On 2018 Jan 05, Mogens Groenvold commented:

Thank you very much to the Cicely Saunders Institute Journal Club and Javiera Leniz Martelli and Katherine Bristowe for an insightful discussion of key aspects of our article.

Concerning ‘standard care’ in the control group we are currently analyzing and comparing the health care activities in the two groups. This will map the palliative care activities offered outside SPC and clarify whether there was ‘compensation’ in the control group.

Regarding the primary outcome, the most important point to make is that while we did indeed devise and employ a new approach aimed at addressing the issue of heterogeneity in palliative care needs (Johnsen AT, 2013 p. 5 and Johnsen AT, 2014 p. 7), we also carried out a fully conventional analysis. The comparison of these two methods suggested that the new approach was slightly superior (Groenvold M, 2017 p. 822).

In the conventional analysis we compared the change over time between groups according to each of the seven EORTC QLQ-C30 scales selected by our clinicians as the key targets of their SPC. Some of the previous trials found an impact on generic health-related quality of life scales, and we have no reason to believe that our measures are less sensitive (unless our clinicians picked the ‘wrong’ scales; this will be elucidated in a forthcoming analysis of explorative outcomes). Therefore, unfortunately, we do not believe that positive effects have been attenuated in our analysis of the primary outcome.

In relation to the patient sample we agree that just as we sought to minimize heterogeneity in palliative care needs, the heterogeneity in cancer diagnoses should be minimized if the main concern is observe maximal effects on specific problems. However, we aimed at evaluating the impact of SPC in a mixed population of cancer patients with different needs, and, as suggested, a larger sample size may be required for this.

Finally, we agree that the possible lack of uniformity of the intervention between the six SPC units may have weakened the ability to detect a positive effect. Future analyses will elucidate whether the interventions differed between the units.

At this point in time we believe that the two most important explanations of the negative (or, in fact, neutral) trial outcome are that the SPC units may not have had an active, structured approach to early SPC, and that the eight-week trial period was too short. The ongoing analyses are likely to give additional insights.

On 2017 Dec 19, Cicely Saunders Institute Journal Club commented:

This paper was discussed at the Cicely Saunders Institute Journal Club on Wednesday 6th December. We appreciated the opportunity to discuss a well conducted RCT and to see it published even after getting a negative result. We enjoyed discussing this paper and it generated a series of reflections on the methods, in particular regarding the primary outcome.

We positively highlighted the detailed discussion about previous trials regarding early specialist palliative care (SPC) in the introduction, and the clear description of the randomization process as well as the blindness of analysts and the sensitivity analysis. We felt more information about what ‘standard care’ involved for individuals in the control group would have been beneficial.

We discussed extensively the use of patient’s primary need based on the EORTC QLQ-C30 dimensions as primary outcome. We agree with the authors about the importance of addressing the heterogeneity in palliative care patients needs and we value the use of measurements that are important for patients. We wondered if the nature of the outcome chosen required a larger sample size to show a difference between arms. It is clear that some of the dimensions would be easier to modify by a SPC team than others. That makes the positive effect SPC might have had in some dimensions being attenuated in the weighted mean. In addition, SPC might have a different impact according to type of cancer. Including all type of cancer patients increases the variability of the effect, and might require a larger sample size. We wondered if the lack of uniformity of the intervention among the different centres also contributed to lack of significant difference in the primary outcome.

Finally, we valued the discussion of the possible reasons for the lack of effect of the intervention, which need to be taken into account for future trials.

Commentary by Javiera Leniz Martelli and Katherine Bristowe

On 2017 Dec 19, Cicely Saunders Institute Journal Club commented:

This paper was discussed at the Cicely Saunders Institute Journal Club on Wednesday 6th December. We appreciated the opportunity to discuss a well conducted RCT and to see it published even after getting a negative result. We enjoyed discussing this paper and it generated a series of reflections on the methods, in particular regarding the primary outcome.

We positively highlighted the detailed discussion about previous trials regarding early specialist palliative care (SPC) in the introduction, and the clear description of the randomization process as well as the blindness of analysts and the sensitivity analysis. We felt more information about what ‘standard care’ involved for individuals in the control group would have been beneficial.

We discussed extensively the use of patient’s primary need based on the EORTC QLQ-C30 dimensions as primary outcome. We agree with the authors about the importance of addressing the heterogeneity in palliative care patients needs and we value the use of measurements that are important for patients. We wondered if the nature of the outcome chosen required a larger sample size to show a difference between arms. It is clear that some of the dimensions would be easier to modify by a SPC team than others. That makes the positive effect SPC might have had in some dimensions being attenuated in the weighted mean. In addition, SPC might have a different impact according to type of cancer. Including all type of cancer patients increases the variability of the effect, and might require a larger sample size. We wondered if the lack of uniformity of the intervention among the different centres also contributed to lack of significant difference in the primary outcome.

Finally, we valued the discussion of the possible reasons for the lack of effect of the intervention, which need to be taken into account for future trials.

Commentary by Javiera Leniz Martelli and Katherine Bristowe

On 2018 Jan 05, Mogens Groenvold commented:

Thank you very much to the Cicely Saunders Institute Journal Club and Javiera Leniz Martelli and Katherine Bristowe for an insightful discussion of key aspects of our article.

Concerning ‘standard care’ in the control group we are currently analyzing and comparing the health care activities in the two groups. This will map the palliative care activities offered outside SPC and clarify whether there was ‘compensation’ in the control group.

Regarding the primary outcome, the most important point to make is that while we did indeed devise and employ a new approach aimed at addressing the issue of heterogeneity in palliative care needs (Johnsen AT, 2013 p. 5 and Johnsen AT, 2014 p. 7), we also carried out a fully conventional analysis. The comparison of these two methods suggested that the new approach was slightly superior (Groenvold M, 2017 p. 822).

In the conventional analysis we compared the change over time between groups according to each of the seven EORTC QLQ-C30 scales selected by our clinicians as the key targets of their SPC. Some of the previous trials found an impact on generic health-related quality of life scales, and we have no reason to believe that our measures are less sensitive (unless our clinicians picked the ‘wrong’ scales; this will be elucidated in a forthcoming analysis of explorative outcomes). Therefore, unfortunately, we do not believe that positive effects have been attenuated in our analysis of the primary outcome.

In relation to the patient sample we agree that just as we sought to minimize heterogeneity in palliative care needs, the heterogeneity in cancer diagnoses should be minimized if the main concern is observe maximal effects on specific problems. However, we aimed at evaluating the impact of SPC in a mixed population of cancer patients with different needs, and, as suggested, a larger sample size may be required for this.

Finally, we agree that the possible lack of uniformity of the intervention between the six SPC units may have weakened the ability to detect a positive effect. Future analyses will elucidate whether the interventions differed between the units.

At this point in time we believe that the two most important explanations of the negative (or, in fact, neutral) trial outcome are that the SPC units may not have had an active, structured approach to early SPC, and that the eight-week trial period was too short. The ongoing analyses are likely to give additional insights.