The Impact of Preoperative FoodforCare at Home on Nutritional and Functional Outcomes
Phase: NA
Conditions: Surgery
Sponsor: Radboud University Medical Center

Document date: 02-01-2018 
 
 
 
 
 
 
 
The impact of a home delivered meal service in 
the preoperative setting; a randomized study. 
 
 
 
 
 
 
 
 

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Protocol ID 
De impact van preoperatief FoodforCare Thuis op 
functionele en klinische uitkomstmaten; een 
gerandomiseerde studie. 
Short title 
Preoperatief FoodforCare Thuis 
Version 
2.0 
Date 
02-01-2018 
Coordinating 
investigator/project leader 
Vera IJmker-Hemink 
Diëtist-onderzoeker 
Afdeling Maag-, Darm- en 
Leverziekten, Diëtetiek en Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
Principal 
investigator(s) 
Dr. G.J.A. Wanten, MD, 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en leverziekten, Diëtetiek en 
Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
Dr. M.G.A van den Berg 
Themaleider voeding/diëtist/ 
wetenschappelijk onderzoeker 
Afdeling Maag-, Darm – en leverziekten, 
Diëtetiek en Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
Sponsor 
FoodforCare Foundation 
Subsidising party 
FoodforCare Foundation 
Independent expert (s) 
Dr. D.J. de Jong 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en leverziekten, Diëtetiek 
en Darmfalen 
Radboudumc, Postbus 9101, HP 455 
6500 HB Nijmegen 
Laboratory sites 
Nvt 
Pharmacy 
Nvt 

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PROTOCOL SIGNATURE SHEET 
 
Name 
Signature 
Date 
Head of 
Department 
Prof. Dr. J.P.H. Drenth, MD, 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en 
Leverziekten, 
Radboudumc, Postbus 9101,HP 
455 6500 HB Nijmegen 
Principal 
investigator(s) 
Dr. G.J.A. Wanten, MD, 
Maag-, Darm-, Leverarts 
Afdeling Maag-, Darm – en 
Leverziekten, 
Radboudumc, Postbus 9101, 
HP 455 6500 HB Nijmegen 
 
 

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Inhoud 
1. INTRODUCTION AND BACKGROUND ................................................................................................... 6 
2. OBJECTIVES .......................................................................................................................................... 7 
3. STUDY DESIGN ..................................................................................................................................... 8 
3.1 Recruitment ............................................................................................................................... 8 
3.2 Randomization and blinding ...................................................................................................... 8 
4. STUDY POPULATION ............................................................................................................................ 9 
4.1 Population ................................................................................................................................. 9 
4.2 Inclusion criteria ........................................................................................................................ 9 
4.3 Exclusion criteria ....................................................................................................................... 9 
4.4 Sample size calculation .............................................................................................................. 9 
5. INTERVENTION .................................................................................................................................. 10 
5.1 Name and description of investigational products ................................................................. 10 
5.2 Summary of findings from clinical studies .............................................................................. 10 
5.3 Summary of known and potential risks and benefits .............................................................. 10 
5.4 Dosages, dosage modifications and method of administration .............................................. 10 
6. METHODS .......................................................................................................................................... 12 
6.1 Primary outcome ..................................................................................................................... 12 
6.2 Secondary outcomes ............................................................................................................... 12 
6.3 Other outcomes....................................................................................................................... 13 
6.4 Study procedure ...................................................................................................................... 14 
6.5 Withdrawal of individual subjects ........................................................................................... 14 
6.6 Replacement of individual subjects after withdrawal ............................................................. 14 
6.7 Follow-up of subjects withdrawn from treatment .................................................................. 14 
6.8 Premature termination of the study ....................................................................................... 14 
7. PATIENT SAFETY ................................................................................................................................ 15 
7.1 Section 10 WMO event ........................................................................................................... 15 
7.2 AEs, SAEs and SUSARs ............................................................................................................. 15 
7.3 Follow-up of adverse events ................................................................................................... 16 
8. STATISTICAL ANALYSIS ....................................................................................................................... 17 
8.1 Descriptive statistics ................................................................................................................ 17 
8.2 Primary study parameter(s) .................................................................................................... 17 

