This study protocol was structured based on the SPIRIT 2013 guidelines .
The evaluation is designed as a parallel-group, patient-randomized, multi-center pilot trial in GP-practices in the federal state of Baden-Wuerttemberg, Germany (fig. 2). Patients will be randomized to the intervention and control group to be equally sized (1:1). The intervention group will use the application for six months, the control group will continuously be treated by the standard PraCMan treatment using paper-based symptom protocols. Blinding of either patients or GP-practice teams was not possible due to the character of intervention.
All participating patients as well as GPs and VERAHs in the participating practices take part in the baseline measurement (T0). Patients assigned to the intervention group receive access to ‘TelePraCMan’ within the randomization process and will be using ’TelePraCMan’ for six months. After at least six months, all participants (patients, GPs and VERAHs) will receive a follow-up questionnaire (T1). Furthermore, the patients as well as VERAHs and GPs receive an invitation to report their experiences with ‘TelePraCMan’ in additional interviews within the process evaluation.
The study is being conducted in GP-practices in the federal state of Baden-Wuerttemberg in the south-west of the Federal Republic of Germany. The Department of General Practice and Health Services Research at University Hospital Heidelberg carries out the study and takes the role of the study central office.
‘TelePraCMan’ addresses multimorbid patients who are enrolled in the case management program ‘PraCMan’. Within this study we refer to the most common definition of multimorbidity, which sees multimorbidity as the presence of two or more diseases [27, 28]. Therefore, patients who are suffering from at least two of the following conditions: diabetes mellitus type 2,COPD, high blood pressure and/or heart failure will be included in this study.
Practices eligible for study participation have to be part of the ‘PraCMan’ program for a minimum of six months, covering at least 20 ‘PraCMan’ patients.
For their participation, patients need access to an internet-ready portable device. Furthermore, patients need to be aged 18 years or older and be able to read and speak German and to give consent for study participation. Because both, patients of the control group and of the intervention group, are included in ‘PraCMan’, the basic quality of care remains the same. For the inclusion in ‘PraCMan’, patients must be insured at the sickness fund ‘AOK-Baden-Wuerttemberg’ and have to be enrolled in the general practice-centered care contract .
Patients who do not fit the named eligibility criteria will not be included in this study. The technical affinity of the patients will not influence the inclusion in this study. The requested portable devices may also belong to patients’ relatives who are welcome to help the patients fill in their digital symptom diaries.
‘TelePraCMan’ was developed and programmed by the Department of General Practice and Health Services Research at the University Hospital Heidelberg. The initial objective of developing ‘TelePraCMan’ was to provide the various paper-based symptom diaries of the primary care case-management program `PraCMan’ digitally in an app for smartphone or tablet. In ‘PraCMan’, the patient should keep these symptom diaries between regular monitoring appointments with the VERAH who acts as primary user of ‘PraCMan’ in GP-practices . To integrate GPs, VERAHs, and patients in the development process, focus groups, semi-structured interviews as well as a questionnaire including GPs, care assistants and patients were conducted in order to gain knowledge of user requirements before and alongside the app development process. After the evaluation of the results, the app was adapted and now contains an appointment manager, a manager for target agreements, and the possibility for general practices to access the symptom data via remote access to `TelePraCMan’ besides the initial basic symptom diaries. Furthermore, ‘TelePraCMan’ has been transformed into a web-based application. This means that the application is not installed locally on the user's smartphone or tablet. Instead, data processing takes place on independent web servers (of University Hospital Heidelberg) and access is realized via a web browser on the user's smartphone or tablet which means that an internet connection is required in order to use the app.
`TelePraCMan‘ has four main features: 1) Symptom diaries for diabetes mellitus type 2, blood pressure, heart failure, and COPD, 2) an appointment manager, and 3) a manager for target agreements, which are made individually for each patient within the regular ‘PraCMan’ monitoring in collaboration with GP and VERAH. The symptom diaries were supplemented by 4) a graphic progress display of vital signs and symptoms that have been entered.ain functions of ‘TelePraCMan’ are listed in figure 3.
The patient is expected to actively enter his or her data in ‘TelePraCMan’. An automatic data transmission, e.g. from the blood glucose meter is not provided. By dealing with the data, the patient should gain better awareness of the vital signs and symptoms and the influence his behaviour can have on them . A reminder can be viewed on ballot screen of ‘TelePraCMan’ by user.
