A questionnaire-based survey to assess patient satisfaction, ease-of-learning, ease-of-use, injection site pain and overall patient satisfaction of the follitropin-alpha (Gonal-f) filled-by-mass (FbM) prefilled pen compared with other systems of gonadotrophin administration

Gonadotrophins are routinely used for follicular stimulation in ovarian induction (OI) and assisted reproduction techniques (ART). Follicle-stimulating hormone (FSH) and HMG (human menopausal gonadotrophin) are used during OI and ART to stimulate the growth and recruitment of immature follicles in the ovary [1, 2]. FSH is currently available in two preparations: urinary FSH (u-FSH) and recombinant FSH (r-FSH). HMG and u-FSH are extracted from the urine of postmenopausal women, whereas r-FSH, which became available in 1996, is produced using recombinant DNA technology.

Daily injections of recombinant peptides are required for several conditions such as growth hormone for growth deficiencies in children. Injections that are required on a long-term, regular basis must be quick, simple and as pain free as possible to ensure patients comply with treatment [3]. During treatment for OI and ART, gonadotrophins have to be injected daily for an average of 10 days and are often reconstituted from freeze-dried peptides. Traditionally, HMG has been administered as an intramuscular injection. However, the development of the higher purity FSH preparations has enabled subcutaneous injections to be used. Advances in FSH formulations have been accompanied by progress in the devices available for the delivery of the peptides. The subcutaneous administration systems that have evolved for r-FSH generally enable self-administration at home and have led to improvements in patient satisfaction and quality of life [4‐10].

It is well established that treatment outcomes can be affected by patient compliance, and that compliance is related to treatment choice and method of administration. For example, therapies that are easier to administer and cause less injection site pain are associated with higher rates of compliance than those that are difficult to administer and cause pain [4, 7, 10, 11]. It has been demonstrated previously that patients, who receive subcutaneous injections for IVF, reported experiencing less pain than those who receive intramuscular injections [12]. Moreover, it has been documented that patients can make errors in the reconstitution of freeze-dried peptides for self-administration at home, and pregnancy rates are higher in patients who prepare and administer injections correctly [10].

The follitropin-alpha (Gonal-f) filled-by mass (FbM) prefilled pen (Merck Serono SA, Geneva, Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany) is a ready-to-use disposable injection delivery device. The pen contains premixed follitropin alfa filled-by-mass, which provides more accurate and consistent dosing than r-FSH filled-by-bioassay [8]. Routine use of follitropin-alpha in ART was well accepted by patients participating in a German observational study; in addition, study patients required less training to use follitropin-alpha pens compared with vials or ampoules [13]. More importantly from a compliance point of view, patients preferred the prefilled pen compared with another loadable device (a reusable pen with loadable cartridges) [13]. Results from two other studies suggest that the follitropin-alpha prefilled pen had higher patient and nurse acceptance than the follitropin-beta pen (supplied in glass cartridges to be used with a pen injector; Puregon; Organon, Roseland, NJ, USA) [14]. Another survey found that more patients preferred the follitropin-alpha prefilled pen to the follitropin-beta cartridge pen or urofollitropin (Ferring Pharmaceuticals, Suffern, NY, USA) administered with a needle-free reconstitution device and conventional syringe. Additionally, patients stated that the ease of use, dosing mechanism and reduced potential for dosing errors were the factors that they found most important [15].

The current study was designed to evaluate overall patient satisfaction, ease of learning and use, and injection site pain associated with the follitropin-alpha (FbM) prefilled pen. A secondary comparison was made with other systems of gonadotrophin administration. The study—which involved over 650 patients treated at 23 Japanese fertility centres—was the largest study of patient preference to be performed in Japan.

