Protocol Assignment Forum: Clustering, Time Series

Sara Moassesfar
Protocol

May 7, 2015

Assignment 1:

1. What evidence are you proposing to translate into practice?

I propose to develop a protocol for the gradual weaning of glucocorticoids (steroids) in oncological patients who have been on steroids for longer than 10 days, and then retesting their hypothalamic-pituitary-adrenal axis with an ACTH stimulation test, in order to prevent undiagnosed and untreated adrenal insufficiency in patients.

A. Justify that this evidence is “ready for translation.”

There is an abundance of evidence in the literature from the past 40 years that adrenal suppression can occur when a patient is on high-dose steroids for more than 10-14 days (i.e. our usual doses of prednisone given in conjunction with chemotherapy for oncological conditions such as tumors or leukemia).  This adrenal suppression means there is less or no signaling from the hypothalamus to the pituitary gland, and then from the pituitary gland to the adrenal gland, to stimulate the adrenal gland to produce cortisol.  This results in low serum levels of cortisol, which can be dangerous to the patient.  Cortisol is a critical hormone that is necessary to maintain normal blood pressure, normal blood sugars and a normal sense of energy.  Those with deficiencies in cortisol are at risk for severe drops in blood pressure, blood sugars and even coma/death, particularly at times of stress, such as with a severe illness. As a result, pediatric endocrinologists have long been advising steroid replacement for those with cortisol deficiency, usually with hydrocortisone.  The need for steroid replacement is more obvious in patients with adrenal gland diseases that clearly don’t have functioning glands.  However, when pediatric patients are placed on high-dose steroids for 10 days or longer for treatment of another condition, such as cancer, sometimes their providers don’t consider that the hypothalamic-pituitary-adrenal (HPA) axis could be suppressed by this and do not provide a gradual weaning of the steroid so to reawaken the HPA axis.  Nor do they retest the axis with an ACTH stimulation test after topping the steroid, to ensure the axis is intact and the adrenal gland is capable of secreting normal levels of cortisol.  This puts patients at severe risk, particularly those who are already ill with cancer or other serious illnesses (1-5).  I have performed an extensive literature search and have not been able to find data yet on which percentage of pediatric oncology patients are discontinued abruptly from steroids and which percentage of these go onto have adrenal problems that come to medical attention.  This would be very useful data to have but I am not certain it is available in the literature; I will continue searching.

As endocrinologist, when we are consulted for pediatric oncology patients who have received high-dose steroids for prolonged periods of time, we make such recommendations and monitor.  However, we have noticed that we are often not consulted on such a patient and the oncology team may discontinue the steroid without these considerations, which again, can be detrimental to the patient. Thus, I am interested in putting a protocol into place to translate the abundant  evidence in the literature into actual practice and ensure every oncological patient in who receives a prolonged course of steroids (>10 days) in conjunction with their chemotherapy, eventually undergoes a standardized weaning of the steroid and formal retesting of the HPA axis.  There is a lot of evidence in the literature that this would be the best standard of care.

B. Identify a single, key behavior change target for your translational activity.

I would like to increase awareness and acceptance amongst pediatric oncologists of the dangers of abrupt discontinuation of a prolonged steroid course (that is >10 days) and have them follow guidelines for gradual tapering of the steroids and retesting of the HPA axis to ensure its normalization, before the discontinuation of the steroids.

2. Conduct a “gap analysis” of your target behavior.  Look to diverse sources for “best guess” estimates if specific measures are not available.

A.  What is the quality (performance) gap?

Currently, in practice, we often see that pediatric oncologists discontinue steroids abruptly after a prolonged course without consulting endocrinology, and without gradually tapering the dose and retesting the HPA axis with an ACTH stimulation test.  When we look at their protocols for the doses of prednisone given with chemotherapy, we see there are no guidelines for how to eventually taper off the medication and perform follow up lab evaluation.  Each oncologist seems to have different practices in this regards and there is no standardization. 

It is unclear why this gap exists; it may because some oncologists and nurse practitioners on their team are not aware of the evidence of the dangers of abruptly stopping steroids and would benefit from education on the topic.  It may be that the oncologists, nurses and nurse practitioners on their team do not feel they have adequate time to address these issues in clinic follow ups, in which case, we can have our endocrine team involved earlier and spend more time on these issues, in partnership with the oncology team. 

B.  What is the outcome gap?

With this protocol, we hope to close this gap and put a standard process in place, to be followed by each pediatric oncologist.  Our goal is this will lead to gradual tapering of the medication with each and every patient in this situation, and retesting with an ACTH stimulation test when appropriate.