To achieve adequate participant enrolment, we financially incentivized participation of GP-practice teams and patients. Practice teams will receive a short training imparting knowledge on the use of ‘TelePraCMan’ and the remote access for GP-practices. Every intervention group participant also receives a step-by-step instruction manual and a configuration checklist from his GP-practice. The configuration of symptom diaries (selection of diaries, limit and target values, diary rhythm) and target agreements are individually negotiated by patient, VERAH and GP. The patient then configures ‘TelePraCMan’ using the configuration checklist, which contains the negotiated settings.
Effects on the patients’ health related quality of life during the 6-months intervention period will be assessed using the German version of the Short Form 12 Health Questionnaire (SF-12 ). This outcome will be collected at baseline at the beginning of the intervention (T0) and after six months at the end of the intervention (T1).
Secondary outcomes for participation patients are defined as follows:
- The patients’ self-management capabilities is measured using the German version of the "Patient Activation Measure" (PAM13-D ). Self-management is the hypothesized moderating variable between usage of ‘TelePraCMan’ and health-related quality of life according to the rationale that self-management respectively empowerment results into a better health-related quality of life. Studies showed an association between higher patient activation and a better health related quality of life [32–34].
- A questionnaire to general technical affinity (TA-EG ) of participating patients and a smartphone usage questionnaire (self-administered) aim to measure the general openness towards and acceptance of new or digital technology like mHealth-interventions. The self-administered smartphone usage questionnaire is a 13-items instrument that collects ownership (yes/ no), purchase (self-bought/ receive as present/ other), and frequency of use in everyday life as well as one item set about frequency of use of various smartphone functions (5-point Likert scale with response options from ‘never’ to ‘very often’).
- The objective number and frequency of use of ‘TelePraCMan’ by patients is determined by log-in data of users.
- Patients’ user experience of ‘TelePraCMan’ is measured by the User Experience Questionnaire (UEQ ).
- Identification of general support needs and/or potential persons giving support in dealing with ‘TelePraCMan’ or technical problems. This self-administered questionnaire is a 9-items instrument that measures what kind of support (e.g. family members, manual, or without support) is used in case of technical problems and how often it used. All items rated with a 7-point Likert scale with response options from ‘never’ to ‘always’.
- Sociodemographic data.
Secondary outcomes concerning GP-practice side (GPs and VERAHs) are:
- The general technical affinity of participating GPs and VERAHs measured with the TA-EG questionnaire .
- Perception and acceptance of ‘TelePraCMan’ by GPs and VERAHs and the compatibility with GP-practices workflows are measured with a self-administered 21-items questionnaire at baseline (T0) and a 30-items questionnaire at follow-up (T1). All items rated with a 5-point Likert scale with response options from ‘disagree’ to ‘strongly agree’. Furthermore, there is a field for 'no statement' for each item. The follow-up questionnaire (T1) offers several fields for open answers.
- Sociodemographic data.
After finalizing the 6-months intervention period, a qualitative process evaluation consisting of semi-structured interviews with GPs, VERAHs and patients is planned to investigate the experiences made with ‘TelePraCMan’ during practical use.
Table 1 shows the enrolment, and the points of outcomes assessment.
In order to be able to calculate a meaningful sample size for the study, recommendations refer to include at least 50 participants per arm to achieve a power of 80% and an effect size of d < 0.1 (2-side significance level of 5%) . For the randomized trial we assumed a small effect size because studies measuring health-related quality of life with SF-12 with comparable populations showed no significant effects after four month  or showed significant effects at the earliest after 24 month . Since the randomized study in this case has a duration of only six months, a lower effect would suffice as an indication of the effectiveness of ‘TelePraCMan’. Because the heterogenous combination of chronically diseases by multimorbid probands and a drop-out rate up to 26% in studies with comparable interventions [16, 38], we operate with a total of 100 participants per arm in order to be able to consider a spectrum of chronically disease combinations as broad as possible in a later subgroup analyses. A comparable intervention study in a similar population and setting shows an intracluster correlation (ICC) of 0,01 at practice level . This minimal effect has no noticeable influence on the power, so that we do not explicitly calculate the design effect D . In conclusion, a total of 100 patients per arm is targeted.
To reach the sample size, hundred selected GP-practices participating in ‘PraCMan’ will be informed by letter and/or fax about the study and will be asked for their support in patient recruitment and study conduction. Practices size and geographical closeness are primary selection criteria. The aim is to recruit a maximum of 20 GP-practices with a sufficient number of ‘PraCMan’ patients from all over the federal state of Baden-Wuerttemberg.