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8.3 Secondary study parameter(s) ................................................................................................ 17 
9. ETHICAL CONSIDERATIONS ............................................................................................................... 18 
9.1 Regulation statement .............................................................................................................. 18 
9.2 Recruitment and consent ........................................................................................................ 18 
9.3 Objection by minors or incapacitated subjects ....................................................................... 18 
9.4 Compensation for injury .......................................................................................................... 18 
9.5 Incentives ................................................................................................................................ 18 
10. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION ...................................................... 19 
10.1 Handling and storage of data and documents ...................................................................... 19 
10.2 Monitoring and Quality Assurance ........................................................................................ 19 
10.3 Amendments ......................................................................................................................... 19 
10.4 Annual progress report ......................................................................................................... 19 
10.5 End of study report ................................................................................................................ 19 
10.6 Public disclosure and publication policy ............................................................................... 20 
11. STUCTURED RISK ANALYSIS ............................................................................................................. 21 
11.1 Potential issues of concern.................................................................................................... 21 
11.2 Synthesis ................................................................................................................................ 21 
12. REFERENCES .................................................................................................................................... 22 
 
 
 
 

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SUMMARY 
Background: Various approaches in the preoperative setting have demonstrated a positive 
effect on nutritional status and reduction of complications.  
Objective: To investigate whether protein-rich nutrition of FoodforCare in the preoperative 
setting improves functional outcomes within 3 weeks in surgical patients, compared to usual 
care. 
Study design: Randomized controlled trial 
Intervention and procedure: Surgical patients are screened at the preoperative out-patient 
clinic for risk of malnutrition by nurses. In case of a score ≥ 1, which indicates a risk for 
malnutrition and a potential participant, patients are asked to participate. Participants 
randomized to the intervention group will receive the FoodforCare service in the preoperative 
setting for 3 weeks, which consists of five to six small protein and energy-rich meals. After an 
individual intake, the composition of the dishes will be tailored to the needs of the patient in 
terms of composition, diet, taste, flavor and portion size. Participants randomized to the 
control group will continue their usual diet in the preoperative setting for 3 weeks.  
Main study parameters/endpoints: The primary outcome is the change in handgrip 
strength (between baseline and end of the intervention) between the 2 groups. Secondary 
outcomes include change in nutritional status, nutritional intake, patients’ satisfaction, quality 
of life, length of stay and postoperative complications.  
Nature and extent of the burden and risks associated with participation, benefit and 
group relatedness: There are no additional tests or hospital tests necessary for the patient. 
This study will not confer any no additional risks. Food will be delivered within the expiration 
dates and the meals will be prepared according to the regular hygienic and food safety 
criteria that are valid. Possible serious reactions to the meals will be noted as SAE’s. 
 
 

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1. INTRODUCTION AND BACKGROUND 
 
Each year, approximately 1.4 million patients in the Netherlands are operated.(1) Adequate 
nutritional intake, mainly protein intake, before surgery is important to improve preoperative 
muscle strength and functional capacity. However, up to 40% of patients admitted to the 
hospital suffer from malnutrition and this further deepened during hospitalization(2), which is 
an independent risk factor for peri-operative morbidity and severe complications(3), ranging 
from increased muscle loss, to higher infection rates, delayed wound healing and 
subsequently a prolonged hospital stay.(4) Recent studies also reported a higher rate of 
postoperative complications in patients with respectively a low muscle mass, assessed using 
computed tomography (CT), or muscle weakness, defined by handgrip strength, 
preoperatively.(5, 6) These malnutrition-related complications have a major impact on 
hospital resources and healthcare costs.(7)  
 