3. Is there evidence that changing performance will improve health (clinical outcomes)?

There is a lot of evidence from previous cohort studies and reviews that shows that adrenal insufficiency can happen from an abrupt discontinuation after a prolonged course of steroids and that some of these patients can become ill with severely low blood pressure and hypoglycemia, often requiring rehospitalization (1-5).  Changing our approach to these patients will prevent these detrimental consequences and will improve health outcomes.

References

1. Maartje S Gordijn, Reinoud JBJ Gemke, Elvira C van Dalen, Joost Rotteveel, Gertjan JL Kaspers.  Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia.  Cochrane Library. Published Online May 16, 2012.
2. Stefan R. Bornstein. Predisposing Factors for Adrenal Insufficiency. N Engl J Med 2009; 360:22. 
3. R Schlaghecke, E Kornely, et al. The effect of long-term glucocorticoid therapy on pituitary–adrenal responses to exogenous corticotropin-releasing hormone. New England Journal of Medicine. January 23, 1992; 326:4.
4. James C. Melby. Drug Spotlight Program: Systemic Corticosteroid Therapy: Pharmacology and Endocrinologic Considerations.  Ann Intern Med.1974; 81(4):505-512. 
5. Briana C. Patterson, Karen Wasilewski-Masker, A. Blythe Ryerson, Ann Mertens, Lillian Meacham.  Endocrine Health Problems Detected in 519 Patients Evaluated in a Pediatric Cancer Survivor Program.  The Journal of Clinical Endocrinology & Metabolism.  Volume: 97 Issue: 3.  Published online Dec 21, 2011.

Assignment 2:

1  Define the community/communities for your project and explain why each is a stakeholder for your study.

The community we will be targeting is the pediatric oncologists.  They are stakeholders in this because they are looking out for the best interest of their patients and want to optimize their health.

We can also reach out to the parents and family members of these patients, as they are also important stakeholders and want the best level of care for their children.

2.  Describe your plan for approaching potential community partners to ask for their involvement.

We will want to extend our protocol to other clinics and health centers outside of UCSF.  We can do this by discussing our approach and its benefits with the Oakland clinic, Kaiser clinics and other clinics around us.

3.  Identify which stages of your project you'll incorporate community input, and describe what types of input you'll solicit.

First, I would like to get community input as to why there is not currently a protocol in place for weaning and stopping steroids and retesting the HPA axis. As I mentioned before, it is unclear why this gap exists. It may because some oncologists, nurses, and nurse practitioners are not aware of the evidence of the dangers of abruptly stopping steroids and would benefit from education on the topic.  It may be that the oncologists or nurse practitioners on their team do not feel they have adequate time to address these issues in clinic follow ups, in which case, we can have our endocrine team involved earlier and spend more time on these issues, in partnership with the oncology team.  To better understand what these barriers are, I plan to create a survey targeted at the oncology team to ask about why they do not follow a standard protocol for tapering and stopping steroids.  That way, we can try to address those barriers before designing and implementing our protocol (i.e. provide more education on the topic to the oncology team or offer endocrine consults early to make sure the issue is addressed).  We can develop this as a QI project at UCSF.  This may help generate more interest and engagement.

Once we identify the barriers and create an appropriate protocol, I would like to test the protocol at our own clinic at UCSF and gather more data on what works well and what doesn’t.  After we make appropriate revisions based on this data, then I would like to implement it into the management at other clinics.  At that point, I would like the other clinics to try the protocol and again gather data on what works well and what doesn’t, and give us that feedback so we can improve upon it.  The end goal would be to ensure proper gradual tapering of the steroids and retesting with an ACTH stimulation test, so it would be important to see if the protocol aids in doing this after a period of time, such as 6 months to 1 year. 

 3.  Name three ways you plan to share your results, beyond writing an academic article or presenting at an academic conference.

We can share them on our clinic website; this way, we will give access to a wider audience including the patients’ parents, primary care physicians and oncologists.

We can share them on other professional websites, such as that of the American Cancer Society.

We can create a pamphlet that details our protocol and the findings, to send to other clinics and health centers.  This pamphlet an also be distributed to support groups that parents and family members participate in, to get them more engaged too.

Assignment 3:

 1. Describe the organizational and/or delivery system environment in which your intervention will take place.

My protocol will first be implemented within the UCSF pediatric oncology clinic.

2. Based on Shortell’s 4 domains of organizational change, identify organizational barriers that could potentially impede successful implementation of your proposed intervention.

