in the case of cognitive impairment.

9
Frequent re-evaluation of the analgesic effect and drug toxicity of the medications received

13
Sensitization of the health administration to the consequences of the poor management of cancer symptoms, in order to increase the resources available between scheduled oncology consultations.
team involving many healthcare professionals (oncologists, pharmacists, nurses, etc.) in different clinical settings (inpatient-outpatient [ambulatory and primary care]). However, in this study the role of pharmacists was not mentioned, despite the fact that they can provide a broad scope of services that may be very useful for cancer pain management [26]. As stated by the panel, effective interactions between specialists are crucial for adequate pain management [26].
When the expert panel assessed the recommendations suggested by the scientifi c committee (using the Delphi questionnaire), a high degree of consensus was observed, always in terms of agreement. Only three recommendations did not reach consensus: one in the block of patient-dependent barriers (about the execution of educational campaigns for the general population), another in the block of physician/ healthcare personnel barriers (about problems related to the non-availability of all effective BTcP drugs in hospitals) and the last one in the block of health organization barriers (about the inappropriateness of remote titration of drugs for BTcP control).
The lack of consensus on the execution of educational campaigns for the general population may refl ect the questionable utility of these campaigns for cancer patients without pain or with multifactorial pain, despite the fact that pain management education has been shown to rectify patients' misconceptions of pain, reduce pain and improve QoL [5]. When the recommended educational/informative programs were meant for patients and caregivers, the degree of consensus was very low (with dispersed opinions). The diffi culty in carrying out this program, due to time and space constraints and a shortage of professionals available for sessions, could justify this result [5]. On the other hand, the However, nurses' understanding of BTcP is currently considered insuffi cient and, despite the existence of specifi c guidelines [27], more training is needed [28].
With respect to the second recommendation without consensus-the impact of the non-availability of all effective BTcP drugs in hospitals on residents' learning and patients' self-confi dence-it must be taken into account that there are different options and a wide variety of formulations [16,29], and that the new galenic preparations are considerably more expensive than existing alternatives [30]. The need for education on cancer pain management has been extensively reported in the past [31] and this need still persists [1]. Therefore, an early and specifi c BTcP education program could improve the situation. On the other hand, the fact that the patient was the main source of information for the BTcP assessment, coupled with the need to educate patients and relatives in order to maximize its control [4,5,29], refl ect the requirement of the patient's adequate cognitive functioning and the presence of a caregiver (when necessary). The high degree of consensus that was also reached on the need for accurate anamnesis and medication reassessment clearly demonstrates the panelists' knowledge of the relevance of information collection during consultations, and also the need to improve it. Better physician-patient communication and greater implementation of BTcP guidelines could address these needs, requiring more time and physician education [24].
The last recommendation without consensus was the inappropriateness of remote titration of drugs for BTcP control.
The suitability of telephone assessments for the titration of drugs for BTcP control (such as fentanyl) has already been described in the literature [32,33]. However, various aspects led to non-consensus, such as the availability of personnel to perform this task, the need to carefully select the appropriate The main strength of this study is the fact that it is based on responses (response rate: fi rst round 97.8%, second round 100%) from a national panel of experts. However, limitations must be recognized; there could be a disparity between the responses of the oncologists from the different Spanish autonomous communities, yet our fi ndings aim to be representative of the overall population. Additionally, it should be noted that the study has been addressed to oncologists; it could be appropriate to discuss this subject with other healthcare professionals (primary care services, palliative care units and other hospital teams).

Conclusions
Our results demonstrate that Spanish oncologists are aware of the main barriers for BTcP management. A strong consensus was reached on most of the proposed recommendations that were evaluated, refl ecting the oncologists' opinions of the convenience of BTcP management that is centralized in oncologist consultations. However, due to lack of time and training, oncologists consider more support (including trained personnel outside of the oncologist consultations, such as nurses, primary care physicians, etc.) and more resources to be necessary in order to improve BTcP control.