There are various types of approaches used in the hospital setting to optimize the nutritional 
status and improve functional capacity of hospitalized (surgical) patients.(8, 9) In enhanced 
recovery programs, which aims to ameliorate the response to surgery, various nutrition-
specific aspects are included such as preoperative nutrition risk screening and carbohydrate 
loading, early feeding of normal food and inclusion of oral nutritional supplements prior to 
operation and for at least the first 4 postoperative days.(10) An adequate food service is 
another strategy to improve protein intake and thereby the nutritional status. An innovative 
hospital food formula, FoodforCare, is recently developed and implemented hospital-wide in 
the academic hospital (Radboudumc) in Nijmegen. This formula consists of small protein-rich 
dishes served 6 times a day, that aims at improving appetite and contributing to patients’ 
wellbeing. Recent publication shows that FfC improves reached protein and energy 
requirements, compared to the standard food service.(11) Extension of the study period to 
the out-of-hospital setting is recommended to explore the effects of long-term exposure to 
this concept on clinical outcomes.    
 
However, research has mainly focused on approaches in the postoperative period and during 
hospital stay, while evidence shows that this phenomenon might also be relevant in the 
preoperative setting.  
A recent meta-analysis shows that preoperative nutritional support with parenteral nutrition 
improves clinical outcomes, such as length of stay and postoperative complications, in 
abdominal surgical patients at nutritional risk.(12) Another study shows that meaningful 
changes in postoperative functional exercise can be achieved with a prehabilitation 
program.(13) Studies on preoperative protein-rich diets are lacking. 
 
Since FoodforCare has proven to increase nutritional intake in the hospital setting, we aim to 
determine whether protein-rich nutrition of FoodforCare in the preoperative setting improves 
functional outcomes within 3 weeks in surgical patients at risk for malnutrition, compared to 
usual care. We expect that this diet will have a beneficial effect on protein intake and 
therefore, on the nutritional status of the patients. Another positive effect might result from a 
reduction in postoperative complications. 
 
 
 
 
 
 

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2. OBJECTIVES 
 
2.1 Primary objectives: 
To investigate whether protein-rich nutrition of FoodforCare in the preoperative setting 
improves functional outcomes within 3 weeks in surgical patients at risk for malnutrition, 
compared to usual care. The primary functional outcome is determined as the difference in 
handgrip strength between baseline and the end of intervention. 
2.2 Secondary objectives: 
To investigate whether protein-rich nutrition of FoodforCare in the preoperative setting 
improves: 
1. Functional status: Short Performance Physical Battery 
2. Nutritional status (weight, Patient Generated Subjective Global Assessment (PG-
SGA)) 
3. Protein- and energy-intake relative to requirements 
4. Length of stay, number of readmissions and postoperative complications 
5. Quality of life 
6. Satisfaction of patients regarding food quality (and service when FoodforCare) 
 
 

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3. STUDY DESIGN 
This is a randomized controlled trial (RCT). Given the nature of the intervention it is not 
possible to blind participants and investigators. This study will be conducted at the Radboud 
University Medical Center. This study will be directed according to the principles of the World 
Medical Association Declaration of Helsinki (64th WMA General Assembly, October 2013).  
3.1 Recruitment 
Surgical patients will be screened at the preoperative out-patient clinic for risk of malnutrition 
with the MUST (Malnutrition Universal Screening Tool) score by nurses. In case of a score ≥ 
1, which indicates a risk for malnutrition and a potential participant, nurses will ask the 
participant whether they are happy to receive information about the study and will 
subsequently call the coordinated researcher. The researcher will conduct the initial 
screening and will inform the patient about the study. The patient will also be informed that 
participation is voluntary and withdrawal is possible at any time. The patient will receive an 
information leaflet with further information. A minimum of 24 hours later the researcher will 
contact the patient by telephone and ask whether he/she will participate in the study. After 
that, the informed consent form will be signed by the patient and send to the researcher, who 
will register the patient. The medical attending staff provided permission to approach 
individual patients. 
 
3.2 Randomization and blinding 
The researcher will randomize the patient by using a password-protected randomization 
service which is part of the clinical data management system ‘’Research Manager’’. 
Participants are randomized to either the intervention or the control group, using block 
randomization, stratified for underlying disease and MUST score (MUST1 or MUST>1). After 
randomization, the system provides a trial participants number, who will be documented in a 
designated source document with the patient information. The study number and birth date 
will be listed on all study documents. Blinding seems not possible for the coordinating 
researcher, since one group will receive FoodforCare and the other group will receive no 
additional products. Whether blinding is possible for the researcher will be examined during 
the pilot study. In that case, patients will be asked not to tell the researcher in which group 
they are allocated. Patients have to be aware of the group allocation. Any important protocol 
modifications will be communicated with the Medical Ethics Committee.  
 