The recruitment of the participating patients is carried out by the GP-practices. Patients who meet the inclusion criteria will be addressed by the participating GP-practices and will be informed verbally about the aim and content of the study by the VERAH. If the patient is interested to participate in the study, he receives two sets of information material – one for the intervention group and one for the control group. After reading the information material, the patient can formally agree to participate in the study, knowing that due to the randomization process he might end up in either in the intervention or in the control group.
Before study enrolment, practice teams will receive a short training imparting knowledge on the use of ‘TelePraCMan’ as well as on the recruitment and randomization processes.
Interviews with GPs, VERAHs and patients will be conducted after completing the 6-months intervention period, to evaluate the implementation strategy. For this, patients participating as part of the intervention group receive a letter from their GP-practice containing the T1-questionaire as well as an invitation to participate in an interview dealing with their ‘TelePraCMan’-experiences. Patients interested in interview participation are asked to directly contact the study central office.
Furthermore, participating GPs and VERAHs will be recruited for semi-structured interviews after the first patient the practice recruited finishes the 6-months intervention period.
Patients’ and practice team members’ interview participation will be financially rewarded.
Randomization of the patients is executed by practice staff on patient level. After the patients give consent to study participation, they will be handed out sealed envelopes with the corresponding group membership. The sealed envelopes will be prepared by the study central office beforehand ensuring that their content cannot be inspected by the GP-practices until they are opened by the patients. For the randomization, patients are randomly assigned to either the intervention or the control group by lot. This procedure is constructed to result in equally sized groups. Blocks of ten Patient-IDs will be individually matched with five control-group and five intervention-group notes.
Because the intervention cannot be blinded, all study members are able to know the group assignment of a patient from the moment of opening the envelope on. This is necessary to perform all further processes in this study as guarding the patient within the installation process as well as comparing data of the two study groups.
Data collection and management
Paper-based questionnaires for participating patients at baseline (T0) and follow-up (T1) are stored in the Investigator Site File (ISF) in the GP-practices. With recruitment and allocation, the patients receive the baseline questionnaire (T0) and a post-paid envelope. The completed questionnaires will be sent by mail to the study central office by patients. After six months, the GP-practice will be given the follow-up questionnaire (T1) and a post-paid envelope to the patient, who sends the filled in questionnaire by mail to the study central office, too.
The paper-based questionnaires for participating GPs and VERAHs at baseline (T0) and a post-paid envelope are handed out to GP-practice teams at the enrolment in study face-to-face or by mail by researchers of the study central office. With the mail for recruitment to the interviews for the process evaluation, the GP-practice teams receive the follow-up questionnaire (T1) and a post-paid envelope, to send the completed questionnaire via mail to the study central office. Paper-based documents will be stored in the study central office at the Department of General Practice and Health Services Research at University Hospital Heidelberg.
Semi-structured interviews will be conducted as face-to-face or telephone interviews by researchers of the study central office. The estimated duration for the interviews will be a maximum duration of one hour. All interviews will be audio-recorded, transcribed verbatim and stored on servers of the University Hospital Heidelberg. The transcripts of interviews will contain pseudonymized data only.
Data will be analyzed in accordance with the CONSORT-EHealth V1.6.2. statement . Intention-to-treat analysis will be performed in the primary analysis. Descriptive statistics will be used to summarize characteristics of staff of GP-practices and participants by group. The primary and secondary outcomes at follow-up will be compared between study arms, adjusted for baseline values and potential confounders in a multiple regression analysis. To explore the impact of contextual factors (differences between participating practices, sociodemographic data of the patients such as age and number of chronic conditions, group affiliation, timepoint of data collection (T0 vs. T1), etc.), we will apply a multilevel regression that considers the hierarchical structure of data . If needed, comparisons of specific variables on outcome level between the control and the intervention group and the two collection time points (T0 and T1) will be conducted using t-test or a non-parametric testing equivalent depending on the individual characteristics of the variables such as the scale level. Quantitative data analysis will be conducted using the statistical programs R, Excel and SPSS Version 25.
Additional sensitive analyses will be conducted as per-protocol analysis in the intervention group (i.e. regular users of the intervention).
Missing data of multi-item scales will be handled according to questionnaire guidelines. In case of missing data in SF-12 no score can be calculated due the weighting of the questions . If no guideline is available for the other questionnaires, then items will be imputed with the Expectation-Maximization-Algorithm.
The qualitative data collected via semi-structured interviews at close-out will be fully transcribed and a deductive thematic content analysis  will be conducted, guided by the checklist for ‘Tailored Implementation for Chronic Diseases’ (TICD)  using the framework method [45.