Response Rates for Patient-Reported Outcomes Using Web-Based Versus Paper Questionnaires: Comparison of Two Invitational Methods in Older Colorectal Cancer Patients

Background

Improving questionnaire response rates is an everlasting issue for research. Today, the Internet can easily be used to collect data quickly. However, collecting data on the Internet can lead to biased samples because not everyone is able to access or use the Internet. The older population, for example, is much less likely to use the Internet. The Patient-Reported Outcomes Following Initial Treatment and Long-Term Evaluation of Survivorship (PROFILES) registry offers a platform to collect Web-based and paper questionnaires and to try different measures to improve response rates.

Objective

In this study, our aim was to study the influence of two methods of invitation on the response rate. Our second aim was to examine the preference of questionnaire mode of administration (paper or Web-based) for the older patient in particular.

Methods

To test these two invitational methods, 3406 colorectal cancer patients between ages 18 and 85 years received an invitation containing an access code for the Web-based questionnaire. They could also request a paper questionnaire with an included reply card (paper-optional group). In contrast, 179 randomly selected colorectal cancer patients received a paper questionnaire with the invitation (paper-included group). They could also choose to fill out the Web-based questionnaire with the included access code.

Results

Response rates did not differ between the paper-optional and the paper-included groups (73.14%, 2491/3406 and 74.9%, 134/179, P=.57). In the paper-optional group, online response was significantly higher when compared to the paper-included group (41.23%, 1027/2491 vs 12.7%, 17/134, P<.001). The majority of online respondents responded after the first invitation (95.33%, 979/1027), which was significantly higher than the paper respondents (52.19%, 764/1464, P<.001). Respondents aged 70 years and older chose to fill out a paper questionnaire more often (71.0%, 677/954). In the oldest age group (≥80 years), 18.2% (61/336) of the respondents filled out a Web-based questionnaire.

Conclusions

The lack of difference in response rates between invitation modes implies that researchers can leave out a paper questionnaire at invitation without lowering response rates. It may be preferable not to include a paper questionnaire because more respondents then will fill out a Web-based questionnaire, which will lead to faster available data. However, due to respondent preference, it is not likely that paper questionnaires can be left out completely in the near future.     

Preclinical studies on the use of selective antibody-ricin conjugates in autologous bone marrow transplantation

Whole-ricin immunoconjugates were synthesized with the pan-T cell antibodies T101 and 3A1 and assayed in the presence of 0.1 mol/L lactose. Their toxicity for cell lines, peripheral blood T lymphocytes, and normal bone marrow progenitors was compared with that of whole ricin. In the presence of 0.1 mol/L lactose, normal cells and cell lines exhibited the following sensitivities to ricin: 8392 (human malignant B cell line) less than E rosette-positive lymphocytes less than bone marrow progenitors less than 8402 (human T ALL) less than CEM (human T ALL). Ricin sensitivities correlated with ricin binding as determined by immunofluorescence. In the presence of lactose, peripheral blood T cells were resistant to 0.1 nmol/L ricin, but a similar concentration of T101-ricin inhibited normal and malignant T colony formation by greater than 98%. 3A1-ricin was slightly less effective. At a conjugate concentration of 0.1 nmol/L, bone marrow progenitor colony formation was inhibited by 30% or less; T101-positive cells were at least tenfold more sensitive than normal progenitors. When mixtures of 10% CEM cells and marrow cells were incubated with T101-ricin, 95% of CEM colonies were killed, and 96% of marrow granulocyte/ macrophage progenitors survived. Some free ricin was released from immunotoxin-treated cells, producing minimal inhibition of protein synthesis or cell growth. We conclude that (a) normal blood cells and malignant cell lines exhibit varying degrees of ricin sensitivity in the presence of lactose; (b) T101-ricin is at least tenfold more toxic to T lymphocytes than to bone marrow progenitor cells and is effective in mixtures of normal and malignant cells; and (c) treatment of infiltrated marrow with anti-T cell immunotoxins should safely remove target T cells without excessively damaging normal progenitors or producing excessive free ricin. Anti-T cell, whole-ricin immunotoxins merit trials for autologous transplantation.     