Figure 1. Study design 
 
 
T0 
Screening 
T1 
Baseline 
FoodforCare 
T2 (week 3) 
End of intervention 
T3 
30 days after 
surgery 
Usual care 
T2 (week 3) 
End of intervention 
T3 
30 days after 
surgery 

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4. STUDY POPULATION 
 
4.1 Population 
The study population consists of Dutch speaking patients undergoing surgery with a risk for 
malnutrition (MUST≥1), with oral intake, living within a radius of 40km from the Radboudumc. 
Patients on tube- or parenteral feeding, patients with renal insufficiency (MDRD-GFR < 
60ml/min and/or proteinuria) or patients with impairment, which would prohibit the patient 
from full participation in the study, were excluded from the study. 
4.2 Inclusion criteria 
 
18 years or older 
 
MUST score ≥ 1 
 
living within a 40 km radius around Nijmegen/Veghel 
 
inclusion at least 4 weeks before surgery 
 
oral intake 
 
surgery: Urology, Orthopedics, colorectal and oesophagus. 
 
4.3 Exclusion criteria 
 
renal insufficiency (MDRD-GFR (glomerular filtration rate) < 60ml/min and/or 
proteinuria)* 
 
underlying condition which makes it unpossible to perform hand grip strength 
 
*proteinuria is defined in case of a protein creatinine ratio > 0.5g/10mmol or an albuminuria > 
300mg/day. 
 
4.4 Sample size calculation  
The sample size calculation is based on the primary outcome of this study: the change in 
handgrip strength after 3 weeks between the groups. Based on literature and data from our 
previous study, patients will have a baseline handgrip strength of 28kg with a standard 
deviation of 5kg.(6) Assuming a difference of 2kg (7%) is a clinically relevant difference in 
favor of FoodforCare, we estimate that 209 patients are needed in order to obtain a power of 
80% (two-tailed t-test, alpha 0.05). 251 patients should be included, assuming a drop-out 
rate of 20%. In order to improve the power significantly, we will make use of the ANCOVA 
test. By multiplying the number of patient with (1-(ρ²)) a total of 228 patients will be needed. 
The correlation between the baseline and end of treatment (ρ) is estimated at 0.3, also 
because of the heterogeneity of the substantiated studies. 
 
 

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5. INTERVENTION 
 
5.1 Name and description of investigational products 
The FoodforCare at Home concept consists of five to six small protein and energy enriched 
meals that will be delivered twice a week. After an individual intake, the composition of the 
dishes will be tailored to the needs of the patient in terms of composition, diet, taste, flavor 
and portion size. Besides the meals, patients in the intervention group will also receive an 
information leaflet about the importance of protein during treatment and how to reach their 
protein requirements. The control group has no restrictions to their diet. The dishes are 
prepared by caterer Maison van den Boer, meeting the highest standards of nutrition and 
quality and served according to the regular hygienic and food safety criteria that are valid, 
and delivered twice a week by FoodforCare.  
5.2 Summary of findings from clinical studies 
Uit recente literatuur komt naar voren dat adequate preoperatieve voedingsondersteuning 
resulteert in betere klinische resultaten. Een recente meta-analyse uit 2015, bestaande uit 
gerandomiseerde, gecontroleerde trials, heeft gekeken naar het effect van preoperatieve 
voedingsondersteuning op klinische uitkomsten in ondervoede patiënten(14) Het betrof 
voornamelijk gastrointestinale chirurgie met parenterale therapie. Er werd geconcludeerd dat 
de ondersteuning superieur was voor wat betreft het verbeteren van klinische uitkomsten, 
onder andere in het verminderen van postoperatieve complicaties en verminderen van de 
opnameduur. 
Een andere studie uit 2012 toonde aan dat preoperatieve voedingssupport (minimaal 7 
dagen parenterale of enterale voeding) bij abdominale chirurgische patiënten met een 
verhoogd risico op ondervoeding (NRS 5 of hoger), leidde tot een significante vermindering 
in complicaties en opnameduur, ten opzichte van de controle groep.(15) 
Daarnaast wordt er in het ERAS (enhanced recovery after surgery) protocol onder andere 
beschreven op welke manier uitkomsten na chirurgische ingreep kunnen worden verbeterd. 
Hierbij wordt gestreefd naar minimale stress rondom de operatie. Koolhydraat drankjes 
preoperatief lijken hierbij effectief in het verminderen van postoperatieve insuline 
resistentie.(9, 10) 
5.3 Summary of known and potential risks and benefits 
The food products of Maison van den Boer meet the highest standards of nutrition and 
quality and has therefore, no additional risk compared to usual products. All products will be 
served according to the regular hygienic and food safety criteria that are valid. Possible 
serious reactions to the products will be noted as SAE’s. There are no additional tests or 
hospital visits necessary for the patient. Therefore, we do not expect any potential risk.   
 
