Results Summary

What was the research about?

Sickle cell disease, or SCD, causes red blood cells to change shape and block blood flow, causing pain or damage to the body. Hydroxyurea, or HU, is a treatment that helps keep red blood cells healthy. But many patients find it hard to take HU every day. Some worry that it won’t help or will cause side effects.

In this study, the research team looked at whether encouraging adults and children with SCD helped them take HU every day. Patients and parents earned $1 every day that they uploaded a video for the research team of themselves taking an HU pill. The team sent reminders daily and followed up if patients had not uploaded a video three times in the past month. They encouraged patients by phone, text, or in person. Patients received reminders for one year.

The research team compared patients who got encouragement with those who received usual care. In usual care, adults with SCD and children with SCD and their parents received reminders about clinic visits and help paying for transportation.

What were the results?

Patients who got encouragement and patients who received usual care didn’t differ in

  • How often they said they took HU
  • The proportion of days they had HU pills available from their prescription each month

After six months, patients who received encouragement to take HU had more red blood cells that were healthy than patients who received usual care. But by one year, there was no difference. Compared with children who got usual care, children who got encouragement had less pain and anxiety.

Patients receiving encouragement uploaded videos an average of 34 percent of days. Patients said the video system and reminders worked well, but they sometimes didn’t want to record videos.

Who was in the study?

The study included 79 adults with SCD and 85 children with SCD and their parents. Among adults, 96 percent were black; 4 percent identified as Latino. The adult average age was 24, and 55 percent of adults were men. Among children, 96 percent were black; 2 percent identified as Latino. The average age was 13, and 45 percent of children were boys.

All patients received treatment at one of three hospitals and had a prescription for HU for at least six months before the study.

What did the research team do?

The research team assigned patients by chance to get usual care or encouragement to take HU.

Using pharmacy records, the research team tracked how often patients filled their HU prescriptions and had HU available. Patients or parents completed surveys at the start of the study and 6 and 12 months later. The surveys asked how often patients took HU, and about pain, fatigue, and sleep. The team also looked at hospital records to see how often patients went to the hospital with pain or other problems caused by SCD. Finally, the team interviewed some patients and parents to find out how they felt about uploading the videos.

Youth and adults with SCD, parents of youth with SCD, and SCD community groups helped plan and conduct the study.

What were the limits of the study?

The research team couldn’t get pharmacy records for all patients, and 26 percent of patients stopped taking part in the study. Some patients got HU refills in the hospital. As a result, the patients might have had HU available more, or less, often than the research team knew.

Future research could compare other ways to help people with SCD take HU regularly.

How can people use the results?

Clinics that care for people with SCD can use these results when considering ways to help people take daily treatment.

Final Research Report

View this project's final research report.

More About This Research

Peer Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:

  • The reviewers asked that the report give more attention to the difficulty of obtaining sufficient data from subjects for this study, noting that the reminder intervention seems a positive tool.  However, they explained that the mobile directly observed therapy (MDOT), requiring subjects to submit videos when taking medication, raised issues of privacy, ease of use, and effectiveness. The researchers added discussion to the report about the limitations of the study’s approach and the intrusiveness of MDOT. They noted that adherence to the study protocol of submitting videos may underestimate the participants’ adherence in taking hydroxyurea (HU) therapy because participants did not always send a video when they took HU.
  • Reviewers suggested that reframing the research as a mixed-methods study would be beneficial. The reviewers explained that in this type of study, the qualitative findings could better enhance the quantitative results, which the sample size limits. The researchers explained that while they reached thematic saturation in the qualitative analysis, it concerned them that this would be lost when conducting quantitative subgroup analyses, and they preferred to keep the analyses separate.
  • Reviewers noted that different types of sickle cell disease (SCD) produce different challenges and needs. They wondered if more insights would have been gleaned if this study identified patients by type of SCD. The researchers agreed that patients with different forms of SCD might have different responses to HU but said that this study did not have the statistical power to distinguish impact in patients with different types of SCD.
  • Reviewers noted that the rate of video submission seemed poor, and that the researchers’ use a rate of 25 percent adherence cut point to categorize groups seemed too low. The researchers acknowledged that they did not set a priori an adequate level of adherence for video submission, since there were no previous standards for this.  They explained that 25 percent was much lower that what previous research has set as a benchmark for good medication intake adherence (e.g., 80 percent). However, as they learned from qualitative interviews that participants often took medications but did not submit videos, they determined post hoc that the appropriate inflection point categorize groups was 25 percent adherence with video submission.

Conflict of Interest Disclosures

View the COI disclosure form.

Peer-Review Summary

Peer review of PCORI-funded research helps make sure the report presents complete, balanced, and useful information about the research. It also assesses how the project addressed PCORI’s Methodology Standards. During peer review, experts read a draft report of the research and provide comments about the report. These experts may include a scientist focused on the research topic, a specialist in research methods, a patient or caregiver, and a healthcare professional. These reviewers cannot have conflicts of interest with the study.

The peer reviewers point out where the draft report may need revision. For example, they may suggest ways to improve descriptions of the conduct of the study or to clarify the connection between results and conclusions. Sometimes, awardees revise their draft reports twice or more to address all of the reviewers’ comments. 

Peer reviewers commented, and the researchers made changes or provided responses. The comments and responses included the following:

  • The reviewers asked that the report give more attention to the difficulty of obtaining sufficient data from subjects for this study, noting that the reminder intervention seems a positive tool.  However, they explained that the mobile directly observed therapy (MDOT), requiring subjects to submit videos when taking medication, raised issues of privacy, ease of use, and effectiveness. The researchers added discussion to the report about the limitations of the study’s approach and the intrusiveness of MDOT. They noted that adherence to the study protocol of submitting videos may underestimate the participants’ adherence in taking hydroxyurea (HU) therapy because participants did not always send a video when they took HU.
  • Reviewers suggested that reframing the research as a mixed-methods study would be beneficial. The reviewers explained that in this type of study, the qualitative findings could better enhance the quantitative results, which the sample size limits. The researchers explained that while they reached thematic saturation in the qualitative analysis, it concerned them that this would be lost when conducting quantitative subgroup analyses, and they preferred to keep the analyses separate.
  • Reviewers noted that different types of sickle cell disease (SCD) produce different challenges and needs. They wondered if more insights would have been gleaned if this study identified patients by type of SCD. The researchers agreed that patients with different forms of SCD might have different responses to HU but said that this study did not have the statistical power to distinguish impact in patients with different types of SCD.
  • Reviewers noted that the rate of video submission seemed poor, and that the researchers’ use a rate of 25 percent adherence cut point to categorize groups seemed too low. The researchers acknowledged that they did not set a priori an adequate level of adherence for video submission, since there were no previous standards for this.  They explained that 25 percent was much lower that what previous research has set as a benchmark for good medication intake adherence (e.g., 80 percent). However, as they learned from qualitative interviews that participants often took medications but did not submit videos, they determined post hoc that the appropriate inflection point categorize groups was 25 percent adherence with video submission.

Conflict of Interest Disclosures

Project Information

Lakshmanan Krishnamurti, MD
Emory University^
$2,148,331
10.25302/05.2020.CE.13046859EM

Key Dates

53 months
September 2013
February 2019
2013
2018

Study Registration Information

^Lakshmanan Krishnamurti was affiliated with the University of Pittsburgh when this project was funded.

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Last updated: October 20, 2021