Environment: One possible barrier to my intervention may be that the oncology team’s schedule is so full and does not allow for extra time to address adrenal issues.  This may be one reason why they overlook this issue, even when they have some awareness of it.

Resource acquisition: Implementation of my protocol requires that physicians, nurses and nurse practitioners dedicate some of their clinical time to this protocol, which will require that they be financially compensated for their extra time.

Resource deployment: In the past, I have found some of our oncologists and oncology nurse practitioners have not been aware of the evidence for adrenal suppression with prolonged use of steroids and the risk of adrenal crisis. And once our endocrinology team consulted and provided this education, they were all on board with our recommendations and guidelines.  I suspect this is still the case with some members of their team.  

Quality-centered care:  Patients and their families spend a great deal of time in clinic follow-ups after hospitalizations as it is.  They likely will not be too pleased to spend an extra 20-30 min discussing adrenal issues at these sessions and recommendations for treatment.  The ACTH stim test itself can take up to 2 hours (considering time spent waiting in clinic), which is also not pleasant and may serve as a barrier.  This may serve as a barrier to proper care in some way, although I think most families will be willing to spend this extra time if they know it will be best for their child’s health.

3. Using the same 4 domain model, describe how your intervention plan can take advantage of organizational strengths OR propose practical methods for addressing these barriers within your program.

Environment:  Our endocrinology team can save time for the oncology team by providing consults early and seeing these patients in our clinic from the start, for all steroid tapering (once their chemotherapy protocol is complete), assessment of adrenal insufficiency and the proper management.

Resource acquisition:  This extra time spent in clinic will require extra time from health care providers, but as mentioned above, our endocrinology team can take on the bulk of this responsibility in our clinic and will be financially compensated for it.

Resource deployment:   Our endocrinology team can meet with the oncology team in 3-4 sessions and provide education on adrenal suppression 2/2 steroids, including the mechanism, the prevalence of adrenal suppression from steroid use in the pediatric population on chemotherapy, the signs/symptoms to watch for in patients, the dangerous consequences of improperly diagnosed adrenal suppression including adrenal crisis, and how to taper steroids properly and retest the HPA axis to prevent this.  We can present the evidence from the literature thus far to demonstrate why this intervention will be in their patients’ best interest.

Quality centered-care: When we provide education to patients and their families as to why adrenal suppression is a risk and managing it properly is important to their health, this will like increase patient satisfaction, despite extra time spent in clinic and the lab/treatment center.

Assignment 4:

2  Identify an individual (e.g., patient or provider) or group (e.g., community group or organization) that contributes to or is involved in the principal behavior you are attempting to change. Specify the desired behavior change (who needs to change what, when, where and how)?

I think the main group is medical providers (pediatric oncologists, the pediatric oncology nurse practitioners and nurses).

The behavior change is implementing steroid tapers and retesting of the HPA axis with labs, in pediatric oncology patients who have been on a prolonged course of glucocorticoids.

3  Using any of the individual explanatory theories in “Theory at a Glance”, develop an explanatory model for the target behavior (above) that you will be attempting to influence with your intervention.  This can be an extension/based on previously published literature or your best guess of expected findings.  Figures are always very useful... keep it simple. You can also use the logic model of the problem concept as presented in Bartholemew and Mullen (Five roles for using theory and evidence in the design and testing of behavior change interventions). Be sure to include components beyond the individual, such as suggested by the socio-ecological model.

One theory that is applicable to this protocol is the Theory of Planned Behavior.  With this theory, we assume behavioral intentionis the most important determinant of the behavior I am trying to change (i.e. appropriately tapering steroids in each pediatric oncology patient who requires it). We can think of the medical provider’s behavioral intention as being influenced by his or her attitude towards performing the behavior, as well as by their beliefs about whether their colleagues may approve or disapprove of the behavior.  This theory takes into account the medical provider’s perceived behavioral control, meaning their beliefs that they can control this particular behavior and that the behavior is not influenced by factors outside their control.  In this particular case, the tapering of steroids following a specific protocol that is provided is probably something that most providers will think is within their control and thus, they will probably feel confident doing it.  For those who do not see it as something that they can control, they are welcome to obtain a pediatric endocrine consult instead, and the pediatric endocrine team can provide further guidance and monitoring.

3.  Create your own version of Table 1 from Michie et al (Making psychological theory useful for implementing evidence based practice: a consensus approach) that reflects some of the different theoretical domains and interview questions, tailored to the behavior you want to change. Be sure to select several domains likely to be of interest based on the literature or your experience/best guess. 