5.4 Dosages, dosage modifications and method of administration 
The composition of the dishes are developed to enable maintenance and if possible 
improvement of the nutritional status of the patient. The aim is, therefore, to stimulate protein 
intake as much as possible with a protein intake of at least 1.2 gram per kilogram bodyweight 
per day. On average, this is equivalent to an intake of 90-95 grams of protein per person per 
day (assuming an average weight of 75-80 kg). Protein intake of 20-25 grams per meal 
would ensure optimal postprandial protein synthesis in the muscles.(14) This and other 

11 
 
information about the protein content of the FoodforCare products will be spread to the 
patients in order for them to make decisions that contribute to their protein requirements. 

12 
 
 
6. METHODS 
6.1 Primary outcome 
The primary outcome is the change in handgrip strength (between baseline and end of 
treatment) between patients receiving FoodforCare and patient on usual care (table 1).  
Handgrip strength  (HGS) is a valid non-invasive method to measure muscle functionality 
and serves as a predictor for the overall muscle strength, nutritional status and change in 
nutritional status of  patients.(15) Importantly, studies have shown that impaired handgrip 
strength may be an indicator of increased mortality and morbidity, such as increased 
postoperative complications, length of stay, readmissions, and decreased physical status.(6, 
16) HGS will be measured with the JAMAR meter on a standardized manner for the 
researcher.(17) Whether blinding is possible for the researcher will be examined during the 
pilot study. 
6.2 Secondary outcomes 
- 
Functional status: besides HGS, change in functional status will be evaluated with the 
Short Physical Performance Battery. 
- 
Nutritional status: change in nutritional status will be assessed with the PG-SGA and 
measurements of body weight (table 1).(18) PG-SGA will be filled in by the patient 
and a member of the research team. Body weight will be measured on a calibrated 
weighting scale (type ..) in sober state. Relative weight changes will be presented as 
the percent weight change relative to the weight at baseline. Body Mass Index will be 
calculated. 
- 
Nutritional intake: difference in nutritional intake (protein and energy) will be 
evaluated at every time point based on a 2-day food diary filled in by the patient. The 
food diary will be cross checked by a member of the research team and, if necessary, 
the patient will be called for clarification. The food items will be coded and calculated 
according to the Dutch Food Composition Table (NEVO, RIVM). During the pilot 
study, we will evaluate if a ‘’symptom diary’’ should be assessed.  
- 
Length of hospital stay and readmission: reported from the medical record of the 
patients. 
- 
Postoperative complications: reported from the medical record of the patients and 
classified using the Clavien-Dindo classification.(19) Grade of severity is based on 
the type of treatment for the specific complication. Infectious complications will be 
reported based on the definition of the American College of Chest Physicians/Society 
of Critical Care Medicine Consensus Conference.(20) 
- 
Quality of life: change of quality of life will we assessed with the SF-36 questionnaire 
filled in by the patients. The Caregiver Reaction Assessment will be filled in by their 
caregiver.(21) 
- 
Patient satisfaction:  
o Both groups will fill in a questionnaire with questions about their wellbeing and 
stress level regarding shopping and cooking of their meals.  
o In the intervention group, the Net Promoter Score (NPS) with additional 
questions will be used to assess patient satisfaction in the intervention group 
at time point 3. The NPS is determined by asking the question: ‘How likely is it 