The results from this questionnaire-based survey—which involved 663 women and was the largest of its type to be performed in Japan—show that the majority of patients found the follitropin-alpha pen easy to learn, to use and to administer with minimal pain experienced at the injection site. Higher overall patient satisfaction appeared to be associated with higher scores for ease of learning and use, as well as less pain at the injection site, although no direct correlation between these factors was found. Seventy-five percent (232/309) of patients who had experience of other treatments for infertility found the follitropin-alpha (FbM) prefilled pen the easiest product to use and almost all would recommend the use of the follitropin-alpha pen to other women. These results are comparable to those from two other studies reported in a single publication by Porter et al. [14]. The first was a 2-year observational study conducted in Germany, which found that patients favoured treatment with the follitropin-alpha (FbM) prefilled pen over the follitropin-beta pen due to faster preparation, greater confidence in dosing accuracy and the need for fewer dose adjustments [14]. In the second study, conducted in Australia, patients again favoured the follitropin-alpha (FbM) prefilled pen over the follitropin-beta pen for the same reasons. Additionally, patients experienced less injection site pain with the follitropin-alpha (FbM) prefilled pen than with the follitropin-beta pen [14]. A larger questionnaire-based study of 5328 patients undergoing ART in Germany reported that the routine use of the follitropin-alpha (FbM) prefilled pen was well accepted by patients [13]. In this study, patients found the follitropin-alpha (FbM) prefilled pen easier to learn to use than other injection methods and reported it as their preferred method of FSH administration [13].

The current study included an exploration of patients’ views on the different tools provided to teach them how to use the follitropin-alpha (FbM) prefilled pen. Surprisingly, web-based training was not widely utilised and was associated with lower overall satisfaction than the other training tools. Patients found hands-on demonstration by a doctor or nurse to be the most useful tool for learning how to use the follitropin-alpha (FbM) prefilled pen. When a healthcare professional demonstrates how to perform the injection, patients have the chance to ask any questions they may have on correct administration and what they should do if they encounter any problems. Asking a doctor or nurse can provide patients with the reassurance that they need to correctly administer the treatment at home by themselves. Interestingly, nurses have also reported very high levels of satisfaction with their experiences of teaching patients to use the follitropin-alpha pen [14].

One of the advantages of a ready-to-use device is that it reduces the chances of a reconstitution error occurring. The follitropin-alpha (FbM) prefilled pen lowers the possibility of both injection and dosing errors, which could potentially affect patient confidence in the device as well as the choice of device used in fertility programmes. Additionally, increased patient confidence, dosing consistency and dosing accuracy are key requirements for a drug delivery device to allow physicians to maximise the predictability of ovarian stimulation and success [10].

When questioned, over three quarters of the patients in the study who had previous experience of other gonadotrophin formulations and devices found the follitropin-alpha pen easier to use and reported less injection site pain than with other products. Of note, in a study of patients receiving human growth hormone injections, the five key delivery device attributes identified by patients were reliability, ease of use, lack of pain, safety in use and a small number of steps required for preparation [16]. The follitropin-alpha (FbM) prefilled pen encompasses all of these attributes. Also worthy of consideration is that the introduction of insulin self-injection pens for patients with diabetes led to an improvement in patient compliance and treatment outcomes, with patients reporting that they found injection pens less painful than syringes and needles [17‐22]. It is likely that the use of injection pens for infertility treatment that cause less injection site pain than conventional syringes will have a similar positive effect on compliance. It has also been demonstrated in many therapeutic areas that increasing patient information leads to increased patient satisfaction and adherence to treatment [23‐26].

Additionally, it has been suggested that the efficacy of ovarian stimulation regimens may improve with the use of injection pen devices compared with conventional syringes. This could be due to several factors such as increased adherence to treatment and also the correct administration and dosing of treatment. However, further evidence is required to support these claims [27‐29].

In summary, the follitropin-alpha (FbM) prefilled pen is an easy-to-use injection device and offers reduced injection site pain compared with conventional devices. A high level of overall patient satisfaction with the follitropin-alpha (FbM) prefilled pen was documented in this study involving 23 JISART-certified fertility centres in Japan. The results of this survey are in agreement with previous findings confirming the ease of learning and use of the pen in both previously untreated patients and patients with previous experience of other fertility treatments.