Assignment 5

April 29, 2015

4  Use the APEASE criteria to identify appropriate intervention functions based on the behavioral diagnosis (See Table 2.3 in Michie et al Chapter 2) 

  3. For one of the intervention functions you selected, select a specific behavior change technique you will employ in your intervention strategy and specify how it will be delivered. See Table 3.3 in Chapter 3 of Behavioral Change Wheel (Michie et al) for list of most frequently used behavior change techniques for each intervention function.

a. BCW Intervention Function: Education - information about health consequences:  I will provide formal teaching of the consequences of not tapering steroids appropriately with pediatric oncology providers and educate them about the dangers of adrenal suppression.

b. Behavior Change Technique:  Persuasion – again through information about health consequences as above.

c. Mode of delivery (i.e., intervention details):  I will provide formal training/lectures about the topic and discuss with providers the consequences of not tapering steroids properly, how the taper can be performed, how to follow up with lab assessment of the adrenal axis, and provide a standard protocol in writing for them to use.

Assignment 6

May 7, 2015

1.  Thinking about the protocol you are developing, identify the process and outcome indicators associated with the intervention/program and briefly describe an approach to measuring each.

The main intervention is providing lectures to the pediatric oncology team about this topic in order to increase awareness and improve practice standards. 

The process indicators are whether or not pediatric oncology providers make note of which patients are on a prolonged course of steroids and chose to address the adrenal issues involved with these patients.  

The outcome indicators are whether or not pediatric oncology patients on chemotherapy are weaned off of steroids gradually and whether the appropriate labs (i.e. ACTH stim test) are checked prior to discontinuation of steroids.   We can measure this by tracking these patients by using ICD-10 codes in EPIC and checking to see if this protocol is being followed in them.

1. Define one or more “intermediate” outcome measures [reflecting changes in environment, organizational culture, systems of care, patient or public behavior, and/or clinician behaviors] that can inform you about the mechanism by which your intervention achieves its downstream effect on health and inform you about the acceptability of your intervention.

Clinician behaviors:   I can develop a survey to assess the pediatric oncology providers’ knowledge of the effects of a prolonged course of steroids on adrenal function and the risks of abrupt discontinuation of steroids, as well as how to appropriately wean and monitor these patients.  I can include in that survey questions to assess the providers’ attitudes towards addressing adrenal issues in their practice (i.e. is it necessary and whether they think they should allocate time for it in their clinic).   Then I can ask providers to complete this survey before and after my intervention (teaching on the topic) and see how much has changed after my intervention.   This will give me more info on how well my intervention was accepted by this team and how likely it is to adopted in their practice.

I will also look at intermediate measures in terms of which portion of pediatric oncology patients are not weaned off of steroids appropriately and if this is different from baseline.

I will also look at what proportion of these patients were rehospitalized for adrenal crisis after the intervetion and if this differs from baseline.

3. Identify a mixed methods study design and briefly describe the quantitative and qualitative data you will collect for program/intervention evaluation.

I would use a mixed methods study design to gather qualitative and quantitative data on how well this protocol has been implemented.  I can do this on a patient level, perhaps 6 -12 months after my intervention with the pediatric oncology team is complete.  I can ask families of patients with h/o chronic steroid use to complete a survey to assess if their children were weaned off the steroids, over what period of time, whether or not they had an endocrine consultation, whether or not they had an ACTH stimulation test, and whether or not their child was hospitalized for any adrenal issues.  This will give me useful information regarding how well my intervention was accepted and implemented, and it’s ultimate success.

Protocol Assignment 7

May 14, 2015

1. Describe the study design you will employ in order to determine if your intervention has had an effect on the outcome variable of interest.

I will use an interrupted time series analysis.  I will collect data before and after the intervention, including different time points after the intervention like immediately after, then 6 months, then 1 year after.  I can perform a logistic regression analysis to determine effects of our intervention at these different time points, focusing on the primary outcome of the proportion of pediatric oncology patients who are inappropriately discontinued off steroids without a proper wean and without proper lab testing. 

2. Define the unit-of-analysis for your main outcome evaluation, the minimum meaningful effect size, and the sample size necessary to detect this effect size.

The unit of analysis will be the pediatric oncology patients who are on a prolonged course of steroids

 The minimum effect size will be a 50% decrease in the proportion of patients who are not placed on an appropriate steroid wean.

Using a sample size calculator based on the student t-test and one-tailed hypothesis, the sample size necessary to detect this effect size of 50% with an alpha of 0.05 and Beta of 0.8 will be 51 patients.