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that you would recommend FoodforCare to a friend or colleague?’. The score 
ranges from 1-10 and patients can be grouped in ‘promoters’ (9-10 grading), 
‘passively satisfied’ (7-8 grading) and ‘criticasters’ (0-6 grading). The NPS is 
finally calculated by subtracting the percentage of criticasters from the 
percentage of promoters.(22) Additional questions about satisfaction with 
respect to the food supply and logistics of FoodforCare will be answered by 
the patients to explain their score.  
Both questionnaires are self-composed and based on validated questionnaires 
because there is no     Dutch validated questionnaire available about a home-
delivered meal service. 
 
6.3 Other outcomes 
 
- 
MUST: the Malnutrition Universal Screening Tool will be used at baseline and end of 
treatment (T2) to determine the risk of malnutrition.  
- 
Adverse events: Possible adverse events including nausea, vomiting and gastrointestinal 
complaints will be identified by the ‘’symptom diary’’. Unless we do not expect serious 
adverse events to occur, patients will be asked to contact a staff member and the 
researcher directly when adverse events occur. We will only report (serious) adverse 
events that have a possible causal relationship with the given food products till the end of 
the study. All AEs will be followed until they have abated, or until a stable situation has 
been reached. 
 
 
Table 1. Measurements at each time point 
T0 
 
T1 
T2 
T3 
Preoperative 
out-patient 
clinic 
Contact by 
telephone 
Baseline 
End of 
treatment 
30 days 
after 
surgery 
Patient information 
X 
Informed consent 
X 
Randomization 
X 
Handgrip strength 
X 
X 
Weight 
X 
X 
PG-SGA 
X 
X 
   Nutritional intake 
X 
X 
Satisfaction 
X 
SF-36 
X 
X 
  X 
SPPB 
X 
X 
  X 
Postoperative 
complication
X 
Adverse events 
X 
X 
  X 

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6.4 Study procedure 
A number of things will be set in motion after the patient signs the informed consent. As 
described earlier, the researcher will register the patient. If the patient is allocated to the 
intervention group, FoodforCare will be informed by the researcher. FoodforCare will take 
care of the delivering of the products and will have contact with the research assistants about 
the measurements. Before the start of the intervention, an individual intake will take place 
with the patient by FoodforCare. During this intake, the composition of the dishes will be 
tailored to the needs of the patient in terms of composition, diet, taste, flavor and portion size. 
These dishes will be delivered to the patients by FoodforCare every three days. Depending 
on the patient’s wishes, the partner or caregiver of the patient can receive the same dishes. 
In case the patient is allocated to the control group, the research assistants are informed to 
perform the measurements at home at the given time points.  
6.5 Withdrawal of individual subjects 
Specific criteria for withdrawal  
Subjects can end their participation in the study at any time for any reason if they wish to do 
so without any consequences. The investigator can decide to withdraw a subject from the 
study for urgent medical reasons.  
6.6 Replacement of individual subjects after withdrawal  
During the inclusion period, additional patients will be included to be able to achieve the 
necessary number of patients in case of withdrawal of patients during the study.  
6.7 Follow-up of subjects withdrawn from treatment  
When patients withdraw from the study after time point 3, these data may (if authorized by 
the patient) be used for analyses.  
6.8 Premature termination of the study  
Situations in which the study should be terminated prematurely are not expected. Moreover, 
the use of ‘usual care’ and the FoodforCare products bring no additional risk to the patients. 
Therefore, we do not expect a large number of adverse events in either group.  
 