Hemoglobin switching in sheep: a comparison of the erythropoietin- induced switch to HbC and the fetal to adult hemoglobin switch

Stimulation of sheep erythropoietic progenitor cells by erythropoietin (epo) has been studied with regard to its effect on the pattern of hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU- E- and CFU-E-derived colonies from fetuses either homozygous for HbA (AA) (homozygous also for the beta c gene responsible for HbC production) or HbB (BB) (lacking the beta c gene) indicated the following. Colonies derived from precursor cells from 51- and 89-day fetuses exhibited small but detectable increments of HbB synthesis with prolonged incubation in vitro. This response was not dependent on the epo concentration. Erythropoietic precursor cells from a 124-day BB fetus were already committed to HbB synthesis, since HbF production was replaced by HbB on successive days in vitro as erythroid colonies matured; this switch was not affected by varying the epo concentration. In contrast, progenitor cells from a 124-day AA fetus responded to higher doses of epo by forming colonies in which more HbC was made at the expense of both HbF and HbA. Erythropoietic stress did not result in induction of HbF in vivo or in erythroid colonies derived from CFU-E in young adult BB sheep, whereas our prior studies had shown induction of HbC synthesis under analogous conditions in colonies derived from young adult AA sheep. We conclude that the epo-induced HbF (or HbA) to HbC switch and the fetal to adult hemoglobin switch are regulated by different mechanisms.     

Pathogenesis of B cell lymphoma in a patient with AIDS

Lymphoma occurs at increased frequency in patients with the acquired immunodeficiency syndrome (AIDS). We studied, using serologic and molecular techniques, one such lymphoma for (a) evidence of infection with human T lymphotropic virus, type III (HTLV-III), and Epstein-Barr virus (EBV), (b) monoclonal rearrangement of immunoglobulin and T cell receptor genes, and (c) rearrangement of the c-myc oncogene. Immunoglobulin and T cell receptor gene studies demonstrated that the tumor was of monoclonal B cell origin. Similar to cases of Burkitt's lymphoma unrelated to AIDS, there were DNA sequences in the lymphoma that hybridized to EBV-specific probes and demonstrated evidence of c- myc rearrangement. HTLV-III sequences were not detected in the malignant B cells. The pathogenesis of some B cell neoplasms in patients with the syndrome may involve transformation by EBV and deregulation of oncogene expression without direct infection of the malignant B cells by HTLV-III.     

Vaccination and autoimmune disease: what is the evidence?

As many as one in 20 people in Europe and North America have some form of autoimmune disease. These diseases arise in genetically predisposed individuals but require an environmental trigger. Of the many potential environmental factors, infections are the most likely cause. Microbial antigens can induce cross-reactive immune responses against self-antigens, whereas infections can non-specifically enhance their presentation to the immune system. The immune system uses fail-safe mechanisms to suppress infection-associated tissue damage and thus limits autoimmune responses. The association between infection and autoimmune disease has, however, stimulated a debate as to whether such diseases might also be triggered by vaccines. Indeed there are numerous claims and counter claims relating to such a risk. Here we review the mechanisms involved in the induction of autoimmunity and assess the implications for vaccination in human beings.     

Altered expression of transforming growth factor betas during urethral and bulbourethral gland tumor progression in transgenic mice carrying the androgen-responsive C3(1) 5' flanking region fused to SV40 large T antigen

We demonstrate that targeted expression of SV40 large T antigen (TAg) to the urethral (periurethral) and bulbourethral gland epithelium leads to adenocarcinoma formation in these tissues after 7 months of age, which are extremely rare sites for spontaneous tumor formation in humans. The development of proliferative lesions in the urethral gland predictably follows a temporal course of progression with approximately one third of male animals developing urethral tumors by 1 year of age. Tumor progression in these organs correlates to the level of TAg and p53 expression. Immunoprecipitation confirmed that SV40 TAg protein was bound to p53 and Rb p110 in vivo. Expression of transforming growth factor beta (TGFbetas) was evaluated during tumor progression of urethral gland carcinomas. Elevations of intracellular and extracellular TGFbeta1 and extracellular TGFbeta3 were found in preneoplastic and neoplastic lesions, suggesting that increased TGFbetas may augment tumor growth. c-Met expression showed a tendency for increased expression in the urethral gland carcinomas. We speculate that the directed expression of SV40 TAg by the hormone responsive C3(1) gene and subsequent tumor formation in these organs is influenced by androgens, since these tissues and carcinomas express androgen receptor (AR) and arise only in male transgenic mice. Several cell lines established from the urethral carcinomas were also shown to express AR, but are not androgen dependent in culture. To our knowledge, this is the first transgenic animal model for urethral and bulbourethral carcinomas. This transgenic mouse model and the cell lines derived from it may provide a unique opportunity for dissecting molecular mechanisms involved in the tumorigenesis of these organs which otherwise rarely develop cancer.