 

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7. PATIENT SAFETY 
7.1 Section 10 WMO event  
In accordance to section 10, subsection 1, of the WMO, the investigator will inform the 
subjects and the reviewing accredited METC if anything occurs, on the basis of which it 
appears that the disadvantages of participation may be significantly greater than was 
foreseen in the research proposal. The study will be suspended pending further review by 
the accredited METC, except insofar as suspension would jeopardise the subjects’ health. 
The investigator will take care that all subjects are kept informed.  
7.2 AEs, SAEs and SUSARs  
7.2.1 Adverse events (AEs)  
Adverse events are defined as any undesirable experience occurring to a subject 
during the study, whether or not considered related to the Food for Care products. All 
adverse events reported spontaneously by the subject or observed by the investigator 
or his staff will be recorded.  
Our proposition will be to only register adverse events that have a possible causal 
relationship with the given food products. Examples of these events include 
gastrointestinal complaints and allergic reactions.  
7.2.2 Serious adverse events (SAEs)  
A serious adverse event is any untoward medical occurrence or effect that at any 
dose:  
- results in death;  
- is life threatening (at the time of the event);  
- requires hospitalisation or prolongation of existing inpatients’ hospitalisation;  
- results in persistent or significant disability or incapacity;  
- is a congenital anomaly or birth defect;  
- Any other important medical event that may not result in death, be life threatening, or 
require hospitalization, may be considered a serious adverse experience when, based 
upon appropriate medical judgement, the event may jeopardize the subject or may 
require an intervention to prevent one of the outcomes listed above.  
Our proposition will be to only register serious adverse events that have a possible 
causal relationship with the given food products. Examples of these events include 
gastrointestinal complaints and allergic reactions, which cause the above mentioned. 
7.2.3 Suspected unexpected serious adverse reactions (SUSARs)  
Not applicable for this study.  

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7.3 Follow-up of adverse events  
All AEs will be followed until they have abated, or until a stable situation has been reached. 
Depending on the event, follow-up may require additional tests or medical procedures as 
indicated, and/or referral to the general physician or a medical specialist. (S)AEs will be 
reported till the end of study.  
 

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8. STATISTICAL ANALYSIS 
8.1 Descriptive statistics 
Nominal and ordinal variables will be described using frequency tables, modus and medians. 
Continuous variables will be described in terms of means and confidence intervals or with 
medians and range, dependent on normality of the data.  
 
Data will be analyzed using IBM SPSS version 22 for descriptive and statistical analyses. All 
analyses will be performed according to the intention-to-treat principle. 
 
8.2 Primary study parameter(s) 
The primary study parameter is the change in hand grip strength between baseline and the 
end of the interventions, in percentages, compared to the control and the intervention group. 
This difference in percentages is a continue variable and will be compared by using the 
ANCOVA test.  
8.3 Secondary study parameter(s) 
The change in the other parameters for nutritional status between baseline and the end of 
het intervention will be compared between the control group and the intervention group. The 
continue variables such as, the change in BMI, quality of life, functional status and patient 
satisfaction will be analysed by a t-test. The ordinal variable such as, the MUST score and 
the PG-SGA will be analysed with a Mann-Whitney-U test. The difference in number of 
patients with a complication will be analysed by a Chi-square test. 
 
 

18 
 
9. ETHICAL CONSIDERATIONS 
9.1 Regulation statement  
This study will be directed according to the principles of the World Medical Association 
Declaration of Helsinki (64th WMA General Assembly, October 2013). Additionally, is it in 
agreement with the Medical Research Involving Human Subjects Act (WMO) and other 
guidelines, regulations and Acts.  
9.2 Recruitment and consent  
Patients will be recruited through the department of Medical Oncology at the Radboud 
University Medical Centre in Nijmegen. All patients admitted to this department en those who 
meet the inclusion criteria are asked to participate in the study. This request will be 
discussed with the patient by the nurse or one of the researchers. Additionally, patients will 
receive a patient information letter with further information about the study. When everything 
is clear and the patient is willing to participate in the study, the informed consent will be 
signed. When a patient is enrolled in the study, a personal number is assigned by one of the 
researchers. The researcher documents the patients’ data and the personal number in a 
designated protected document.  
9.3 Objection by minors or incapacitated subjects  
Not applicable.  
9.4 Compensation for injury  
There is a standard liability insurance available at the Radboud University Medical Centre for 
the study subjects. This is also written in the patient information letter. For the investigators 
there is also a liability insurance arranged at the Radboud University Medical Centre. In the 
proposal letter accompanying this protocol, we asked for release of a liability insurance for 
study subjects because this study includes usual nutritional care and meal service from 
FoodforCare which is already implemented in the medical centre. The patients will not be 
exposed to medical treatments during this study.  
9.5 Incentives  
Patients will not receive financial compensation for participating in the study. They will not 
have to pay additional hospital visits for this study and thus, they will have no additional 
travel costs or other costs. However, the intervention group will receive the meals and food 
products from FoodforCare for free. Due to the measurements that will be performed 3 
months after the intervention period, it will not be possible to continue with the FoodforCare 
meals after this period. Once the effectiveness of FoodforCare at Home has been 
demonstrated, it is likely that the meals will become available for regular use. 
 
 

19 
 
10. ADMINISTRATIVE ASPECTS, MONITORING AND PUBLICATION  
 
10.1 Handling and storage of data and documents  
All study documents will be stored in the investigator site file. The informed consent forms 
will also be stored in Epic. The researchers will enter all data into the database of Castor by 
means of the study number with their personal password. Only the researchers who are 
directly involved in the study have access to this program. The key to the codes will be 
stored in a secure digital environment, so the privacy and anonymity of the patients is 
ensured. Both the written data and the entered data in Castor will be stored for up to 15 
years after the study.  
 
10.2 Monitoring and Quality Assurance  
Looking at the directives of the NFU for on-site monitoring, the monitoring-class of the study 
is negligible. Minimum monitoring is indicated. The monitoring will be performed by an 
independent gastroenterologist according to the monitoring plan.  
 
    Monitor plan 
Monitor Frequency  
Once halfway the inclusion  
Patient flow  
Inclusion rate and drop-out 
percentage  
Trial Master File/ Investigator File  Presence and completeness of 
research file  
Informed Consent  
100%  
In-/exclusie Criteria  
First 3 subjects, thereafter 10%  
Source Data Verification  
10%  
 
10.3 Amendments  
Not applicable with first version of the research protocol.  
10.4 Annual progress report  
The investigator will submit a summary of the progress of the trial to the accredited METC in 
case the study takes longer than a year. In this report, information will be provided on the 
date of inclusion of the first subject, numbers of subjects included and numbers of subjects 
that have completed the trial, serious adverse events/ serious adverse reactions, other 
problems, and amendments.  
10.5 End of study report  
The investigator will notify the accredited METC of the end of the study within a period of 8 
weeks. The end of the study is defined as the last patient’s last visit. For this study, this will 
be after the last measurement moment of the last patient.  
In case the study is ended prematurely, the investigator will notify the accredited METC 
within 15 days, including the reasons for the premature termination. Within one year after the 
end of the study, the investigator/sponsor will submit a final study report with the results of 
the study, including any publications/abstracts of the study, to the accredited METC.  

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10.6 Public disclosure and publication policy  
After analyzing all data, the goal is to present the results on (inter)national conferences and 
to publish the results in an international journal, independently on positive or negative results 
of the study. This will be agreed with the sponsor in a contract.  
 

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11. STUCTURED RISK ANALYSIS 
 
11.1 Potential issues of concern  
A risk analysis, in respect to the cooperation contract between Maison van den Boer and the 
Radboud University Nijmegen Medical Centre, will be described in the Aanbiedingnotitie to 
the Board of Directors and will also be contracted. For example, the risk of financial loss will 
be clearly described in this contract. This letter will also disclose that FoodforCare has no 
influence on publishing (positive or negative) results.  
 
11.2 Synthesis  
As described previously, we expect that this meal concept will have no additional risk to the 
patients. In daily practice, the dishes of FoodforCare are widely offered to all patients in the 
hospital. Matters such as patient safety and hygiene will be respected. In light of these 
arguments, it does not seem necessary to us to give a structured risk analysis.  
 
 

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